Week

1 Mechanisms

CHEM S-20ab

Alex Engler

101: Alkene + H-X

H Br

Br

Br

102: Alkene + H3O+ 103: Alkene + ROH, H+ 104: Alkene + X2 105 & 106: Alkene + X2 + *-OH (* = H or R)
Br
Br Br Br
H OHMe

OH2
O H OH

OH2

OH2

OHMe OHMe
O H OMe

Br

Br

Br

Br

Br

Br

Br

OH2

OH2

OH

OH2

107: Alkene + H2, Pd/C

H2C H H CH2 H3C CH3

H Pd C Pd C

H Pd C

108 & 109: (Alk)Oxymercuration/reduction of Alkenes

Hg AcO OAc

OH2
HgOAc Hg OAc OH2

+ NaBH4

OH2

OH

1/28

Week 1 Mechanisms

CHEM S-20ab

Alex Engler

110: Hydroboration/Oxidation of Alkenes

B H H H H BH2

H2O2 NaOH
OH

111: Ozonolysis w/ reductive workup 112: Ozonolysis w/ oxidative workup 113: Alkene + HBr, ROOR RO
OR

H O

O3

Me2S

OH O

O3

H2O2

Br

Br Br Br

RO

Br

+ Br

2/28

Week 2 Mechanisms
H H H H H H H H H H CH3

CHEM S-20ab

Alex Engler

200: Ring Flip for Chair Conformations

H H H H H H H H H H CH3

201: SN2 Substitution

Nuc:
Rc Rb Rb Ra LG

nNuc -> *LG

Nuc

Ra

Excellent Nuc: CN-, SH-, IGood Nuc: OH-, Br-, N3-, NH3 Poor Nuc: Cl-, CH3O2-, F-, H2O Excellent LG: HI, HBr, HCl, HOSO2R, H3O+ Poor LG: HF, H2S, HCN, H2O, HOR

Rc

STERICS: Excellent if Me,

1o;

Good if

2o,

Poor if

3o

202: E2 Elimination
B:
R1 R2 LG R2 R4

R4 R3

R1

R3

Strong Bases: -OH (NaOH, KOH) -OR (KOtBu, NaOCH , NaOEt) 3 -H (NaH) -C (R-MgBr)

R1

R2

LG

R4 R3

nB -> *C-H C-H -> *C-LG

Br

anti-periplanar has best overlap

Br

KOEt EtOH 71% Zaitsev

Br Br

+ 29% Hofmann

KOtBu
tBuOH

+ 28% Zaitsev 72% Hofmann

203: SN1 Substitution + E1 Elimination EtOH

EtOH

H O

EtOH
H

SN1 product (solvolysis) E1 product

204: E1 Elimination only

3/28
OH

H-OSO3H

OH2

HOSO3
H

Week 2 Mechanisms

CHEM S-20ab

Alex Engler

205.1-2: Grignard Formation & Quenching 206.1: Dichlorocarbene t

Cl Cl Cl Cl C Cl R R' R Cl
Br

Mg

MgBr

MgBr

H2O

Grignard Formation
Cl C Cl

Grignard Quenching
Cl Cl

BuO:

I
I

(+/-)

R'

206.2: Simmons-Smith Reagent: Carbenoid

R'

Zn-Cu
CH2 I

ZnI CH2 R

(+/-)

R'

207.1: Making Alcohols leave with Acid (conc HBr or conc HI) See 201 for 1o alcohols and 203 for 3o alcohols
O O OH Cl S O CH3 R N HO O S OTs

