Page 425 - Advanced Organic Chemistry Part B - Reactions & Synthesis

398 The products are liberated by hydrolysis of the aluminum alkoxide at the end of
the reaction. Lithium aluminum hydride reduction of esters to alcohols involves an
CHAPTER 5 elimination step in addition to hydride transfers.
Reduction of
Carbon-Carbon Multiple M +
Bonds, Carbonyl M + –
Groups, and Other – O AlH 3 O
Functional Groups O AlH 3 –
RC OR RCH + ROAlH 3
RC H
H
OR
M +
–
O AlH OR – H O
2
RCH O AlH OR 2 RCH OH
RC H 2 2 2
H
Amides are reduced to amines because the nitrogen is a poorer leaving group
than oxygen at the intermediate stage of the reduction. Primary and secondary amides
are rapidly deprotonated by the strongly basic LiAlH , so the addition step involves
4
the conjugate base.

M + –
– O AlH 3 R H
O AlH 3 – H O
2
RCH C H RCH NAlH O – RCH NH 2
2
2
2
RC H
NH HN AlH O – H
2
–
NH
–
Reduction of amides by LiAlH is an important method for the synthesis of amines.
4
LiAlH 4
CON(CH ) CH N(CH )
3 2
3 2
2
ether
35°C, 15 h 88%
Ref. 61
CH 3 LiAlH 4 CH 3
N O THF N
CH 3 CH 3
H 65°C, 8 h H
67–79%
Ref. 62
Several factors affect the reactivity of the boron and aluminum hydrides, including
the metal cation present and the ligands, in addition to hydride, in the complex hydride.
Some of these effects can be illustrated by considering the reactivity of ketones
and aldehydes toward various hydride transfer reagents. Comparison of LiAlH and
4
63
NaAlH has shown the former to be more reactive, which is attributed to the greater
4
61 A. C. Cope and E. Ciganek, Org. Synth., IV, 339 (1963).
62 R. B. Moffett, Org. Synth., IV, 354 (1963).
63
E. C. Ashby and J. R. Boone, J. Am. Chem. Soc., 98, 5524 (1976); J. S. Cha and H. C. Brown,
J. Org. Chem., 58, 4727 (1993).