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ORGANIC REACTION MECHANISMS ⋅ 2016
ORGANIC REACTION
MECHANISMS ⋅ 2016
An annual survey covering the literature
dated January to December 2016
Edited by
A. C. Knipe
University of Ulster
Northern Ireland
This edition first published 2020
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Contributors
K. K. BANERJI Department of Chemistry, J. N. V. University,

Jodhpur, India
C. T. BEDFORD Department of Chemistry, University College

London, London, UK
M. L. BIRSA Faculty of Chemistry, ‘Al. I. Cuza’ University of Iasi,
Iasi, Romania
J. M. COXON Department of Chemistry, University of Canterbury,
Christchurch, New Zealand
M. R. CRAMPTON Department of Chemistry, University of Durham,

Durham, UK
N. DENNIS 3 Camphor Laurel Court, Stretton, Queensland,

Australia
D. A. KLUMPP Department of Chemistry, Northern Illinois

University, DeKalb, IL, USA
P. KOČOVSKÝ Department of Organic Chemistry, Charles

University, Czech Republic and Department of
Organic Chemistry, Stockholm University, Sweden
M. G. MOLONEY Chemistry Research Laboratory, Department of
Chemistry, University of Oxford, Oxford, UK
B. A. MURRAY Department of Science, Technological University of
Dublin (TU Dublin), Dublin, Ireland
K. C. WESTAWAY Department of Chemistry and Biochemistry,

Laurentian University, Sudbury, Ontario, Canada
v
Preface
The present volume, the 52nd in the series, surveys research on organic reaction
mechanisms described in the available literature dated 2016. In order to limit the size
of the volume, it is necessary to exclude or restrict overlap with other publications
which review specialist areas (e.g. photochemical reactions, biosynthesis, enzymology,
electrochemistry, organometallic chemistry, surface chemistry, and heterogeneous
catalysis). In order to minimize duplication, while ensuring a comprehensive coverage,
the editor conducts a survey of all relevant literature and allocates publications to
appropriate chapters. While a particular reference may be allocated to more than one
chapter, it is assumed that readers will be aware of the alternative chapters to which a
borderline topic of interest may have been preferentially assigned.
All the chapters have been written by the members of a team of experienced ORM
contributors who have submitted authoritative reviews over many years. We are natu-
rally pleased to benefit from such commitment and consequent awareness of developing
trends in the title area. Particularly noteworthy in recent years has been a major impact
on directed organic synthesis through mechanistic studies which enable optimization of
ligand design for highly selective transition metal catalysts.
In view of the considerable interest in the application of stereoselective reactions to
organic synthesis, we now provide indication, in the margin, of reactions which occur
with significant diastereomeric or enantiomeric excess (de or ee).
Although every effort was made to reduce the delay between the title year and the pub-
lication date, circumstances beyond the editor’s control again resulted in the late arrival
of a substantial chapter which made it impossible to regain our optimum production
schedule.
Steps have been taken to reduce the knock-on effect of this occurrence.
I wish to thank the staff of John Wiley & Sons and our expert contributors for their
efforts to ensure that the review standards of this series are sustained.
A.C.K.
vii
Contents
1. Reactions of Aldehydes and Ketones and Their Derivatives

by B. A. Murray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2. Reactions of Carboxylic, Phosphoric, and Sulfonic Acids and their
Derivatives
by C. T. Bedford . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3. Oxidation and Reduction
by K. K. Banerji . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4. Carbenes and Nitrenes
by M. G. Moloney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
5. Aromatic Substitution
by M. R. Crampton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
6. Carbocations
by D. A. Klumpp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
7. Nucleophilic Aliphatic Substitution
by K. C. Westaway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
8. Carbanions and Electrophilic Aliphatic Substitution
by M. L. Birsa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
9. Elimination Reactions
by M. L. Birsa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
10. Addition Reactions: Polar Addition
by P. Kočovský . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
11. Addition Reactions: Cycloaddition
by N. Dennis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661
12. Molecular Rearrangements
by J. M. Coxon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 697
Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 833
ix
CHAPTER 1
Reactions of Aldehydes and Ketones and Their Derivatives
B. A. Murray
Department of Science, Technological University of Dublin (TU Dublin), Dublin,
Ireland
Formation and Reactions of Acetals and Related Species . . . . . . . . . . . . . . 2

Reactions of Glucosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Reactions of Ketenes and Related Cumulenes . . . . . . . . . . . . . . . . . . . . . 7
Formation and Reactions of Nitrogen Derivatives . . . . . . . . . . . . . . . . . . . 8
Imines: Synthesis, and General and Iminium Chemistry . . . . . . . . . . . . . 8
Mannich, Mannich-type, and Nitro-Mannich Reactions . . . . . . . . . . . . . 10
Other ‘Name’ Reactions of Imines . . . . . . . . . . . . . . . . . . . . . . . . 14
Stereoselective Hydrogenation of Imines, and Other Reductive Processes . . . . 15
Stereoselective Allyl-, Aryl-, Alkenyl-, and Alkynyl-ations of Imines . . . . . . 17
Other Stereoselective Reactions of Imines . . . . . . . . . . . . . . . . . . . . 18
Other Reactions of Imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Oximes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Hydrazones and Related Species . . . . . . . . . . . . . . . . . . . . . . . . . 24
C–C Bond Formation and Fission: Aldol and Related Reactions . . . . . . . . . . 27
Reviews of Aldols, and General Reviews of Asymmetric Catalysis . . . . . . . 27
Asymmetric Aldols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
The Mukaiyama Aldol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
The Morita–Baylis–Hillman Reaction . . . . . . . . . . . . . . . . . . . . . . 31
Other Aldol-type Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Allylation and Related Reactions . . . . . . . . . . . . . . . . . . . . . . . . . 33
Alkynylations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
The Benzoin and Stetter Reactions . . . . . . . . . . . . . . . . . . . . . . . . 36
The Michael Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Miscellaneous Condensations . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Other Addition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Addition of Organozincs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Arylations, and Addition of Other Organometallics, Including Grignards . . . . 42
The Wittig and Other Olefinations . . . . . . . . . . . . . . . . . . . . . . . . 43
Hydrosilylation, Hydrophosphonylation, Hydroboration, and Hydroacylation . . 45
Formation of Cyanohydrins, Cyanosilylation, and other Cyanations . . . . . . . 47
𝛼-Aminations and Related Reactions . . . . . . . . . . . . . . . . . . . . . . . 48
Enolization, Reactions of Enolates, and Related Reactions . . . . . . . . . . . . . . 48
𝛼-Halogenation, 𝛼-Alkylation, and Other 𝛼-Substitutions . . . . . . . . . . . . 50
Oxidation and Reduction of Carbonyl Compounds . . . . . . . . . . . . . . . . . . 51
Oxidation of Aldehydes to Acids . . . . . . . . . . . . . . . . . . . . . . . . . 51
Other Oxidations and Oxidative Processes . . . . . . . . . . . . . . . . . . . . 52
Reduction Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Organic Reaction Mechanisms 2016, First Edition. Edited by A. C. Knipe.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
1
2 Organic Reaction Mechanisms 2016
Miscellaneous Cyclizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Other Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Formation and Reactions of Acetals and Related Species

𝛾,𝛿-Unsaturated aldehydes (e.g. 1) undergo endo-selective Prins bicyclization with
aldehydes to give dioxabicyclo[2.2.2]octanes (2) in high de and ee. Glyoxylic esters
work well (i.e. R = COCO2 Et), with induction by a chiral BINOL-derived N-triflyl-
phosphoramide at ambient temperature.1
(S) O (S)
R–CHO
O (R)
O
R
(1) (2)
Organocatalytic enantioselective routes to two classes of cyclic acetals have been

described. Chiral 5,5-fused tetrahydrofurobenzofurans (bearing two stereocentres)
and 5,6-bridged methanobenzodioxepines (bearing three) have been prepared from
hydroxyarenes and 𝛾-keto-enals. Using diphenylprolinol TMS ether as catalyst, very
low loadings are required for these very efficient iminium catalyses. The pathways have
been probed using DFT.2
ee
Treatment of 𝛼-diazo-𝛽-ketoesters (3) with cyclic ketones, lactones, or carbonates

(4; X, Y = CH2 ,O n = 0–3) yields spiro ketals, orthoesters, or orthocarbonates (5).
The key first step of diazo decomposition requires a catalyst combination of 1,10-
phenanthroline and a ruthenium salt, [CpRu(MeCN)3 ]+ [BAr4 ]− , where Ar = 3,5-
bis(trifluoromethyl)phenyl.3
O R2
O
O R2
R1O O
+ X Y
R1O O O Y
N2 ( )n X
( )n
(3) (4) (5)
Spiroacetalization of two enol ethers (6; n = 1 or 2) has been the subject of a QM/
MM study which compares two catalysts: a chiral phosphoric acid and a chiral imi-
dodiphosphoric acid with a much more confined ‘active site’. For the first catalyst (a
BINAP–phosphoric acid with buttressing anthracenes), the ee is only 1% for the forma-
tion of the 5,5-spiro-system (7; n = 1): the substrate is small, fits inside, and induction is
negligible. In the second catalyst, the ee goes up to 92%, reflecting a confinement effect.
The 6,6-reaction (7; n = 2) shows a slightly higher ee of 95% for the second catalyst.4
ee
1 Reactions of Aldehydes and Ketones and Their Derivatives 3
O ( )n
O ( )n
OH ( )n O
( )n
(6) (7)
Vinyl propynyl acetals (8) can be rearranged to yield catechol ethers (9) using gold(I)
in 1,2-dichloroethane (DCE) at 25 ∘ C. Alkyne activation triggers nucleophilic addition
of acetal oxygen, setting up an equilibrium mixture of oxonium ions of similar stability.
These can be considered as ‘kinetically self-sorted’ by the next step: highly exothermic
cyclization. Computations support this view, as the barriers between the oxonium ions
are low, so the system can be considered as an example of dynamic covalent chemistry
(DCC), where the fast equilibration acts like an ‘error-checking’ process. The alkene
‘linker’ in the substrate can be replaced by an aromatic (or heteroaromatic), resulting in
naphthyl analogues, etc. Syntheses of the substrate acetals (8) are also described.5
PMP
OR
OR O O
AuI/AgNTf2
OMe
OMe Cl–CH2–CH2–Cl
OMe
(8) (9) (10) OH
Enantiomeric acetals (10) show a surprising difference under reductive cleavage by