207.2: Making Alcohols good LGs w/ Tosylates

207.3: Making Alcohols good LGs w/ SOCl2

O O N Cl HO S Cl O O O OH S Cl S Cl S O

Cl

+
Cl

Cl

207.4: Making Alcohols good LGs w/ PBr3

OH P Br Br Br PBr2 HO Br O

+ Br

P Br

Br

4/28

Week 3 Mechanisms

CHEM S-20ab

Alex Engler

301: Alcohol Alkoxide

H O H O

302: Thiol Thiolate

H S

OH

305.1: Thiol Disulfide

S S I I S I H S S

OH

305.2: Thiol Sulfide

H S

OH

Br

305.4: Neighboring Participation

S Br H S OH OH2 S

Br

S Br

307.1: Alcohol Ether (1o-1o/2o) 307.2: Alkene Ether (2o-2o)

Hg(OAc)2
NaBH4
OH O

Br

307.3: Alkene (3o) Ether (3o-other)

H
R OH O

sol

5/28

Week 3 Mechanisms

CHEM S-20ab

Alex Engler

308.1: Ether (1o) Dihalide

O H H Br HO Br Br Br Br

H O Cl
H O

Br
Br

Br

H2O

308.2: Ether (3o) Alcohol (1o) + Halide (3o)

Cl
H O Cl

HO

HO

O O H

309.1: Alkene Epoxide (1 step)

R O O H
H2O

+
O

309.2: Alkene Epoxide (2 steps)

O H O O Br Br Br Br Br H O H

OH2

OH

Br

OH
Br

Rac

310.1: Opening of Epoxide in Acid

H3C

OH

sol

H O

CH3

CH3

H
O OH OH OH

310.2: Opening of Epoxide in Base

O CH3 O CH3 O O H OCH3

OH

CH3 O

6/28

Week 3 Mechanisms

CHEM S-20ab

Alex Engler

311: Epoxide C-C bond via Grignard

O BrMg CH3 HO H

OH

312.1: Epoxide Vicinal Diol (anti)

H2O

H O H

OH

OH OH

OH2
OH

312.2: Alkene Vicinal Diol (syn)

