Page 138 - Advanced Organic Chemistry Part B - Reactions & Synthesis

110 B(C H ) TBDMSO O TiCl 3
6
11 2
TBDMSO O TBSDMSO O
CH CH 3
CHAPTER 2 (CH ) CH 3
) CH
(CH ) CH 3 2 (CH 3 2
Reactions of Carbon 3 2 CH 8 CH 3
Nucleophiles with CH 3 3 CH 3
Carbonyl Compounds OPMB
O OH
TBSDMSO O OH OPMB TBSDMSO O OPMB
H CH(CH ) 3 2
CH(CH ) (CH ) CH CH(CH ) 3 2
(CH ) CH 3 2 3 2
3 2
CH 3
CH CH 3 CH CH 3 CH 3 CH 3
3 3
A fully matched; >99:1 85% 9a E partially matched; both syn 87:13 81%
TBSDMSO OH OPMB OPMB TBSDMSO OH OPMB
O O O
CH(CH ) CH(CH )
(CH ) CH 3 2 CH(CH 3 2 ) (CH ) CH 3 2
3 2
3 2 H
CH CH
CH 3 CH 3 CH 3 3 3 CH 3
CH 3
B partially matched; >99:1 85% 9b F fully matched;89:11; both syn 86%
OPMB
O OPMB
TBSDMSO OPMB TBSDMSO O OH
O OH
)
H CH(CH )
CH(CH 3 2
(CH 3 ) 2 CH CH(CH ) 3 2 (CH ) CH 3 2
3 2
CH CH 3 CH
CH 3 CH CH 3 3 CH 3
3 3
G fully mis-matched; 37:35:28; two major 79%
C partially matched; 81:19; both anti 9c
stereoisomers both syn plus a third isomer
OPMB
O
TBSDMSO OPMB
O OH TBSDMSO OH OPMB
3 2
H CH(CH ) O
CH(CH )
(CH ) CH 3 2
3 2 CH(CH )
CH 3 (CH ) CH 3 2
CH 3 2
CH 3 3 CH 3
CH 3 CH
CH 3
3
D fully mis-matched; 65:25:10; two major 9d H partially matched; 92:8; both syn 85%
stereoisomers both anti plus a third isomer
The results for the boron enolates show that when the aldehyde and enolate centers
are matched the diastereoselectivity is high (Cases A and B). In Case C, the enolate
is matched with respect to the -alkoxy group but mismatched with the -methyl
group. The result is an 81:19 dominance of the anti-Felkin product. For the titanium
enolates, Cases E and F correspond to a matched relationship with the -stereocenter.
Case G is fully mismatched and shows little selectivity. In Case H, the matched
relationship between the enolate and the -alkoxy group overrides the -methyl effect
and a 2,3-syn (Felkin) product is formed. The corresponding selectivity ratios have
also been determined for the lithium enolates. 118 Comparison with the boron enolates
shows that although the stereoselectivity of the fully matched system is higher with
the boron enolate, in the mismatched cases for the lithium enolate, the aldehyde
bias overrides the enolate bias and gives modest selectivity for the alternative anti
isomer.
In general, BF -catalyzed Mukaiyama reactions lack a cyclic organization because
3
of the maximum coordination of four for boron. In these circumstances, the reactions
show a preference for the Felkin type of approach and exhibit a preference for syn
stereoselectivity that is independent of silyl enol ether structure. 119
118 D. A. Evans, M. G. Yang, M. J. Dart, and J. L. Duffy, Tetrahedron Lett., 37, 1957 (1996).
119
D. A. Evans, M. G. Yang, M. J. Dart, J. L. Duffy, and A. S. Kim, J. Am. Chem. Soc., 117, 9598 (1995).