diisobutylaluminium hydride. The 𝛼-acetal (PMP behind) is converted to a PMB ether,
while the 𝛽-acetal is resistant [but can be opened with Na(CN)BH3 /TMS–Cl].6
Substituted benzothiophenes have been prepared from substituted thiophenoxy-
acetaldehyde diethyl acetals, X–C6 H4 –S–CH2 –CH(OEt)2 , in the presence of poly-
phosphoric acid. The mechanisms have been probed by way of kinetic and computational
studies.7
Proline catalyses reaction of dihydroxyacetone isopropylidene acetal (11) with enan-
tiopure 𝛼-silyloxy aldehyde (12) to give a single isomer (13) cross-aldol product in
91% yield in a substantially aqueous medium at ambient temperature. This result has
now been investigated by NMR spectroscopy, monitoring individual steps, allowing
the role of water to be better understood. It is found that proline ‘protects’ aldehyde
(12) as an oxazolidinone, but this means that the catalyst is effectively ‘trapped’ by
aldehyde (12) … , but the high water content helps avoid this. Water also mediates
prolyl group exchanges, and opposes dehydration of the aldol. NMR also allowed detec-
tion of a ‘wanted’ intermediate, an enamine of the adduct (14). The authors count two
unfavourable effects of water countervailed by four favourable ones.8
de
BINOL-based trifluoromethyl aryl ketones (15; R = H or CH2 OMe) act as fluores-

cence sensors for 1,2-diamines in organic solvents, with a dramatic increase at 375 nm
and a decrease at 500 nm. Little effect is seen with other diamines (or monoamines), so
O
O O OH
3S 5S CO2H
OTBDPS 4R N OH
O O (12) O O OTBDPS
proline O O OTBDPS
DMSO/H2O/r.t.
(11) (13) (14)
diketones (15) can act as highly selective ratiometric sensors for 1,2-diamines, especially
ethylenediamine. UV and NMR studies suggest formation of a hemiaminal (16) at the
electron-deficient carbonyl, with stabilization by hydrogen bonding from the second
nitrogen. Such a non-covalent interaction is absent for a monoamine, and would be
poorly optimized for a longer diamine. Job plots for the fluorescence interaction suggest
an unexpected 1:4 stoichiometry (rather than 1:2), indicating that the phenolic oxygens
can also hydrogen-bond 1,2-diamines.9
OH
R1 H
NR22
(17)
O
CF3
HO H
H C
NH2
O R1 NR22
OR
(19)
OR Ar N
F 3C
(16)
O O NR22
CF3
R1 NR22 R1
(15) O (E-18) (Z-18)
Alkynylhemiaminals (17) can be prepared from propargyl aldehydes, or oxidatively

from propargyl alcohols. The Meyer–Schuster reaction was then studied for stereose-
lective synthesis of 𝛽-enaminones (18). Catalysed by Brønsted acids, the selectivity of
this rearrangement has now been found to be very simply tuneable: benzoic acid gives
(Z-18), while tosic acid gives (E-18). The key step is the protonation of the allenol inter-
mediate (19). The mechanism is supported by 18 O-labelling experiments.10
de
2-Substituted 2H-chromenes (20) have been prepared via aniline-catalysed nucle-
ophilic attack on ortho-hydroxycinnamaldehydes, via N,O-acetals. The cyclization–
substitution cascade accommodates a broad range of nucleophiles including indoles,
pyrroles, phenols, and silyl enol ethers.11
MeO Ph
S
MeO
O Nu S
MeO Ph
(20) (21)
Enantioselective aminomethylation of 𝛼,𝛽-unsaturated aldehydes, R–CH=CHCHO,

by an N,O-acetal, Bn2 N–CH2 –OMe, to give a 𝛽 2 -amino ester, R–CH2 –*CH(CH2 NBn2 )
–CO2 Me, has been reported to occur under NHC/Brønsted acid dual catalysis, but a
theoretical investigation has surprisingly uncovered a specific role for the Brønsted base,
refining the mechanism to an NHC/Brønsted acid/Brønsted base multi-catalysis.12
ee
For a reactivity scale for N,O-acetals, see the ‘𝛼-Aminations’ section.

A bifunctional tertiary-amide squaramide catalyst allows highly enantioselective addi-
tion of methyl thioglycolate (HS–CH2 CO2 Me) to N-Boc aldimines, giving a range of
chiral N,S-acetals.13
ee
3,4,5-Trimethoxybenzaldehyde undergoes reversible dithioacetal formation (21) with

2-phenylethanethiol under mild acidic conditions. Subsequent exchange with other thi-
ols and disulfides suggests that the methodology may be useful in DCC.14
Multi-substituted furans (22) have been prepared from 𝛽-chlorovinyl dithianes (23),
using a cyclization with aromatic aldehydes under mild metal-free conditions. The tactic
involves the dithiane inducing a cycloaddition–aromatization sequence. The strong
base dehydrochlorinates (23), giving an allenyldithiane donor (separately isolable),
which – on reaction with aldehyde – yields a spirodihydrofuran (24). Protonation then
drives aromatization. The disulfide side-chain of the product (22) is easily removed, if
desired, using Raney nickel/ethanol reflux.15
HS
Ar2 O
O Ar2-CHO S
Ar2 S S
1. tBuOK;
Cl S
Ar1 S
2. HCl
Ar1 workup Ar1 H
(22) (23) (24)
Reactions of Glucosides
Transition-metal catalysis of glycosylation is the subject of a comprehensive review (196
references), including recent advances in stereoselective syntheses of O-, N-, C-, and S-
glycosides.16 The use of a sulfoxide as a glycosyl donor is 30 years old, and their initial
de
use as anomeric leaving groups has expanded into other roles in glycosylations. A review
examines the mechanistic aspects (55 references).17 Chemical derivatization of sulfated
de
glycosaminoglycans has been reviewed (220 references).18
The origin of 𝛼-(1,2-cis) selectivity in galactosyl and galactosaminyl donors with a

di-tert-butylsilylene (DTBS) group has been probed by experiment and computation.
The major factors found were (i) generation of an oxocarbenium ion and through-space
stabilization thereof by electron donation from O(4) and O(6), (ii) a 4,6-O-silylene
structure, and (iii) steric hindrance by bulky substituents.19
de
Glycosyl methanesulfonates undergo regio- and stereo-selective couplings with par-

tially protected pyranoside and furanoside acceptors. In a notable example, a somewhat
𝛼-selective process (2:1) is switched to being 𝛽-selective (10:1) in the presence of a
rigid biarylborinic acid (25). Reaction progress kinetic analysis and EXSY (exchange
spectroscopy) NMR have been used to probe uncatalysed and catalysed mechanisms.20
de
O O D
O
chiral
B D O
OH HO BINAP–
phosphoric
R
R
acid
R R
(25) (26) (27)
Anomeric sulfonium ions can act as glycosyl donors for stereoselective installation of
1,2-cis glycosides, but their mechanism is not well characterized. Derivatization, NMR
kinetics, and computation have examined non-sulfur analogues to help pin down the role
of sulfur. It appears that a sulfonium ion is formed as a trans-decalin ring system that can
undergo glycosylation through a bimolecular mechanism, with the sulfonium ion form-
ing a hydrogen-bonded complex with the acceptor that undergoes SN 2-like glycosylation
to give 𝛼-anomeric product.21
de
A popular urea organocatalyst, N,N’-bis[3,5-bis(trifluoromethyl)phenyl]urea, has been

employed in stereoselective Koenigs–Knorr glycosylations, avoiding methods involving
heavy metals. For dealing with the low 𝛼-selectivity found with perbenzylated donors,
addition of tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) greatly improved results.
The effect of both additives has been ascribed in part to hydrogen-bonding effects, sup-
ported by 1 H NMR studies.22
Nucleophile-directed stereocontrol over glycosylations has been developed using
geminally difluorinated nucleophiles such as HO–CH2 –CF2 –CH2 –NBnCbz. The
two fluorines lower the oxygen nucleophilicity and reverse the stereoselectivity to
preferentially form cis-glycosides.23
de
1-O-Acetylfuranoses and pyranose 1,2-orthoesters act as excellent glycosyl donors

when activated by a gold(III)/phenylacetylene relay, with a preference for 1,2-trans-
glycoside products.24
de
Iodonium ions, generated from N-iodosuccinimide and triflic acid, promote glycosy-
lation of disarmed glycosyl bromide, avoiding the need for heavy-metal salts.25
A new stereoselective synthesis of 𝛽-mannopyranosides employs anomeric O-
alkylation of mannopyranoside-derived lactols, exploiting a kinetic anomeric effect and
chelation by caesium.26
Radicamine A and B are azasugars, and their fluorinated derivatives have been
prepared from a d-arabinose-derived cyclic nitrone. Their ability to inhibit glycosidases
has been tested.27
Stereoselectivity of chiral phosphoric acid-catalysed spiroketalization of deuterium-
labelled cyclic enol ethers (e.g. 26 → 27) has been probed by experiment and
computation. Long-lived oxocarbenium intermediates were ruled out, and Hammett
analysis of the kinetics revealed accumulation of positive charge at the transition
state. Secondary kinetic isotope effects (KIEs) are reported. Computations, including
de
molecular dynamic simulations, suggest an asynchronous concerted route with a TS
lifetime of about 500 fs.28
ee
Reactive boron species are useful in sensing applications of d-fructose. A kinetic