O O Os O O O O Os O
CH3 O O O O H

H2O

OH

OH

313: Vicinal Diol Ketone & Aldehyde

OH

HIO4

O I

=
H O

CH3

OH

314.1-2: Alkyne Alkene Halide Geminal Dihalide

C CH H Br C

Br
CH2 Br

Br

Br

Br Br C CH

Br

Br

Br

314.3-4: Alkyne Trans Vicinal Dihalo Alkene Tetrahalo Alkane

Br
H Br

Br
Br

Br

Br Br Br Br Br Br Br Br Br

314.5: Alkyne Enol Aldehyde

H BR2 H C CH BR2 H O

OH
O O

2. H2O2, NaOH

7/28

Week 3 Mechanisms
Hg2+
C CH C

CHEM S-20ab

Alex Engler

314.6: Alkyne Enol Ketone

OH OH Hg Hg Hg2+ CH Hg

H
OH2

H2O

OH2

OH

H
O H O

OH2

316: Alkyne trans-Alkene

H NH2

H NH2

317: Alkyne (terminal) Acetylide C-C bond

C

NH2
CH C C Br

Br

318.1: Benzylic Hydrogen Bromine

H Br

Br

Br

Br

Br

Br

318.2: Allylic/Benzylic Hydrogen Bromine

O

Br

Cl

Br

+
Cl Cl Cl

(NBS)
O

319: Benzylic Hydrogen Carboxylic Acid

H H H O

KMnO4

OH OH

8/28

Week 4 Mechanisms

CHEM S-20ab

Alex Engler

400.1: CrO3 mech: 2o Alcohol Ketone

pyr

pyr

H O O Cr O OH O

OH O O Cr O O

OH O Cr O

proton transfer

400.2: CrO3 mech: 1o Alcohol Aldehyde Carboxylic Acid

H2O
H H O Cr O O O OH O Cr O O OH O O Cr O OH O

H-pyr

HO H

OH

H+ transfer

H3O+

HO

OH2

OH2

HO

OH O

H O

Cr O

H2O H2O
O Cr O O H O O HO O OH Cr O

OH

H+ transfer

+ H3O+ + H2CrO3
OH

401.1: Phenyl Hydrogen Chlorine Cl Cl Cl

Cl Cl H Al Cl Cl Cl Al Cl Cl

solv
H Cl Cl

AlCl4-

401.2: Phenyl Hydrogen Bromine Br Br

Br Br Br H Fe Br Br Fe

Br

Br Br

solv
H Br Br

FeBr4-

401.3: Phenyl Hydrogen Nitro

O

OSO3H OH O N O OH2

N O H H NO2

solv
NO2

N O

9/28

Week 4 Mechanisms

CHEM S-20ab

Alex Engler

401.4: Phenyl Hydrogen Sulfonic Acid

O S O H OSO3H O O S O OH H H SO3H

solv
SO3H

401.5: Friedel-Crafts Alkylation

Cl Cl Al Cl Cl Cl Cl Al H Cl Cl

solv
H

401.6: Friedel-Crafts Acylation

R O O Cl Al Cl R Cl Cl O Cl Al R H R Cl Cl R

solv
H O O

Cl

402.1: Addition-Elimination w/ Aryl Halides

O N O O2N Cl O2N

Cl OH

O2N

OH

OH
O N O O N O

402.2: Elimination-Addition via Benzyne

NH2
NH2 NH2 H Br Br

NH2

NH2

NH2

NH3 NH2

NH3

403.01: Aldehyde/Ketone Cyanohydrin

O

HCN
H

CN

HO

CN

CN

10/28

Week 4 Mechanisms

CHEM S-20ab

Alex Engler

403.02: Ketone Alcohol & C-C via Grignard

MgBr O

OH

H+ w/u

403.03: Aldehyde/Ketone Geminal Diol or HH O ydrate

2

H+

OH

HO

OH2

HO

OH

H2O

403.04: Aldehyde or Ketyone in Base Hemiacetal

OH
HO H O

solv-H

OMe

HO

OMe

OMe HO-H
O O H O O O O OH

403.05 & 403.06: Protecting Ketones and Aldehydes using Acetals

O H2O H OH H O HO OH H H OH O OH HO

H+

OH

HO

H2O H

H+
O

H OH

H OH

transfer
OH OH

solv H+
O O O OH O OH H H H

OH2

OH2

H+ transfer
OH

S.M.
OH

11/28

Week 4 Mechanisms

CHEM S-20ab

Alex Engler

403.07: Aldehyde or Ketone Imine

N

H+

OH

HO

H2O NH2Me

H+ transfer

NHMe

NH2Me
Me

Me

solv

HN

solv:
H N
H
H

403.08: Aldehyde or Ketone Enamine

O H

as above w/ LPP

403.09 & 403.10: Wittig Alkene Synthesis

Ph H H O O PPh3 PPh3 Br PPh3 O H Ph H

Ph3P:

n-Bu:

PPh3

PPh3 Ph

Ph

403.14: Baeyer-Villiger Oxidation

R

RCO3H

O O OH O O R R' R R' RR R' R

OH O O

H+
O

OH R O R' O RR OH

RR O R' O R O OH

:solv
R'

404: Grignard + CO2 Carboxylic Acid O

O MgBr C O O

H+

OH

12/28

Week 4 Mechanisms

CHEM S-20ab

Alex Engler

405.1: Fischer Esterification

O

H+

OH

OH

H+
OH OH OHR

OH

OH

:solv

OH

transfer
OR

OH2

OR

OR

ROH

405.2: Diazomethane Esterification

O O H3C O H2C N N N N OCH3 O

OH

+ N2 (g)

405.3: Esterification with halide in presence of K2CO3

O H3C O I

OH

OCH3

405.4: Acid-cat tert-butyl ester formation

Br OH O O

:solv
O OH O

405.5: Carboxylic Acid Acid Chloride

O S O Cl Cl O

O S Cl O

O S Cl

+ Cl

OH

:solv

OH

OH

OH Cl

Cl

Cl

Cl

405.6: LAH Reduction of Cbx Acid

H O H

Al H

H2 (g)
O H

H O Al H Al H H H H H H H H Al H H O OAlH2 H

OH

H+
OH

w/u

13/28

Week 4 Mechanisms

CHEM S-20ab

Alex Engler

406.1: Transesterification

406.2: Acidic Hydrolysis of Esters

O

H+

OH

OH

H+
OR OH2

OH

OH

:solv

transfer

OR

OR

OHR OH

OH

OH

H2O

406.3: Basic hydrolysis (preferred to acidic)

