Page 98 - Advanced Organic Chemistry Part B - Reactions & Synthesis

70 Table 2.1. Diastereoselectivity of Addition of Lithium Enolates to
Benzaldehyde
CHAPTER 2
OLi OLi
Reactions of Carbon OH O OH O
Nucleophiles with + 1 PhCH O
Carbonyl Compounds R 1 R +
Ph R 1 Ph R 1
Z-enolate E-enolate
CH 3 CH 3
2,3-syn 2,3-anti
R 1 Z:E ratio syn:anti ratio
H 100 0 50 50
H 0 100 65 35
30 70 64 36
C 2 H 5
66 34 77 23
C 2 H 5
CH 3 2 CH >98:2 90 10
CH 3 2 CH 0 100 45 55
CH 3 3 C >98:2 >98:2
1-Adamantyl >98:2 >98:2
>98:2 88 12
C 6 H 5
Mesityl 8 92 8 92
Mesityl 87 13 88 12
a. From C. H. Heathcock, in Asymmetric Synthesis, Vol. 3, J. D. Morrison, ed., Academic Press,
New York, 1984, Chap. 2.

8
kinetic enolization. The precise mechanism of this effect is still a matter of investi-
gation, but it is probably due to an aggregate species containing bromide acting as the
base (see Section 1.1.1). 9

E:Z Stereoselectivity

LDA LiTMP LiTMP + LiBr
O
CH CH CCH CH 3 3.3:1 5:1 50:1
2
2
3
O
(CH ) CHCCH CH 3 1.7:1 2:1 21:1
2
3 2
O
1: >50 1: >20 1:>20
(CH ) CCCH CH 3
3 3
2
Other changes in deprotonation conditions can influence enolate composition.
Relatively weakly basic lithium anilides, specifically lithium 2,4,6-trichloroanilide
and lithium diphenylamide, give high Z:E ratios. 10 Lithio 1,1,3,3-tetramethyl-1,3-
diphenyldisilylamide is also reported to favor the Z-enolate. 11 On the other hand,
lithium N-trimethylsilyl-iso-propylamide and lithium N-trimethylsilyl-tert-butylamide
give selectivity for the E-enolate 12 (see Scheme 1.1).

8 P. L. Hall, J. H. Gilchrist, and D. B. Collum, J. Am. Chem. Soc., 113, 9571 (1991).
9
F. S. Mair, W. Clegg, and P. A. O’Neil, J. Am. Chem. Soc., 115, 3388 (1993).
10
L. Xie, K. Vanlandeghem, K. M. Isenberger, and C. Bernier, J. Org. Chem., 68, 641 (2003).
11 S. Masamune, J. W. Ellingboe, and W. Choy, J. Am. Chem. Soc., 104, 5526 (1982).
12
L. Xie, K. M. Isenberger, G. Held, and L. M. Dahl, J. Org. Chem., 62, 7516 (1997).