study examined phenylboronic acid and its 2-methyl and 2-isopropyl derivatives, plus
1-hydroxy-3H-2,1-benzoxaborole. Both boronic acids and boronate ions were reactive
towards d-fructose, the latter more so.29
Oxidative NHC catalysis has been used for regio- and chemo-selective functionaliza-
tion of carbohydrates.30
The valuable feedstock, furfural (furan-2-carboxaldehyde), can be generated from
xylose under hydrothermal conditions. A DFT study identifies xylulose as a likely
intermediate, with water lowering the TS barrier by 12.8 kJ mol−1 compared to the
gas phase. Explicit participation of a water molecule results in the replacement of
four-membered transition states for several steps with less-strained six-membered
ones.31
DFT has been used to study the iridium-catalysed chemoselective C(1)–O reduction
of glucose with silene.32
Reactions of Ketenes and Related Cumulenes
The first ketene N,S-acetal was reported in 1956, and their chemistry is the subject of a
comprehensive review (234 references).33
Several candidates for prebiotic interstellar chemistry have been examined. Keten-
imine and methyleneimine, identified in interstellar space, have been proposed as
precursors of prebiotic species. Second-order Moller–Plesset perturbation theory
(MP2) has been employed to investigate their reactivity, with pericyclic reactions giving
rise to five-membered cyclic carbene intermediates, leading – through subsequent
hydrogen transfers – to pyrazoles and imidazoles.34 In similar studies, the cycload-
dition of ketenimine with various unsaturated compounds shows that five-membered
cyclic carbenes appear achievable with acetonitrile, leading to 3-methylpyrazole
and 2-methylimidazole,35 while reaction with hydrogen cyanide can give pyrazole and
imidazole via similar processes,36 and reaction with ethyne or ethene gives pyrroles or
pyrrolines, respectively.37
O-Silyl cyanohydrins (28) can be converted to silyloxy-N-silylketenimines (29) in situ,
but these in turn convert to 𝛼-ketoamides (30) on brief exposure to air. A 3-imino-1,2-
dioxetane (31), formed spontaneously by triplet oxygen, is postulated to explain the
facile oxidation of (29). The cases reported involve R being an aryl or vinyl substituent.38
OTBS O
TBSO H TIPS–Cl air H
N
R ambient R TIPS
R CN NaHDMS C
−80 °C N TIPS O
(28) (29) (30)
O
O O
R
TBSO N TIPS
NTs
(31) (32) R
𝛼-Addition of aldehydes (e.g. Pr–CHO) across allenamides, H2 C=C=CH–N(R)Ts,

gives aldehyde–enamine derivatives (32).39 Catalysis is by gold(I) and a diarylprolinol
silyl ether: the former activates the allenamide, and the latter the aldehyde. Such catalysts
also render the reaction enantioselective.40
Formation and Reactions of Nitrogen Derivatives

Imines: Synthesis, and General and Iminium Chemistry
A ‘new’ synthesis of N-sulfonyl arylaldimines, Ar–CH=N–SO2 R, has been reported41a
… it having ‘failed’ in 1960.41b Simply heating an arylaldehyde with a sulfinyliso-
cyanate, RO2 S–N=C=O (neat, or in a solvent), gives the sulfinylimine, with loss of CO2
driving the process. Neither catalyst nor additive is required. For the example of para-
tolualdehyde and tosylisocyanate, refluxing in DCE at 90 ∘ C for 40 min delivers 93%
yield (after recrystallization). 2 + 2-Cycloaddition via a cyclic carbonate-type interme-
diate (33) is discussed.41a
O
O X
Ar
N
N
Ar SO2R
(33) (34)
The kinetics of condensation of 4-methoxybenzaldehyde with 2-aminobenzamide

have been measured using formic acid as both catalyst and solvent.42
Benzimidazoles (34; X = NH) are easily prepared by condensation of ortho-phenyl-
enediamine with aryl aldehydes using TiCl3 OTf in ethanol at ambient temperature. Sim-
ilarly, ortho-aminophenol yields benzoxazoles (34; X = O).43
A dehydrogenative cross-coupling strategy converts 1,2,3,4-tetrahydroquinolines
(35) into 3-benzylquinolines (36), using an aldehyde, a simple ruthenium catalyst,
and oxygen. The transformation is equivalent to 𝛽-benzylation of quinolines. Control
experiments helped establish the mechanism: radicals were ruled out as scavengers
had no effect, and quinoline would not react with benzaldehydes (or benzyl alcohols).
Critically, enamine (37) would, identifying it as an intermediate, and showing that
reaction with benzaldehyde precedes the second dehydrogenation of the ring.44
R2–CHO
R2
R1 [RuCl2(p-cymene)]2 R1 R1
N O2/120 °C N N
H H
(35) (36) (37)
Trifluoromethyl ketimines, R–C(CF3 )=N–CH2 –Ar, have been enantioselectively iso-

merized via symmetric proton transfer, using a chiral cinchonium betaine catalyst. The
tautomeric products, R–CH(CF3 )–N=CHAr, afford access to optically active trifluo-
romethylated amines,45 with the overall process mimicking transamination.
ee
2-Methoxyimidoyl-oxiranes (38) have been prepared diastereoselectively by trapping
𝛼-phosphonyloxy enolates with aldehydes (Ar2 –CHO). Dimethyl phosphite initiates
coupling of an 𝛼-keto N-tert-butylsulfinyl imidate, Ar1 –CO–C(OMe)=NS(O)–But ,
initiating a cascade sequence. A [1,2]-phospha-Brook rearrangement follows, to give
the 𝛼-phosphonyloxy enolate. This Darzens-type process for preparing epoxides via
𝛼-phosphonyloxy enolates and aldehydes can be viewed as the oxygen analogue of the
corresponding reaction with aldimines to give aziridines.46
de
R1 CO2H
−
But O N O
S Ar1 O Ar 2
NH
N HO R2
H
OMe +
N
H
(38) (39)
Novel chiral pyridoxamines catalyse enantioselective transamination. The biometric

process converts 𝛼-keto acids (R1 –CO–CO2 H) to 𝛼-amino acids in up to 87% ee, using
amino-diphenyl acetic acid [2,2-diphenylglycine, Ph2 C(NH2 )CO2 H] as amine donor,
driven by loss of CO2 , with benzophenone as the other by-product, in aqueous methanol
at ambient temperature. The pyridoxamine catalyst is proposed to condense with the
𝛼-keto acid to give a ketimine which undergoes asymmetric 1,3-proton transfer tau-
tomerization to an aldimine. Hydrolysis then gives the 𝛼-amino acid, with a pyridoxal
as by-product. The proton transfer may involve a pyridinium-stabilized azaallyl anion
(39).47
ee
Copper(I) coupling of a ketone, R1 –CO–CH2 –CH2 –(CH2 )n –Cl (n = 1, 2), a primary

amine, R2 –NH2 , and a terminal alkyne, H–C≡C–R3 , yields 2-alkynyl N-heterocycles
R3
( )n
R1 N+
( )n −
R1 N X
R2
R2
(40) (41)
(40) in up to 98% yield, via in situ generation of a cyclic ketiminium species (41), which
is more reactive towards alkynylation than acyclic analogues.48
A salicylaldehyde derivative has been used in an oxidative kinetic resolution of
indolines with a chiral phosphoric acid catalyst. A self-redox process of the iminium
intermediate is described.49
ee
A DFT study has examined Jorgensen–Hayashi-type amines as catalysts of iminium-

type additions of 𝛽-keto-sulfoxides and -sulfones to enals. High enantio- and diastereo-
de
selectivity is observed for the sulfoxides, but the de drops for the sulfones.50
ee
Phosphate-mediated Pictet–Spengler cyclization has been studied by DFT and

ab initio methods in vacuo and in acetonitrile. Examining the reactions of phenethy-
lamine and its 3-hydroxy derivative with formaldehyde to give the corresponding
tetrahydroisoquinoline was, with lower barriers in solution.51
Mannich, Mannich-type, and Nitro-Mannich Reactions

Free fluorinated amide enolates (42; R = H, alkyl, aryl) derived from 3-fluoroindolin-2
-one have been generated in situ by lithium-promoted detrifluoroacetylation of an
𝛼-fluoro-𝛽-ketoamide hydrate (43). Subsequent Mannich additions with sulfiny-
laldimines bearing fluoroalkyl groups are very clean, with up to 97% yield and >96%
de of protected amine (44). Both steps take 5 min at 0 ∘ C. Deprotection then gives an
𝛼-fluoro-𝛽-(fluoroalkyl)-𝛽-aminoindolin-2-one.52
de
HO CF Rf
HO
3 F BuOtS-HN
F LiBr SOBut F
O−
Rf
DIPEA O
O N
N R N
R R
(43) (42) (44)
The first organocatalysed direct Mannich reaction of unactivated 𝛼-styrylacetates

adds them to N-tosyl benzaldimines to give N-tosyl 𝛽-amino esters. The cinchona

de
alkaloid–urea catalyst employed gives yields/de/ee up to 84/92/97%.53

ee
𝛼-Fluoroketones undergo Mannich reaction with N-tert-butylsulfinylimines in up to

98% de.54

de
A diastereoselective Mannich reaction of an aromatic aldimine and a phenyl oxazoli-

dine promoted by TiCl4 /R3 N stops at the titanium enolate stage unless a proton source
is added. The process has been examined by low-temperature NMR, with acetic acid
proving the best additive. The protocol, run slowly at −50 to −40 ∘ C, has to strike a fine
balance, as direct protonation of the enolate reverts it to the reactant.55
de
A zinc–proline–phenol catalyst gives high de and ee in Mannich reactions of

𝛼-branched ketones with N-Boc aldimines, giving 𝛽-amino ketones with an all-carbon

de
quaternary stereocentre in the 𝛼-position.56

ee
A diastereo- and enantio-selective Mannich addition/cyclization reaction of 𝛼-

substituted isocyanoacetate ester pronucleophiles with ketimines employs a binary
catalyst system of silver acetate and a cinchona-derived amino phosphine. An X-ray
crystal structure of the amino phosphine/silver acetate complex, as well as 1 H and 31 P
NMR studies, helps support a mechanistic proposal. The product imidazolines can be

de
hydrolysed to give fully substituted 𝛼,𝛽-diamino acids.57

ee
𝛼,𝛽-Tetrasubstituted imidazolines (45) are prepared from 𝛼-substituted 𝛼-isocyano-

acetates [R4 –CH(CO2 R5 )–N+ ≡C− ] and ketimines (R1 R2 C=N–R3 ) via a Mannich
reaction catalysed by a cinchona alkaloid/nickel(II)/Cs2 CO3 combination: typical

de
yields/de/ee are in the 90s.58

ee
O
R3 O
N N F
NHBoc R1
R2 CO2R5 SR2
R1 R4 I
C6H4-para-R
(45) (46) (47)
Functionalized propargylic amines have been prepared in high de and ee via a syn-
selective Mannich reaction of enolizable aldehydes and C-alkynyl imines, catalysed by
de
proline and an achiral aminal/urea co-catalyst.59

ee
The enantioselective direct Mannich addition of ethyl acetoacetate to arylideneureas,

