SUMMARY MECHANISMS

O F OFM E C H A N I S M S
] SUMMARY ]
Nucleophilic Addition to Aldehydes and Ketones Under Basic Conditions
Generalized nucleophilic addition to an aldehyde or ketone:

A H − Protonation during H
O workup O
O
(in most reactions) −
+ Nu− + A
R′ Nu or by protic solvents R′ Nu
R′ R″(H)
R″(H) R″(H)
Aldehyde or
ketone Nucleophile Tetrahedral intermediate Product

−
H
O O
Examples: −
H Alcohol (reduction)
R′ H R′ H
Hydride [e.g., from
R″(H) R″(H)
NaBH4 or LiAlH4 (LAH)]
−
H
Li+ O O
Li R Alcohol (with C C bond formation)
R′ R R′ R
Alkyllithium
R″(H) R″(H)
−
H
XMg+ O O
XMg R Alcohol (with C C bond formation)
R′ R R′ R
Grignard reagent
R″(H) R″(H)
H
−
O O
− Alkynyl alcohol (C C bond formation)
C C R
R′ C R′ C
Alkynide anion R″(H) C R″(H) C
R R
−
H
O O
− Cyanohydrin
C N
R′ C R′ C
Cyanide R″(H) N R″(H) N
Summary of Mechanisms
667
 668
Chapter 15

] S U M M A R Y O F M E C H A N I S M S ]
Nucleophilic Addition to Aldehydes and Ketones Under Basic Conditions

Generalized nucleophilic addition to an aldehyde or ketone:

A H − Protonation during H
O workup O
O
(in most reactions) −
+ Nu− + A
R′ Nu or by protic solvents R′ Nu
R′ R″(H)
R″(H) R″(H)
Aldehyde or
ketone Nucleophile Tetrahedral Intermediate Product

+ R′ R2
P(C6H5)3 O P(C6H5)3
Examples − Oxaphosphetane Wittig preparation of alkenes
R2 R′ R2
(continued): intermediate (with loss of triphenylphosphine
R″(H) R1
R1 R″(H) R1 oxide [(C6H5)3PO])
Aldehydes and Ketones I. Nucleophilic Addition to the C

(plus diastereomer)
Phosphorus ylide

b -Hydroxy and a,b -unsaturated

− − H carbonyl compounds
O O O O O O R′ O
­ arbonyl Group

−
R3 R3 R4 R′ R4 R′
R4 R4 (H)R″ R4
R″(H) R″(H)
H R3 H R3 H −
H A R3
Enolate (see Chapter 18)
 ]SYNTHETIC C O N N E C T I O N S ]
Some Synthetic Connections of Aldehydes, Ketones, and Other Functional Groups

Clockwise from center, O OH ROH, OR

bottom: cat. HA

I. Preparation of aldehydes R′ Cl R′ OR H2O, R′ OR

and ketones: (1) ArH, AlCl3; ROH, R′′(H) cat. HA R′′(H)
R′ R′′ (2) HOH cat. HA
• Nitrile, ester, acyl (leads to R′′=Ar)
R′ C N
halide reduction H2O, SR H2, H
R′′ R′ (1) R′′MgBr cat. HA Raney Ni
• Alcohol oxidation (1) O3 or R′′Li
• Ozonolysis (2) Me2S (2) H3O+ R′ SR R′ H
• Friedel–Crafts (products depend RSH (2 equiv.), R′′(H) R′′(H)
acylation on R groups) cat. HA
• Grignard with nitrile
OH H2O,
• Acetal and hemiacetal O cat. HA
hydrolysis H2CrO4 or KMnO4
NH2NH2,HO– OH
R′ R′′ ∆
R′ R"
R′ C
NaBH4; or (1) LAH; (2) H2O (1) RC C− R′′(H) C
R
(2) H3O+

R′ OH PCC O OH
−
R′ H (1) NC
II. Reactions of aldehydes (2) H3O+ R′ C
and ketones: (1) LiAlH(O-t-Bu)3 R′′(H) N
(2) H2O
• Hemiacetal and O
acetal formation 3 4
(1) CHR R Br, (C6H5)3P
• Thioacetal formation R′ Cl (1) DIBAL-H (2) RLi (as strong base)
and reduction (2) H2O
• Wolff– Kishner R2NH,
SOCl2 (1) DIBAL-H RNH2,
cat. HA R′ R3
reduction RCO3H cat. HA
O (2) H2O
• Alkynide anion addition
R R
• Nitrile addition O R N R′′(H) R4
(cyanohydrin formation) R′ OR′′ R′ C N
O N
• Wittig synthesis of alkenes
R′ OH (E ) and (Z )
• Enamine synthesis R′′(H)
• Baeyer–Villiger oxidation R′ OR′′(H) R′ R′′(H) (when R′ bore a
• Imine synthesis hydrogen for removal)
• Reduction to alcohols
(left, center)
Synthetic Connections
669