O O O

-OH
OH

H+
O

-OH
OR

OR OH

workup

OH

406.4: Dry Hydrolysis of tert-butyl ester H+

O H OR Al H H OR H H

OH

+
O OH

O
H

406.5: LAH reduction to primary alcohol

O H O H Al H H H workup H OH O

H+

406.6: Reduction with DIBAL at -78oC aldehyde

Al Al O O

H3O+

H OR OR H

406.7: Grignard Addition to Ester

14/28
Ph O O O O OH

H+
OR Ph OR Ph Ph

workup

Ph

BrMg

Et

BrMg

Et

Week 4 Mechanisms

CHEM S-20ab

Alex Engler

407.1: Acid Chloride with water

OH

OH

OH2

H+
Cl Cl OH2

transfer

Cl OH

OH

OH

OH2
OH2

407.2: Acid Chloride with Alcohols

OH

OH

H+
Cl Cl OHR

transfer

Cl OR

OR

OR

OHR

407.3: Acid Chloride with Amines

OH

H+
Cl H2NR Cl NH2R

OH Cl NHR

pyr

transfer

NHR

NHR

407.4: Acid Chlorides with organozinc reagents

O BrZn Cl

Cl

408.1: Acidic hydrolysis of amides same mech as 406.2

408.2 Basic hydrolysis of amide same mech as 406.3

408.3 Alcoholysis of amide (not very effective)

O R N H H

same mech as 405.1

H Al H H H N H O R H Al H H N H R R N H H R H NR H H Al H H H R H O Al H H H N OAlH2

408.4: LAH reduction of amide

H+ workup
N

15/28

Week 4 Mechanisms

CHEM S-20ab

Alex Engler

409.1: Weinreb amide w/ Grignard addition

MgBr Br O O O CH3 R CH3 CH3 N CH3 R CH3 N N Mg O CH3 R

H3O+

BrMg

409.2: Weinreb amide w/ LAH reduction

H O O N CH3 CH3 H CH3 N O O O CH3 H CH3 N Al

H3O+
O CH3

AlH4

409.3: Formation of Weinreb amides

Cl CH3 O OCH3 HN O O N CH3 CH3

+ pyr

410.1: Acidic Hydrolysis of Nitrile

OH2 OH

Me

Me

NH Me NH

H+ transfer
Me NH2 Me

OH

OH2

H+

H2O

NH2

same mech as before

OH

NH2

410.2: Basic Hydrolysis of Nitrile same mech as 406.3

H H

410.3: Nitrile to Amine via LAH Me

add "H:-"
C N

H+ workup

twice

Me

NH2

16/28

Week 5 Mechanisms
HO HO

CHEM S-20ab

Alex Engler

501: Carbohydrate Saccharide OR Hemiacetal Acetal

HO

HO

HO
OH

H+
O HO

HO O HO

& deprotonate HO
O OH

OH

HO O

HO OH

HO O

HO OH

O O

HO OH

OH2

HO OH

OH

HO OH

OH

502: Strecker Synthesis of Amino Acids H N

H2N NH2 C Ph Ph OH H2N NH2 H2O OH H2N NH3 Ph HO OH H2N OH O

H-NH3 H3N

OH

NH3 H OH

NH2 OH2

NH2

NH

H+ transfer

:sol
Ph OH2 H2N H2N NH2 Ph OH

Ph

Ph

Ph N

Ph NH H2N C

H3N-H
H NH HN C H2N

H2O-H
C

OH2
Ph OH Ph

NH

H+

transfer
Ph O H2N OH

:sol

H+

OH2
Ph Ph

transfer
Ph Ph

503: Forming Peptide bonds with the Coupling Agent DCC

C N R N H R N O R O H2N H N R N H NH2 N R C N N R O O N

Ph

R OH

H+
O

sol:
R

O H

N H

H+
R N H

HO

NH

N R

transfer
O N H

OH

N R O

+
N H N H N H N H

504.1: Protecting an Amine with Boc2O

O

H N
2

O O H N

Me

OH

OH O Me

(Boc)