Ar–CH=NCONH2 , has been used to explore non-covalent organocatalysis by networks
ee
of cooperative hydrogen bonds.60
𝛼-Fluoro aromatic ketones undergo zinc-catalysed Mannich reactions with N-Boc-

de
benzaldimines to give protected 𝛽-fluoroamines (e.g. 46) with ee/de up to 99/95%.61

ee
A syn-selective direct Mannich addition uses 𝛼-iodo thioesters (47) and sulfinyl imines
to produce 𝛽-amino thioesters. Enolate formation is achieved by reductive soft enoliza-
tion. The 𝛼-iodo thioester is a shelf-stable latent enolate.62
de
2,2,2-Trifluoroethanol (TFEA; pKa = 12.40) activates a one-pot reaction of 𝛽-nitro-

enamine (48), benzaldehyde, and piperidine to give a Mannich-like product (49). TFEA
is believed to activate the aldehyde via its acidity and hydrogen-bonding ability, allowing
it to react with piperidine to form an iminium ion, which then reacts with the iminium
zwitterionic tautomer of enamine (48). Control experiments and MS detection of the
first iminium intermediate support the mechanism.63
N-Aryl-3-hydroxyisoindolinones (50; R = OH) react with alkyl aryl ketones under
Lewis acid-catalysed anhydrous conditions to give the corresponding substituted
Pip
O2N CHO
O2N
EtOH
+ +
HN NH 83%
N
H HN NH
(48) (49)
isoindolinones (50; R = CH2 COPh for the case of acetophenone). Evidence for an
N-acyliminium ion intermediate is presented.64
O
O H PG O
HN
N ( )n ∗
N Ar R CN NHBoc
R
N
Cl Cl
R
(50) (51) (52) (53)
Simple cyclic amides with an electron-withdrawing group on nitrogen (51; n = 1–3)

undergo direct catalytic asymmetric Mannich-type reaction with N-Boc aldimines. An
electron-withdrawing group is not required at the 𝛼-position. Mannich adducts can then
be further modified at the amide position, including removal of the 7-aza-indole moiety
if desired. Catalysis is provided by copper(I) and Barton’s base (2-tert-butyl-1,1,3,3-
tetramethylguanidine), with chiral phosphines being employed for stereoselectivity.65
𝛼,𝛼-Dichloro-𝛽-aminonitriles (52) have been prepared via an enantioselective
Mannich-type reaction of dichloroacetonitrile with protected aldimines, RCH=N–PG,
using chiral bis(imidazoline) catalysts ‘pincing’ palladium. Silver acetate and potassium
carbonate are also employed in a process which gives high yields and ees in THF
at 0 ∘ C. At first sight, a strong base might appear to be indicated, but 𝛼,𝛼-dichloro
carbanions (including the current one, − CCl2 CN) are unstable. So a weak base and
palladium activation is the more effective strategy. The products (52) can be converted
to 𝛽-amino-nitriles or -amides without loss of enantiopurity.66
ee
A simple 𝛼,𝛽-unsaturated 𝛾-butyrolactam (53) undergoes a direct catalytic asymmetric

Mannich-type addition reaction with an 𝛼-ethoxycarbonyl N-thiophosphinoyl ketimine,
Ph–C(CO2 Et)=N–P(=S)Ph2 . Using copper(I) catalysis, a chiral diphosphine inducer,
and triethylamine, ee up to 91% is achieved.67
ee
Direct Mannich-type reactions generating both 𝛼- and 𝛽-amino esters from a range
of carbonyl compounds and aldimines have been described. Using a sterically frus-
trated Lewis acid/Brønsted base pair, B(C6 F5 )3 /1,2,2,6,6-pentamethyl-piperidine, high
des have been achieved under mild conditions.68
de
Aldimines of glycinates undergo catalytic enantioselective Mannich-type reaction

with N-sulfonyl imines, using a chiral guanidine catalyst, in good yield and fair ee,
providing a route to 𝛼,𝛽-diamino acids. Previous examples featured ketimines of
glycinates.69
de
Enoldiazoacetamides (e.g. 54) undergo catalyst-controlled divergent reactions with

nitrones: (i) a CuBF4 –bisoxazoline complex favours 3 + 3-cycloaddition, whereas (ii)
CuOTf catalyses nearly exclusive Mannich addition in high yields. 1 H NMR and other
evidence suggests that the first catalyst favours metal carbene generation within a few
minutes, whereas the enoldiazoacetamide (54) is relatively inert in the presence of cop-
per triflate on this timescale.70
ee
O
OTBS O
Ph
NEt2 N
N2
PO(OMe)2
(54) (55)
Isoindolin-1-one-3-phosphonates (e.g. 55) are easily prepared at ambient temperature

in 40 min under solvent- and catalyst-free conditions from three components: 2-formyl
benzoic acid, benzylamine, and trimethyl phosphite (in this case). This version of the
Kabachnik–Fields reaction shows de >94% for the 𝛼-methylbenzylamine case.71
de
A redox-annulation of a cyclic amine (56) and a 𝛽-keto-aldehyde (57) yields a

benzo[a]quinolizine-2-one (58) in refluxing acetic acid/toluene with moderate to good
de. The new intramolecular redox-Mannich process probably involves azomethine
ylides as intermediates. Products such as (58) are known to be in equilibrium with the
corresponding ring-opened isoquinolinium ions, so the diastereoselective ratio of the
products likely represents the equilibrium ratio. In a sample case, the diastereomers
were separated and both subjected to the reaction conditions, resulting in identical de.72
de
O O MeO
MeO H
N
MeO
NH H
MeO
(57)
(56) (58)
O
3-En-1-ynamides (e.g. 59) undergo gold-catalysed imination/Mannich cascades in a

one-pot reaction with benzaldehyde and aniline, giving 1,5-iminoamines (60) with some
diastereoselectivity. Control experiments show that gold-catalysed aminations of the
enynamides (59) yield 𝛼-imino allylgold intermediates. Substrates such as (59) give
(anti-60) products, whereas if the alkene is cyclic, syn-selectivity is obtained.73
de
Ph
Me Ts Ph–CHO Ph Me N
N Ph Ts
Ph–NH2 N N
Ph Me H
Ph Me
(59) (60)
Other ‘Name’ Reactions of Imines

Aza-Henry reaction of a nitroalkane with an isatin-derived N-Boc ketimine is catalysed
by a quinine derivative, giving high ee. DFT has been used to probe the origin
of the selectivity. C–C bond formation is found to be both the rate-determining and
the stereo-controlled steps. Multiple non-covalent interactions, including classical
and non-classical hydrogen bonds and anion· · ·𝜋 interactions, act cooperatively to
give the high reactivity and high ee.74 DFT has been used to probe chiral hydrogen-
ee
bonding catalysts of aza-Henry reactions. The results highlight the role of cooperative
effects arising from non-covalent attractions as a vital factor governing stereoinduc-

de
tion, whereas unfavourable steric interactions were the dominant factor controlling
diastereoselection.75
ee
A self-catalysed aza-Henry reaction of ethyl nitroacetate on chiral trifluoromethyl

aldimines, F3 C–CH=N–R*, works without solvent. The product 𝛽-amino 𝛼-nitro tri-
fluoromethyl esters are easily reduced to 𝛼,𝛽-diamino acid esters. The reactions can also
be catalysed by Lewis acids such as ZrCl4 or AlCl3 .76
de
New recyclable polymer-supported chiral thioureas have been tested in solvent-free
aza-Henry and nitro-Michael additions, giving good ees at low catalyst loading.77
ee
An iminium activation of aromatic aldehydes has been exploited in an organocatalytic

domino aza-Michael–Henry reaction of N-(2-formylphenyl)sulfonamides with trans-𝛽-
nitro olefins, to give 3-nitro-1,2-dihydroquinolines (61) in high yields and up to 88% ee
at ambient temperature.78
ee
In an exploration of carbene catalysis ‘beyond NHCs’, a cyclopropenylidene has been

tested in aza-Morita–Baylis–Hillman (aza-MBH) reactions, using an umpolung strategy.
Bis(dialkylamino)cyclopropenylidenes (‘BAC’s, 62), first isolated in 2006, are easily
synthesized and stable, and are among the least hindered carbenes as the bulky dialky-
laminos are nevertheless far from the carbene centre. They are stronger 𝛿-donors than
NHCs, and comparable 𝜋-donors. In a model aza-MBH test of N-tosylbenzaldimine
and cyclopent-2-enone with DBU as base, BAC (62; R = Pri ) indeed proved superior
to NHCs, CAACs [cyclic(alkyl)(amino)carbenes], and P- or N-centred Lewis bases.79
Sulfonated benzaldimines with an ortho-alkynyl moiety undergo enantioselective aza-
MBH reactions with enones in one pot, using a combined chiral phosphine/gold cataly-
sis, to give dihydroisoquinolines.80
ee
MO6-2X calculations on a model aza-MBH reaction have identified a pathway with

explicit involvement of formic acid in the rate-determining step. Substrate and medium
NO2 R2
X
OH
N R
N N
Ts
R2N NR2 R Cbz R1
(61) (62) (63) (64)
dependence have also been studied and compared with previous work, revealing consid-
erable mechanistic complexity.81
Stereoselective Hydrogenation of Imines, and Other Reductive Processes

