Page 431 - Advanced Organic Chemistry Part B - Reactions & Synthesis

404 NaBH(OAc) 3
R C O + HNR′ 2 R CHNR′ 2
2
2
CHAPTER 5
PhCH CHCO CH + CH (CH ) CH O NaBH(OAc) PhCH CHCO CH
Reduction of 2 2 3 3 2 4 3 2 2 3
Carbon-Carbon Multiple + – NH(CH ) CH
3
Bonds, Carbonyl NH Cl 2 5 3 79%
Groups, and Other
Functional Groups
This method was used in a large-scale synthesis of 1-benzyl-3-methylamino-4-
methylpiperidine. 95
CH
CH 3 3
O
NHCH 3
1) CH NH 2
3
N 2) NaBH 4 N 92% yield
CH CO H
2
3
CH Ph CH Ph on 35 kg scale
2
86:14 cis:trans
2
Zinc borohydride has been found to effect very efficient reductive amination in
the presence of silica. The amine and carbonyl compound are mixed with silica and the
powder is then treated with a solution of Zn BH . Excellent yields are also obtained
4 2
for unsaturated aldehydes and ketones. 96
CH 3 CH 3
CH 3 CH 3
1) SiO 2
N NH
O +H 2
2) Zn(BH )
4 2
CH 3 CH 3 80%
Aromatic aldehydes can be reductively aminated with the combination
Zn BH -ZnCl , 97 and the ZnCl assists in imine formation.
2
2
4 2
1) ZnCl 2
F CH O + H N F CH 2 N
2) Zn(BH )
4 2
77%
Amides are usually reduced to amines using LiAlH . Amides require vigorous
4
reaction conditions for reduction by LiAlH , so that little selectivity can be achieved
4
with this reagent. Diborane is also a useful reagent for reducing amides. Tertiary and
secondary amides are easily reduced, but primary amides react only slowly. 98 The
electrophilicity of borane is involved in the reduction of amides. The boron complexes
at the carbonyl oxygen, enhancing the reactivity of the carbonyl center.

95
D. H. B. Ripin, S. Abele, W. Cai, T. Blumenkopf, J. M. Casavant, J. L. Doty, M. Flanagan, C. Koecher,
K. W. Laue, K. McCarthy, C. Meltz, M. Munchoff, K. Pouwer, B. Shah, J. Sun, J. Teixera, T. Vries,
D. A. Whipple, and G. Wilcox, Org. Proc. Res. Dev., 7, 115 (2003).
96
B. C. Ranu, A. Majee, and A. Sarkar, J. Org. Chem., 63, 370 (1998).
97 S. Bhattacharyya, A. Chatterjee, and J. S. Williamson, Synth. Commun., 27, 4265 (1997).
98
H. C. Brown and P. Heim, J. Org. Chem., 38, 912 (1973).