Boc2O

17/28

Week 5 Mechanisms
O

CHEM S-20ab

Alex Engler

504.2: Deprotecting an Amine with TFA

O H2N OH F3C O Me OH Me

H N

OH

504.3-4: Protecting/Deprotecting Cbx Acid with acidic alcohol / NaOH

Boc N H O

H2N OH Me

MeOH, H+ H2N
OMe Me

NaOH (aq)

H2N OH Me

505: Solid Phase Synthesis

Boc OH

Cs2CO3

Boc N H O

Cl

O N H O

H2N Boc

TFA

O H2N O

O OH N H O O OH N H O

Cmpd A

Cmpd A, DCC

H N Boc N H O

HF

506.1: Keytone to Enol via Enolate in base

H O O

H-OH

OH

OH

OH

enolate

enol

H-OH

506.2: Keytone to Enol in acid

sol: H-sol
H O

H+

OH

OH

OH

:sol

18/28

Week 5 Mechanisms
H+

CHEM S-20ab

Alex Engler

506.3: Ketone in acid to Alpha-halocarbonyl via enol 506.4: Ketone in bOase to saturated AO lpha-Halocarbonyl via enol O
O O

OH H

OH2

OH Br Br

OH

OH2
Br

O Br

Ph Ph H H H Br Br

Ph

OH
O

Ph H Br Br Br Br

Ph Br Br

OH

506.5: Bromoform from Methyl Ketone

Ph O O O OH Ph OH O

CBr3
Ph O

+ HCBr3

Ph

CBr3

Ph

CBr3

HO

507.1: Aldol Reaction in base

O O O H H H H

HO-H

OH

OH

OH

OH

aldol addition intermediate

H H

OH

aldol condensation product

507.2: Aldol Reaction in acid

H+
H

OH H

OH H

OH H

H+
O O OH H

:sol :sol
OH

O OH

O OH

OH O

sol:
H

Aldol condensation
product

H2O

HO

H+

HO

HO

Aldol addition intermediate

19/28

Week 5 Mechanisms

CHEM S-20ab

Alex Engler

508.1: Claisen Condensation

H O O O O OEt O

OEt

OEt

OEt

OEt

OEt O O O O

H+ workup
OEt OEt OEt

stable enolate
O O O O OH O O O

H
O

508.2: Hydrolysis & Decarboxylation of -keto esters 509.1: Alkylation of -dicarbonyl Enolate Ions

OEt

OMe

OMe

OH

OH OH
O

H+ workup
H

OH

OH

OH

H+ +

O C O

EtO H

OEt

EtO

OEt

EtO Br

OEt

OEt

509.2: Alkylation and Decarboxylation

20/28
O Me O H EtO OEt O O

OH

OEt OEt H

OEt

OH Hydrolysis & Decarboxylation

O Me OEt H3C OEt I O O O

Week 5 Mechanisms
O OLi

CHEM S-20ab

Alex Engler

510.1: Slight excess of LDA: Kinetic Lithium Enolate

Li -78oC
H

R2N:

1.1 eq

510.2: Slight deficit of LDA: Thermodynamic Lithium Enolate

O Li O

OLi

R2N:

-78oC
H

0.9 eq
O

511.1: Alkylation at alpha position with LDA (Ester or Nitrile)