Ruthenium–sulfur complexes have been used to catalyse reduction of ketimines,
Ar1 C(Me)=NAr2 , by either hydrogenation or transfer hydrogenation, and via different
types of mechanism: cooperative activation of dihydrogen or hydride and proton.82
Hydrogenation of N-benzylidene-tert-butylamines by tris(2,6-difluorophenyl)boron
via frustrated Lewis pair (FLP) catalysis has been studied for 16 ring-substituted imines.
pKa values for the imines were determined quantum-chemically and correlate directly
with those of the corresponding amines. Structure–reactivity relationships are discussed
in terms of ΔpKa and Hammett’s 𝜎 parameter, or with measured rate constants.83
The reduction potentials of 30 N-(phenylethylene)anilines, X–C6 H4 –C(Me)=N–
C6 H4 –Y, have been determined. As the radical anion product has an electronic distribu-
tion which is like that of the excited state, the authors suggest that Hammett parameters
are insufficient or inadequate for describing the substituent effects, and so they employ
excited-state substituent constants instead.84
Sulfinamide phosphinates have been used as chiral catalysts for enantioselective reduc-
tion of imines.85
ee
The design of new sugar-based ligands for asymmetric transfer hydrogenation from
readily available feedstocks is the subject of a short review.86
ee
Asymmetric transfer hydrogenation of 1-methyl-3,4-dihydroisoquinoline and its 6,7-

dimethoxy derivative shows unusual ee behaviour when catalysed by a cyclopentadienyl
iridium diamine in formic acid/trimethylamine. Initially the product amines are pre-
dominantly (R)-, with >90% ee, but this decreases over time. It is not due to product
racemization, but rather due to a difference in kinetics of the formation of the enan-
tiomers: (R)- follows first-order, while (S)- is zero order. The results are accounted for
by a difference in the rate-determining steps of the routes to the enantiomers.87
ee
N-Substituted diarylmethanimines, Ar1 Ar2 C=N–CH2 –R (R = H, Me, CO2 R), have

been enantioselectively hydrogenated (30 atm/1,4-dioxane/ambient) using iridium com-
plexed with a chiral ferrocene biphosphine. Yields are near-quantitative, with ees from
94% to 99.4%, and turnover numbers of up to 4000. Catalyst loading was typically
0.025 mol%.88
ee
C,N-Diarylketimines, Ar1 –C(Me)=N–Ar2 , undergo asymmetric transfer hydrogena-

tion using ammonia borane (H3 N⋅BH3 ) as hydrogen source, giving the corresponding
amines in up to 95% ee. The catalysis is by a very simple FLP: Pier’s borane
[HB(C6 H5 )2 ] and (R)-tert-butylsulfinamide, with pyridine as an additive. Evidence

from computation, NMR, and control experiments suggests an eight-membered cyclic
transition state.89
ee
Chiral diamine Noyori–Ikariya ruthenium(II) and rhodium(III) half-sandwich com-

plexes catalyse hydrogenation of cyclic imines in high ee, with TFA employed to activate
the substrates. Transfer hydrogenation, using formic acid/triethylamine, is also success-
ful for some of the catalysts. Inert atmospheres are not required.90
ee
Asymmetric hydrogenation of imines contained within seven-membered rings (63;

X = O, CH2 , NMe, S, and SO2 ) is catalysed by iridium(I) complexed with ‘P–OP’
(phosphine–phosphite) ligands on BINOL scaffolds. DFT has helped identify N–H· · ·
Cl, C–H· · ·𝜋, and C–H· · ·H–Ir non-covalent interactions which may be responsible for
the ee.91
2-Pyridyl ketones are converted to chiral diaza ligands via reductive amination with
anilines, using a Hantzsch ester as reductant and a buttressed BINAP–phosphoric acid
auxiliary as catalyst, with yield/ee up to 98/94%.92
ee
Using isopropanol as a hydrogen source and a new moisture- and air-stable ruthenium
catalyst, benzylideneanilines formed in situ are reduced to amines in high yield.93
Quinolines have been directly alkylated by aldehydes (R1 –CHO) via acylquinolinium
ions generated using benzyl chloroformate, avoiding the need for N,O-acetals. In situ
reduction with borohydride gives diastereomeric 1,2-dihydro-quinolines (64) in fair to
good yield, up to 66% syn-de, and up to 99% ee, with typically ca 10–20% of the 1,4-
dihydro-isomer. Selectivity is induced by a commercially available diarylprolinol TMS
de
ether. Products (64) can also be efficiently re-aromatized if desired.94

ee
Without the need for liquids or noble metals, 5 mol% zinc acetate catalyses hydrosily-
lation of N-tert-butylsulfinylimines in up to 98% de, using triethoxysilane as hydrogen
source; the reaction works well for both aromatic and aliphatic ketimines.95
de
Decarboxylative trichloromethylation of N-sulfonyl aldimines yields trichloromethyl

sulfonamides. No catalysis as such was required: the reaction (followed by IR) works in
DMSO at ambient temperature. High diastereoselectivity can be achieved, and solvent
effects have been explored.96
de
A C2 -symmetric diastereomeric secondary amine (65) has been prepared by reduc-

tive self-condensation of unsubstituted acetophenone imine [Ph–C(Me)=NH] using a
Hantzsch ester as reductant, together with a buttressed BINAP–disulfonimide auxiliary
as catalyst, in up to 98% de and 98% ee. The reaction was extended to N–H imines of
substituted acetophenones, and to substrates with naphthalene or pyridine as the aromatic
de
moiety.97
ee
Ph
Ph O
R1
P
Ph N Ph P R2
H Ph N
Ph
(65) (66) (67)
Stereoselective Allyl-, Aryl-, Alkenyl-, and Alkynyl-ations of Imines

Indium(III) triflate catalyses enantioselective allylation of isatin-derived ketimines via a
chiral imidazolylpyridine ligand, using allyltributyltin as allylating agent.98
ee
A copper-hydride catalyst allows homoallylic amines to be prepared from simple

allenes and protected aldimines. Complementary conditions allow formation of either
branched product with high syn-selectivity or linear product with exclusive E-selectivity,
with high de in both cases.99
de
Allylrhodium species derived from 𝛿-trifluoroboryl-𝛽,𝛾-unsaturated esters react with

imines to give products containing two new stereocentres and a Z-alkene. The selectiv-

de
ities observed have been rationalized in terms of rhodium ‘chain walking’ towards the
ester.100
ee
N-Me–BIPAM, a chiral bis(phosphorimidite) containing two BINAPs, induces

enantioselective arylation of aliphatic N-sulfonyl aldimines by arylboronic acids under
rhodium(I) catalysis.101
ee
Copper-catalysed intermolecular enantioselective addition of styrenes to imines has

been achieved under mild conditions, with the styrene featuring as a latent carban-
ion equivalent via a benzylcopper derivative. The reaction depends on chemoselective
hydrocupration of the styrene (over the imine), and mechanistic studies indicate how the
bis(diphenylphospholano)ethane (66) ligand achieves this.102
ee
2-Substituted 3H-indol-3-ones (67) undergo enantioselective aza-Friedel–Crafts reac-

tion with pyrroles or indoles with an imidazoline–BINAP–phosphoric acid catalyst.103
Substituted cyclic tosylhydrazones (e.g. 68) undergo regio- and stereo-selective reduc-
tive coupling with a boronic acid. This stereoselective C(sp3 )–C(sp2 ) bond-forming
reaction works for 2-substituted cyclopentanone-derived hydrazones as well, but not
for acyclic substrates. DFT calculations indicate an asynchronous concerted TS lead-
ing to the intermediate allyl boronic acid, with an equatorial trajectory determining the
stereoselectivity en route to alkene (69).104
de
O
R2 Ar
NNHTs Ar
R3
R2
(72) N O
N
∗
R1 cinchona PTC
B(OH)2
R1 R2 R1 R3
R1 KOH (aq.) R2
(68) (69) (71) (70)
𝛿-Keto-imines (70), related to 𝛾-aminoketones, have been generated chemo-, regio-,

diastereo-, and enantio-selectively by an umpolung reaction of simple ketimines (71)
de
and enones (72), using a phase-transfer catalysis based on a cinchona alkaloid.105

ee
Chiral propargylamines have been prepared by catalytic asymmetric Friedel–Crafts-

type arylations of C-alkynyl imines. The approach is complementary to previously devel-
oped alkylations and alkynylations.106
ee
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Never before had he pitched in the presence of a crowd of such
crude, seemingly ferocious, human beings; but many a time, as he
well knew, he had faced batters as skillful and dangerous as these
raw, would-be professionals and broken-down cast-offs from minor
leagues.
At no time had he feared the hitting ability of his opponents, but,
as sometimes happens to the headiest and most seasoned veteran,
the moment he toed the slab some incomprehensible thing had
taken possession of him, and made him a mockery for the crowd and
a sickening shame to himself.
Now, however, he knew the unmanning spirit had been exorcised;
he was himself again, clean and fit.
CHAPTER VIII
STEADYING DOWN
T om Locke did not turn his eyes toward the bench; he did not
dare, lest a glance should be interpreted as a supplication, and
bring about his removal from the field. He saw Oulds, ball in hand,
standing squarely on the plate, while “Wop” Grady, the next batter,
eager to keep things going and gain as much advantage for Bancroft
as possible before another pitcher was sent in, was seeking to push
him back into his position.
His manner entirely changed, although his face continued ashen,
Locke beckoned to the catcher, and ran forward. Oulds, scowling,
sour, sullen, met him five feet in front of the pan.
“Give me that ball,” said Locke, taking it from the catcher’s hand.
“Call the curves: a drop or a high inshoot for a strike-out, whichever
you happen to know this man is weakest on. I’m going to get him.”
“Yes, you are!” sneered Oulds. “Why, you can’t—”
“Get ready to catch me,” Locke cut him short. “I tell you I’m going
to get this man.”
Then, seemingly deaf to the continued howling of the crowd, he
turned and walked back, apparently disregarding the taunting base
runners, who were dancing off the sacks to lure a throw.
Larry Stark, doubtless wondering that Hutchinson had not signaled
for a change, stood listless, twelve feet off second; but, without
betraying the fact, Locke observed that Jim Sockamore, the Indian
center fielder, apparently hoping to work an old trick in the midst of
the excitement, was walking swiftly, but unobtrusively, in toward the
sack. Indeed, Sockamore was not twenty feet from the bag when the
pitcher faced Grady at the plate.
Only for an instant were Locke’s eyes turned toward the batsman;
like a flash, he whirled again to face second, and the ball shot from
his fingers as he turned.
He had not received a signal to throw, but he did so on the chance
that the foxy Indian player would sneak all the way to the hassock, if
for no other purpose than to show up what might have been pulled
off with a live pitcher on the slab.
Sockamore was within five feet of the cushion when Locke turned,
and, seeing the ball was coming, he leaped forward. Harney, not a
little surprised, lunged back. Like a bullet the scarcely soiled ball
sped straight into the eager hands of the young redskin, who met
Harney and jabbed it on to him viciously as the Bancroft captain
weakly sought to slip under.
The howling of the angry and dissatisfied crowd was instantly cut
short. The sudden silence was ruptured by a single hoarse word shot
from the lips of the umpire, who had been so surprised that for a
moment he had faltered in giving the decision:
“Out!”
The spectators gasped; Harney choked and rumbled weakly.
Sockamore grinned into the face of the tricked and chagrined man.
At the bench, Henry Cope brought his hand down with a resounding
slap upon his thigh, crying jubilantly:
“There! He got him!”
After a few moments of dazed silence, some scattered persons
ventured to applaud and cheer faintly, while, apparently struck by the
seeming incongruity of the unexpected performance, many others
laughed.
“Oh, what an accident!” groaned one of the coachers, as Harney,
his face red with mortification, rose to his feet and gave Locke a
stare.
“How’d you ever happen to think of it?” sneered the Bancroft
captain.
Chuckling, Sockamore threw the ball to the pitcher, and capered
back into center field. Harney, his mouth twisted and his cheeks
burning, made slowly for the Bancroft bench.
“Accidents will happen,” came from a coacher. “Never mind that.
Take a constitutional, Wop; he’ll accommodate ye.”
Grady idled at the pan, laughing silently over the discomfiture of
his captain. He was still idling when Locke, seeing Oulds ready, shot
over a scorcher that clipped the inside corner.
“Strike!” declared the umpire.
“What’s that? What’s that?” cried the coacher. “It can’t be poss-i-
bill? Another accident!”
Surprise was general, but still, like the coacher, the spectators on
the bleachers and in the stand fancied it related in a way to
something “accidental,” and not one in a hundred thought it probable
that the left-hander could put over another without wasting several.
Oulds, wondering, called for an out-drop, but Locke, knowing the
batter had not yet been egged into a condition that would make him
easy to “pull,” shook his head. The signal was changed to one
requesting a straight drop, and the pitcher swung into a snappy,
quick delivery.
The ball seemed to be too high, and not looking for the despised
twirler to “put much on it,” Grady permitted himself to be caught
again. Down past his shoulders shot the sphere, to the instant
croaking of “Strike tuh!” from the umpire.
“Hey, hey! What’s comin’ off here?” bellowed an uncoated,
unshaven, collarless man back of first base. “Lightnin’s hit agin in the
same place.”
CHAPTER IX
SOME PITCHING!
T here was a change in the aspect of the crowd and its behavior,
for this was more like something worth while, and a few were
beginning to think it possible they might have underestimated the
ability of the southpaw slabman. Yet, lost confidence had not been
wholly restored, and they waited to see what the final result would
be, the Kingsbridgers silent, the Bancroft crowd still laughing and
scoffing.
“Never mind, Wop,” called the coacher at third. “He can’t do it
agin. If he does, give it a ride. Come on, Trollop; git off that mattress
—tear yourself free. On your toes! Ready to scorch if Wop biffs it. Git
away, away, away off! More than that! I’ll watch the ball. Come on!
Come on!”
Locke drove Trollop back to the sack once, following which he
quickly pitched the third ball to Grady. He had a way of throwing
every one in almost precisely the same manner, which prevented a
batter from judging what was coming by his style of delivery. It
looked like another high one that might turn into a drop, but it proved
to be a fancy inshoot, and Grady, doing his prettiest to connect,
made a clean miss.
“Y’u’re out!” barked the umpire.
Then the crowd did cheer, for, in amazing contrast to the manner
in which he had opened up, Tom Locke had whiffed Grady without
wasting one.
Henry Cope poked the silent Hutchinson in the ribs. “What’d I tell
ye? What’d I tell ye?” he spluttered delightedly. “Now I guess you’ll
see I ain’t such a bonehead in pickin’ pitchers. I played this game
myself once.”
“Wait,” said the manager without a flutter, or the slightest variation
of intonation. “Strikin’ out one man that’s looking to walk don’t make
a pitcher. He’s got to show me more’n that.”
“He’ll show ye, all right,” asserted Cope. “I knew what he c’d do.”
Gus Mace followed Grady at the pan. The right fielder of the
Bullies, he was regarded as their heaviest hitter, and his batting the
year before had caused the Kingsbridgers to groan with grief. He
was boiling over with confidence as he faced Locke, but, getting a
signal from Riley, he let the first one pass, in order that Trollop,
grown weary of camping on first, might try to steal.
It was a strike, and Oulds winged it to second in the effort to nail
the runner, who had made a flying start and was burning up the
ground. Trollop slid, spikes first, and Stark, who seemed to have him
nipped, dropped the sphere in the attempt to avoid those spikes and
tag the man at the same time. Trollop was safe.
“Now’s the time, Mace!” cried the coacher back of third. “Hit it out.
Give it a long sail, and let Andy walk home.” He had dropped his
chatter about waiting for a pass.
Mace gripped his trusty war club and waited, crouching a little. It
was plain that the Kinks’ new pitcher had recovered his control, and
the batter meant to hit anything that came across. He struck left-
handed, and the next one pitched looked good to him. It dragged him
almost across the pan, and he did not even foul it lightly.
A sharp yell went up from the once-more vibrant and excited
crowd, but this time it was a yell of satisfaction. Choking, agitated
men began to predict that Lefty would fan Mace, also.
“If he does,” said one, “I’m goin’ to throw a fit right here! I’ll own up
honest that I’m the biggest fool that ever barked like a sore-eared
pup at a good man.”
The Bancrofters were still trying hard to rattle Locke, but now,
absolutely cool, self-possessed, and confident, he gave no more
heed to their racket than he might to the buzzing of a single fly.
There was something in his clean-cut face, his steady eyes, firm
mouth, and deliberate manner which proclaimed him absolute
master of himself, and predicted that he also would show himself
master of the situation.
Oulds, his confidence completely restored, grinned through the
meshes of the wire mask. “I reckon you was jest monkeyin’ with ’em
boy,” he said. “They’ll all look alike to ye from now on. This one’s jest
as easy as any.”
And so it proved, for Big Mace slashed again, and found nothing
but empty air; whereupon the Kingsbridge crowd rose in a body and
roared a splendid salvo for the man they had been reviling and
threatening a short time before.
As that burst of applause died away, a Neapolitan laborer,
standing on the bleachers, his shirt open at the throat, the oily, blue-
black hair of his bared head shining in the sun, his kindled eyes
almost popping, and his teeth flashing like scimitars, shook his grimy
fists in the air, and screamed:
“What’s-a da mat’ with-a da Lefty?”
The answer was a great shout of laughter, and another hearty
round of applause, which told how suddenly and completely the
humor of that recently raging and reviling assemblage had altered.
He whom a few minutes before they were deriding and threatening,
had, by his amazing performance, become the admired idol of the
moment, the Horatius at the bridge, the Moses to find the promised
land.
They were more than willing to accept him as king of warriors and
savior of wilderness wanderers, but to retain his scepter he must still
further demonstrate his prowess in battle or his ability to smite a dry-
shod pathway across a mythical Red Sea.
CHAPTER X
A PITCHERS’ BATTLE
A s Locke walked calmly toward the bench he found Captain Stark

at his side, laughing. “You pulled outer that hole in great shape,
old man,” said Larry; “but you sure had us all leery to start with. I
reckoned you was plumb up in the air.”
“I was,” admitted the pitcher unhesitatingly; “but I managed to get
my feet under me after a while.”
His face was no longer pale; the color had returned to his cheeks,
and a flickering smile played at the corners of his fine mouth.
Henry Cope, beaming, made room for the players on the bench. “I
knowed it,” he said. “I tole ’em so.”
Having unemotionally watched the new pitcher approach,
Manager Hutchinson spoke to Stark. “See if you can’t start
something right away,” he directed. “Mebbe we’ll get ’em going if we
score the first time up.”
Larry nodded, and whispered hastily to the leading batter, Labelle,
a slim, shifty French Canadian, a heady single hitter, and an
unusually fast man on the sacks. Labelle grinned, and found his bat.
Possibly the Bancroft manager was more disgusted than
disappointed, as the sarcastic comments which he flung at his
offending players seemed to indicate; but as yet he had not been
aroused to apprehension concerning the ultimate outcome of the
game, and he felt that, were the Kinks’ left-hander really formidable,
it had well happened that his men had been forwarned thus early in
the contest.
Having relieved his feelings by a flaying fling at Mace, as the final
victim of Locke’s skill secured his fielding mitt from the bench, Riley
cast aside the remnants of his cigar, lighted a fresh weed, and
prepared to watch Jock Hoover make monkeys of the locals.
Janet Harting was overjoyed. “Oh, wasn’t that splendid!” she cried,
impulsively squeezing her companion’s arm with one gloved hand. “It
was such a surprise! I never expected it.”
“No more did any one, I fancy,” said King, laughing. “It’s the
unexpected that so frequently happens which makes baseball the
fascinating game it is. Apparently that fellow can pitch some, after
all. I wonder where he came from.”
“Mr. Cope won’t tell, and nobody around here seems to know.”
“Somehow I have a feeling that I’ve seen him before, but I can’t
place him.”
“Perhaps he’s some great college pitcher,” said the girl.
“I don’t know about that, but if he is I reckon he’s here under a
fake name; for you know it makes college twirlers professionals to
play for money. A man is barred if he’s ever caught at it. Just the
same, some of them, needing the dough, take the risk. Up here in
this league a man would stand a fair chance of getting by without
being exposed.”
“It’s—it’s supposed to be dishonest, isn’t it?”
“Yes; but necessity has driven more than one good man to shut
his eyes to that phase of the matter. If this Locke was known at all as
a professional, some of the players of this league should recognize
him.”
“I don’t like to think that he’s a college man who would do such a
thing,” said Janet earnestly.
“Oh-ho!” cried Bent. “So you’re taking considerable interest in the
chap you thought couldn’t pitch at all.”
“Well,” she faltered, “he—he looks clean and honest. One can see
he isn’t like the others—the most of them, anyway. Kingsbridge is
going to bat now. I hope they can do something.”
Hoover had shaken the kinks out of his arm by two or three throws
to first, and, glancing round to make sure his backers were in
position and ready, he stepped on to the slab and glowered at
Labelle. Squatting, Bangs signaled, and the fire-eating twirler swung
into his first delivery.
Although a “waiter,” with an excellent eye, Labelle seldom
permitted himself to pass up the first one if it came over the rubber,
and he sought to land on Hoover’s corner-cutting slant. The resulting
foul counted against the batter as a strike.
“That’s a nibble; take a bite,” shouted a coacher.
Labelle stamped his spikes into the ground, and squared himself
again, unruffled. Hoover leered at him vindictively. The crowd rooted.
CHAPTER XI
ON THE RAW EDGE
T wo balls followed swiftly, the batter ignoring them both, although