O

0.1 eq

0.9 eq
O

0.9 eq

0.1 eq

Li Me-I

LDA -78oC

+ LiI

511.2: Opening Epoxides with LDA

O

OEt

O O O OEt

H+
OEt

HO OEt

workup

:NR2

512.1: ,-unsataturated carbonyls with Grignards

O

Ph-MgBr

Ph

Ph

OH

H+ workup

Ph-MgBr H+ workup kinetic product

Ph Ph

R-Li

O R

512.1: R-Li or LiAlH4 addition: 1,2 addn ONLY

O R OH

thermodynamic product

H+ workup

512.3: 1,4 Conjugate Addition with R2-CuLi R

Li
Cu R R R O O O

H+ workup

21/28

Week 5 Mechanisms

CHEM S-20ab

Alex Engler

512.4: Conjugate additions with NaOH, NaCN (in alcohol solvent), Thiolate (NaSR), or primary and secondary amines Nu: 513: The Michael Reaction
O O O O O
CuLi O

sol-H

512.5: Tandem 1,4 Addition and Alkylation

Br O O

Nu

Nu

2 (+/-)

EtO-H
OEt

OEt H

OEt

+
O

OEt
O

OEt
5

1 2 3 4

514. The Robinson Annulation

O O HO O O O O H Me

OEt

O Me

O Me

O Me

H-OEt
O O

EtO
O

-dicarbonyl
O Me

Michael Acceptor: , unsaturated carbonyl

O O Me

Aldol Condensation

O Me Me

Polycyclic system where new ring has , unsat. carbonyl; 1,5 dicarbonyl

H-OEt

22/28

Week 6 Mechanisms

CHEM S-20ab

Alex Engler

601.1: 1o Amine Synthesis via Azide Reduction

Br

N N N

N N N

H2, Pd
NH2

601.2: 1o Amine Synthesis via Nitrile Reduction

Br C N

1. LiAlH4 2. H+ w/u

NH2

601.3: Aryl Amine Synthesis via Nitro Reduction

HNO3 H2SO4

Sn HCl
O2N H2N

601.4: 2o/3o Amine Synthesis via Amide Reduction See 408.4

H2 N H N

601.5: 2o/3o Amine Synthesis via Reductive Amination 602: The Mannich Reaction: Making -amino carbonyls Ketone/Aldehyde H
23/28
Aldehyde H+
O OH HO H O

H+

OH

HO

H+ transfer

H2O

HN

H2N HN H H B H C N

H+

OH

OH

iminium intermediate
HN OH

:sol
HN

:sol
H

enol intermediate

H2 N

H2O

H N

H H2N

HN

1o or 2o amine

Week 6 Mechanisms

CHEM S-20ab

Alex Engler

603.1: Beckmann Rearrangement (1,2-Alkyl Migration to Nitrogen) OH OH sol: H+

N OH OH O

H+

OH

H2N OH

HO

H2N

OH

H2O

HN

OH

HN

H+

H+ transfer oxime intermediate end step 1

ketone (cyclic or acyclic)

OH2

:sol OH2
N N OH2 N N

:sol

rearrangement step

HN

HN

tautomer of amide "enol form"

O O Cl

amide

603.2: Curtius Rearrangement (1,2-Alkyl Migration to Nitrogen)

O O N N Cl N N N H N Ph OH Ph N N N Ph N N N Ph N Ph C N O

Ph

rearrangement step

H+
OMe Ph N OMe N OHMe

H N Ph O

N Ph C O

OMe

H+ transfer

Ph O

:sol

OH

MeOH

amide tautomer

603.3: Hofmann Rearrangement (1,2-Alkyl Migration to Nitrogen)

O H N NH O O Br N N O Br O C N

1o amide

OH

Br

Br

OH

rearrangement step HO-H

HO-H
NH

H N

H N

N C O

O NH2

OH

OH

HO
OH

"amide enolate" 1o amine

24/28

Week 6 Mechanisms
O N

CHEM S-20ab

Alex Engler

604.1: Synthesis of Aryl Diazonium Salts

N N N N OH2 O

H+

O N

OH

H+

O N

OH2

NH2

H2 N N

H+ t/f H+
H N N H N N

OH

OH

transfer

N2 N2

Cl

604.2-4: Reactions of Aryl Diazonium Salts

X

CuIX
H

O P H OH

(X = Cl, Br, I, CN)