with every nerve taut.
“Got to put ’em over, Jocko,” called the coacher. “You can’t pull
that little Canuck.”
Hoover handed up a “spitter,” and Labelle missed cleanly.
“He never could touch you,” chuckled the first baseman.
“You’ve got his measure,” declared the shortstop.
“Give him another in the same place,” urged the guardian of third.
“Oh, let him hit,” begged the center fielder. “He won’t get it out of
the diamond.”
Again, and once again, the Canadian fouled; and then Hoover
caught him with a deceptive slant for another clean miss, and
Labelle retired, disappointed.
Stark came next, and, like the leading sticker, his best efforts
resulted only in weak fouls, the Bully on the slab finally sending him
back to the bench by the whiff route, to the loud acclaim of the
admiring Bancrofters on the bleachers.
“They’ll never locate you to-day, Jock,” shouted one of these.
“Show up their southpaw wizard. Make a record.”
Reddy Crandall proved to be quite as easy as his predecessors,
and Hoover finished his first turn with the third straight strike-out, not
even seeming to hear the wild applause of his admirers as he
sauntered, sour and unsmiling, to the bench.
More than one of those admirers, even while fulsome with praise,
had sometimes felt a strong desire to kick the ungrateful, egotistical,
pugnacious star slabman of the champions, who, among his
browbeating teammates, even, was not much courted for his society
off the field.
Riley, the only person who never praised or flattered him, had
discovered some secret process of holding him in check and making
him of inestimable value to the team.
“Now, you fellers,” growled the Bancroft manager, speaking with
the cigar between his teeth, “I want ye t’ go after this left-handed
dub, and chaw him up. Put the willer to him, and break his heart. You
had him almost out when you slipped a cog t’other time. Git to first,
McGovern, and th’ boys will push ye round.”
“I’ll make the sack somehow,” promised McGovern, as he started
out with his big bat, conquest in his heart.
Exactly thirty-two seconds later Pat McGovern came back to the
bench, fanned, having found his left-handed position at the plate
most disadvantageous in batting against the Kinks’ southpaw. Riley
was growling throatily as Otto Bernsteine went forth to pit his wits
and skill against the brains and cleverness of Tom Locke.
To tell the truth, Bernsteine, although usually phlegmatic and
unemotional, was worried; for he, also, hit left-handed, and he had
begun to believe that the Kingsbridge twirler was a terror to batters
who stood at the plate in that manner. His worriment was justified;
Locke got him, also.
The uproar of the crowd drowned the remarks of one Michael
Riley, manager of the Bancrofts; and this may have spared the
nerves of any sensitive person in his immediate vicinity. “Hey,
Lisotte,” he snarled at the shortstop, who was the next in line, “bunt
the ball. D’ye hear? Bunt, an’ try to beat it out. You bat wrong, too,
and ye can’t hit him fair. He’s got the Injun sign on you off-side
sluggers.”
Lisotte did his best, but the first ball he bunted rolled foul, and the
next he tried for, being close and high, was missed completely.
Fearing to try another bunt, he finally swung after one that came
slanting over, and missed that also.
The best stickers of the Bullies had faced Locke in two innings,
and not one had obtained as much as a scratch single off him;
realizing which, the local crowd had spasms of many sorts. With faith
completely restored, the Kingsbridgers were telling one another
exultantly that, at last, the man had been found to hold the hated
enemy in check. Visions of the Northern League pennant waving
over their grand stand at the finish of the season already danced
before their eyes.
The Bancrofters, although saying that the game was young, and
pretending their confidence was as great as ever, were really
suffering the qualms of apprehension, all the more intense and
disturbing because of the early elation they had felt.
When Kingsbridge’s Italian right fielder, Tony Anastace, opened
the second for the locals with a clean safety, this rejoicing on one
side and apprehension on the other was redoubled.
But Jack Hinkey popped to the infield, Anastace was slaughtered
trying to purloin second, and Fred Lace lifted a high foul back of third
for Wop Grady to smother, squaring things up with not a count for
either side.
Although Locke, feeling that he had the confidence of his
teammates at last, seemed to take it easier, a measly scratch single
was all Bancroft could find him for in the third; and, with Hoover
hitting a two-minute clip in the last of the same inning, even the least
astute spectator understood that it was practically certain to be a
pitchers’ battle right through to the finish.
With the passing of the innings, and the failure of his teammates to
score, Hoover steadily became more savage in the box. At times,
under cover of the shouting of the crowd, he insulted the batters with
venomous, blood-tingling words.
Contrary to his usual practice, he sought the privilege of going on
to the coaching line, where his sneers and slurs were of a nature that
aroused protests from the crowd, and finally forced Riley to keep him
on the bench when he was idle.
Locke opened the sixth by fanning Trollop, Grady, and Mace, one
after another; and then, in the final half, he came first to bat for
Kingsbridge.
“Get back off the pan, you peanut-headed sample of nature’s
carelessness,” rasped Hoover, ready to pitch. “Get back, or I’ll take a
rib outer yer!”
“I’m in my box,” returned Locke calmly. “Pitch the ball, sorehead.”
With a murderous expression, Hoover scorched one straight at his
rival, and Tom barely escaped being hit by a most amazing,
lightninglike dodge. This brought the Kingsbridge crowd up howling
wrathfully, and Locke, recovering his position at the pan, cried loudly
enough for Hoover to hear:
“Try it again, old boy—try it again, and they’ll be coming after you
with war clubs and scalping knives.”
Captain Harney ran out and grabbed Hoover. “Keep your head,
Jock—keep your head,” he begged. “He’s won the crowd. He’s got
’em with him. You’ll start a fight that’ll mean busted heads if you hit
him on purpose.”
Already two constables, wearing their badges displayed, were
having their hands full to keep back a few hot-headed ones, who
seemed eager to charge upon the diamond to reach Hoover.
CHAPTER XII
THE “SQUEEZE PLAY”
In a town like Kingsbridge, such a movement meant a general

stampede, followed by a riot, in which more than one participant
would “get his.”
Harney continued to talk to Hoover until the raging pitcher, the
freckles on his face seeming to stand out like innumerable islands in
a grayish sea, promised to behave. The umpire seemed practically
helpless.
Locke had waited quietly. He gripped his bat, and squared away
as he saw Hoover making ready. The ball came over the outside
corner with a shoot, and Tom met it. It was a beautiful, clean single
into right field.
The crowd was still roaring when Labelle rushed forth to the pan,
signaling that he would attempt a sacrifice. Locke was on his toes,
and ready, and he started as Hoover began his short delivery. True
to his signaled promise, the Canadian dropped a bunt in front of the
pan, thus easily giving the runner ahead of him second, although he
himself was cut down in his last jump for first.
With one out, a runner on second, and Captain Larry Stark ready
to wield the willow, the local crowd whooped it up like crazy Indians
at a ghost dance, believing Kingsbridge had its chance to score.
It was plain that the new pitcher, besides being fast on his feet and
ready to take chances, had the faculty of leaping away almost at top
speed with his first stride or two, and a long, clean single might
enable him to score from second.
Hoover knew this, and was inwardly disturbed. Although he had
already twice cut Stark down at the pan, previous experiences
warned him that, as a batter to advance runners, the cool, heady,
sure-eyed Kingsbridge captain was far more dangerous than the
heavier-hitting Crandall, who followed him. Therefore, being
supported by a sign from the bench, Jock decided to pass Larry, and
take his chances with Crandall and Anastace.
First driving Locke back twice to second, but being unable to keep
him hugging the cushion, Hoover handed up a wide one with such
elaborate method that he betrayed his purpose immediately.
Promptly with the next pitch, something happened: Locke was
leaping away toward third before the ball left Jock’s fingers. Grady
covered the sack, and Bangs scorched the air with his quick line
throw, but the runner slipped under, and was safe by a narrow
margin. Bill Harney disputed the decision, while the crowd howled;
but the umpire waved him back to first.
Eyes bulging, throats dry, nerves twitching, the Kingsbridge
spectators rooted for a run. Some were purple-faced and perspiring;
others were pale and cold; all were wrought to the highest pitch of
expectation and excitement.
The face of the wrothy Hoover was twisted into a snarl, and, as the
ball came back to him, he betrayed momentary indecision.
Immediately Locke caught a signal from Stark, given by the
Kingsbridge captain with his back toward third, his attention
seemingly focused on the man on the slab, and the runner knew
Larry would seek to hit the next pitched ball if he could possibly
reach it without stepping out of the box. Crouching like a runner
ready for the crack of the starter’s pistol, Locke crept off third.
The ball was wide of the rubber, but, reaching far across, Stark
found it with the end of his long bat, and tapped it into the diamond,
immediately getting away on the jump for first.
Locke had not failed to obey the signal for the “squeeze,” and he
was coming like the wind when the bat and ball met. Hoover forked
fruitlessly at the ball as it caracoled past, but it was McGovern who
scooped it, and lined it home in hope of nipping the runner.
A blighted hope it was, for the flying man slid safely, and Bangs,
recognizing the uselessness of trying to tag him, winged the sphere
to first, where it arrived a moment too late to get Stark.
Far better than words, imagination may picture the uproar of that
hysterical moment.
Gradually the cheering ceased, and the hoarse and happy
Kingsbridgers became semirational. To Stark, in a way, as much
credit was due for that finely worked squeeze as to Locke; but it
seemed that the name of the latter was on every lip. He had made
the play possible by his hit and steal, and the delighted crowd
howled blessings at him long after he was seated on the bench.
Locke’s manager looked him over unemotionally, and then sent
Crandall out to the pan, with instructions. Hutchinson did not believe
in spoiling a youngster with praise. Furthermore, the game was far
from over, and experience had taught him that the time to count
chickens was after the hatching.
One man, at least, was wholly happy; Henry Cope was confident
that, after this, his fellow members of the Kingsbridge Baseball
Association, who had given him carte blanche to secure a star
pitcher, at any price, could not make much protest when they learned
that he had contracted to pay Tom Locke one hundred dollars a
week and board, a sum far greater than many a minor-league pitcher
of promise received.
Janet Harting was delighted beyond words; so delighted, indeed,
that her ebullient expressions of joy and unreserved admiration for
Locke brought a slight frown to the dark face of Benton King.
There were those, however, who felt no touch of rejoicing.
The Bancroft crowd was silent. Mike Riley sat on the bench, and
chewed at his dead cigar, turning only to snarl at Fancy Dyke when
the latter called to him anxiously from behind the rail. He had already
sneered at his players because of their inability to hit Locke, but
there was something of a still more caustic nature awaiting them
when they should again assemble at the bench.
CHAPTER XIII
THE LAST STRIKE-OUT
B ut no man on that field felt the sting of the moment as deeply as

Jock Hoover, in whose heart hatred for Tom Locke burned like
living fire. The wonder and terror of the league, he feared that a
blazing sun had risen to eclipse him. The effect upon him was fully
apparent when he carelessly let Stark steal second behind his back,
which brought upon him the amused scoffing of the Kingsbridgers.
Nor did it serve to lessen the bitterness of his soul when, although he
still burned the ball over with the sharp slants which an expert “spit
artist” commands, Crandall leaned against it for a grasser to right,
and Stark, spurred by the shrieking coacher, crossed third, and
reached the home plate, adding another tally.
After that, Anastace popped, and Hinkey agitated the air; but the
damage was done.
Riley’s scathing, acrid arraignment of his batters did no good.
Although an error let Mace get to first in the seventh, Locke disposed
of the next three stickers with ease, and apparently without any great
exertion.
Hoover returned to the slab in form, and closed the inning with
three straight to his credit.
For Bancroft, hope revived when Bangs started the eighth by
obtaining a pass, the first to be secured from Locke since the initial
inning. Hoover strode out, thirsting for a hit. Had the stab of his eyes
been deadly, Tom Locke must have dropped, mortally pierced, in his
tracks.
With the head of the list coming up, Riley had called for a sacrifice,
and, much as he hated to do it, Hoover sought to obey. He did not
even foul the first ball he tried to bunt; but Oulds, in his haste to get
Bangs going down, made a bad throw, and the runner reached
second base.
“Ah!” thought Jock exultantly. “Now I can hit it out!”
But he could not hit it out, although he did his best. Locke sent him
to the bench, fanned and furious.
Harney, however, batted a lingerer into the diamond, and little
Labelle eagerly overran it, which put two on the sacks.
It was still a game, and the Bancroft crowd was beginning to froth,
while the Kingsbridgers felt their nerves shaking again. With two on,
only one out, and Trollop and Grady to hit, all sorts of things might
happen.
What really happened was two strike-outs, which went to the credit
of the Kingsbridge southpaw, and made Janet Harting declare she
“just wanted to hug him.”
Locke was one of Hoover’s victims in the eighth, which, however,
did not seem to disturb his equanimity in the least, and gave the
Bancrofter but poor and unsatisfactory solace. There was no run-
getting, and the ninth opened with the Kingsbridgers rooting for
Locke to choke it off in a hurry.
The “Bullies” always fought to the finish, and they were in the
game to take advantage of anything favorable that might happen.
Once more Labelle, who should have easily handled Mace’s
grounder for an assist, became too eager, and failed to get the ball
up cleanly, following with a poor throw that presented the runner with
“a life.”
Standing, every man Jack of them, the Bancrofters on the
bleachers whooped things up desperately. They were disheartened a
bit when McGovern hoisted an infield fly, and went to the bench; but
they awoke with redoubled energy as Bernsteine bingled a bone-
breaker against Fred Lace’s shins, and the third baseman chased it
long enough to make fruitless any attempt to get the man.
“Come, Lefty,” shouted a Kingsbridger; “you’ll have ter do it alone.
You ain’t gittin’ no s’port.”
And now, as if he, too, felt the strain of it, and the tension was too
much, Tom Locke handed up four balls, and filled the sacks.
“It’s the same old story!” shouted Harney from the coaching line.
“They’ve gone to pieces again! We’ve got ’em! We’ve got ’em! We
win it right here! Old southpaw is making an altitude record! He’s
gone! He’s up out of sight now! He’ll never come down! Kill it, Bingo,
if he puts one across!”
Kingsbridge was apprehensively silent, taut, and choked with
dread; Bancroft howled and screamed like a lot of caged Camorrists.
Bangs gripped his club, longing for a two-bagger, or even a long,
clean single. Locke took his time, absolutely declining to betray signs
of agitation similar to those which had marked his advent upon that
field.
“You’ve got to do it, Lefty!” came entreatingly from the man who
had shouted before. “If you fail us now, there’ll be a fun’rul after the
game.”
Locke whipped over a high one.
“Strike!” blared the umpire.
Before Bangs had finished kicking at the decision, the pitcher bent
over another.
“Strike tuh!”
“Get against it, Bingo—get against it!” yelled Harney. “Spoil the
good ones, anyhow.”
Two balls followed. Then came a marvelous drop that Bangs
missed by many inches, and Kingsbridge roared, drowning the
Bancroft groan.
Jock Hoover had been swinging two bats. He dropped one of
them, and walked into the box, stooping a moment to rub his palms
on the dry dirt. Never in his life had he desired half as much to get a
hit, and never had he believed more firmly that he would get one.
“You’re the boy, Jock!” shrieked a rooter. “Bring ’em home! Win
your own game, old fightin’ cock!”

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Organic Reaction Mechanisms 2016

Typeset in 10/12pt TimesLTStd by SPi Global, Chennai, India.

K. K. BANERJI Department of Chemistry, J. N. V. University,

C. T. BEDFORD Department of Chemistry, University College

M. R. CRAMPTON Department of Chemistry, University of Durham,

N. DENNIS 3 Camphor Laurel Court, Stretton, Queensland,

D. A. KLUMPP Department of Chemistry, Northern Illinois

P. KOČOVSKÝ Department of Organic Chemistry, Charles

K. C. WESTAWAY Department of Chemistry and Biochemistry,

1. Reactions of Aldehydes and Ketones and Their Derivatives

Reactions of Aldehydes and Ketones and Their Derivatives

Formation and Reactions of Acetals and Related Species . . . . . . . . . . . . . . 2

Formation and Reactions of Acetals and Related Species

Organocatalytic enantioselective routes to two classes of cyclic acetals have been

Treatment of 𝛼-diazo-𝛽-ketoesters (3) with cyclic ketones, lactones, or carbonates

Enantiomeric acetals (10) show a surprising difference under reductive cleavage by

BINOL-based trifluoromethyl aryl ketones (15; R = H or CH2 OMe) act as fluores-

Alkynylhemiaminals (17) can be prepared from propargyl aldehydes, or oxidatively

Enantioselective aminomethylation of 𝛼,𝛽-unsaturated aldehydes, R–CH=CHCHO,

For a reactivity scale for N,O-acetals, see the ‘𝛼-Aminations’ section.

3,4,5-Trimethoxybenzaldehyde undergoes reversible dithioacetal formation (21) with

The origin of 𝛼-(1,2-cis) selectivity in galactosyl and galactosaminyl donors with a

Glycosyl methanesulfonates undergo regio- and stereo-selective couplings with par-

A popular urea organocatalyst, N,N’-bis[3,5-bis(trifluoromethyl)phenyl]urea, has been

1-O-Acetylfuranoses and pyranose 1,2-orthoesters act as excellent glycosyl donors

Reactive boron species are useful in sensing applications of d-fructose. A kinetic

Reactions of Ketenes and Related Cumulenes

𝛼-Addition of aldehydes (e.g. Pr–CHO) across allenamides, H2 C=C=CH–N(R)Ts,

Formation and Reactions of Nitrogen Derivatives

The kinetics of condensation of 4-methoxybenzaldehyde with 2-aminobenzamide

Trifluoromethyl ketimines, R–C(CF3 )=N–CH2 –Ar, have been enantioselectively iso-

Novel chiral pyridoxamines catalyse enantioselective transamination. The biometric

Copper(I) coupling of a ketone, R1 –CO–CH2 –CH2 –(CH2 )n –Cl (n = 1, 2), a primary

A DFT study has examined Jorgensen–Hayashi-type amines as catalysts of iminium-

Phosphate-mediated Pictet–Spengler cyclization has been studied by DFT and

Mannich, Mannich-type, and Nitro-Mannich Reactions

The first organocatalysed direct Mannich reaction of unactivated 𝛼-styrylacetates

alkaloid–urea catalyst employed gives yields/de/ee up to 84/92/97%.53

𝛼-Fluoroketones undergo Mannich reaction with N-tert-butylsulfinylimines in up to

A diastereoselective Mannich reaction of an aromatic aldimine and a phenyl oxazoli-

A zinc–proline–phenol catalyst gives high de and ee in Mannich reactions of

quaternary stereocentre in the 𝛼-position.56

A diastereo- and enantio-selective Mannich addition/cyclization reaction of 𝛼-

hydrolysed to give fully substituted 𝛼,𝛽-diamino acids.57

𝛼,𝛽-Tetrasubstituted imidazolines (45) are prepared from 𝛼-substituted 𝛼-isocyano-

yields/de/ee are in the 90s.58

proline and an achiral aminal/urea co-catalyst.59

The enantioselective direct Mannich addition of ethyl acetoacetate to arylideneureas,

benzaldimines to give protected 𝛽-fluoroamines (e.g. 46) with ee/de up to 99/95%.61

2,2,2-Trifluoroethanol (TFEA; pKa = 12.40) activates a one-pot reaction of 𝛽-nitro-

(50) (51) (52) (53)

Simple cyclic amides with an electron-withdrawing group on nitrogen (51; n = 1–3)

A simple 𝛼,𝛽-unsaturated 𝛾-butyrolactam (53) undergoes a direct catalytic asymmetric

Aldimines of glycinates undergo catalytic enantioselective Mannich-type reaction

Enoldiazoacetamides (e.g. 54) undergo catalyst-controlled divergent reactions with

Isoindolin-1-one-3-phosphonates (e.g. 55) are easily prepared at ambient temperature

A redox-annulation of a cyclic amine (56) and a 𝛽-keto-aldehyde (57) yields a

3-En-1-ynamides (e.g. 59) undergo gold-catalysed imination/Mannich cascades in a

Other ‘Name’ Reactions of Imines

A self-catalysed aza-Henry reaction of ethyl nitroacetate on chiral trifluoromethyl

An iminium activation of aromatic aldehydes has been exploited in an organocatalytic

In an exploration of carbene catalysis ‘beyond NHCs’, a cyclopropenylidene has been

MO6-2X calculations on a model aza-MBH reaction have identified a pathway with