N2

OH

H2O

605.1: Diels-Alder Reaction

OMe

NC

OMe CN CN

H CN

OMe

(+/-)

OMe

OMe

(+/-)

OMe

CN "trans" w/ CN, like SM OMe "cis" w/ OMe, like SM

"Endo" diastereomer "ortho" isomer, not "meta"

605.2: Suprafacial cycloaddition

6 e

1 >

> h

NOTE: the UV light excites an electron in the orbital of one cyclopentene into the orbital, allowing suprafacial cycloaddition. h

4 eO

605.3: Antarafacial cycloaddition

O C O C CH2 O O C CH2 CH2

CH2

C O

CH2 C CH2

C CH2

25/28

Week 6 Mechanisms
HOMO: 2 6 e

CHEM S-20ab

Alex Engler

606.1: Disrotatory Electrocyclic Opening/Closing

H3C CH3 CH3 CH3 CH3 CH3

HOMO*: 2 4 eCH3 h
CH3 CH3 CH3 CH3 H CH3

CH3

CH3 H

H3C

CH3

(+/-)

CH3

606.2: Conrotary Electrocyclic Opening/Closing

HOMO: 3 8 e
CH3 CH3

HOMO: 1 4 eCH3

CH3

CH3

CH3

CH3

CH3

CH3

(+/-)
CH3 CH3

H CH3

CH3 CH3

CH3 H

607.1: [1,n] Sigmatropic Rearrangement

H3C H H3C

5 p orbitals, 6 eHOMO: 2 Suprafacial H+

H

7 p orbitals, 8 eHOMO: 3 Antarafacial D+

H3C H

D CH3 D CH3

H CH3

CH3

607.2: The Cope Rearrangement: [3,3] Sigmatropic Rearrangements

1 2 3

LUMO of "cation": 1 HOMO of "anion": 1

2 1

2 3 1

3 2 2 3 1 3 1 1

6 eSuprafacial

2 3

6 5

6 5

6 5

6 5

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Week 6 Mechanisms
6 e-; Suprafacial

CHEM S-20ab

Alex Engler

607.3: The Claisen Rearrangement: [3,3] Sigmatropic Rearrangements

OH O CO2

6 e-; Suprafacial

CO2 O2C

O O CO2 OH

608.1: The Thiamine Cofactor (TPP): Turning an -decarboxylation into a -decarboxyliation

H-enz

RN

H OH S O RN RN O S O OH

O O S H

H-enz

enz:

RN

Decarboxylation Product: Aldehyde

-ketoacid
S

TPP: Thiamine

- 608.2: NADH Cofactor a source of HR R

H-enz
N N

+ HN 3
H O H H

H2N

+
OH O H

608.3: HSCoA Cofactor: Transesterification or Retro-Claisen

NH3 O NH3 O O O CoAS O H3N OH NH3

aldehyde

NADH

NAD+

ethanol

H-enz

enz-H
O O HO SCoA

H-enz
O

+ :enz

enz:

Acetyl CoA

enz:

H-SCoA

Glycine

608.4: Lipoamide Cofactor: Addition of a Leaving Group

HO S O

enz-H
R N

O O R N

OH O R N

enz-H
OH S S

lipoamide
R

TPP :enz
SCoA R O

:enz H-enz
R OH R N S S SH S SH S

SH

H-enz
O

enz:
SH SH

H-SCoA

+
SCoA R

Acetyl CoA

27/28

Week 6 Mechanisms

CHEM S-20ab

Alex Engler

608.5: ATP Cofactor:

O O Me OH

:enz
P P P A O

Me

O P

Me

28/28