Page 132 - Advanced Organic Chemistry Part B - Reactions & Synthesis

104 (CH ) C TMS
3 3
OLi H O O OH
) C
CHAPTER 2 (CH ) C CH 3 Li (CH 3 3 R
3 3
Reactions of Carbon + RCH O H H O
Nucleophiles with OTMS CH 3 TBSO CH 3
Carbonyl Compounds
R O major
R 2,2 ′-anti:syn
i-Pr > 95:5
t-Bu > 95:5
Ph > 95:5
PhCH OCH 2 > 95:5
2

The corresponding di-n-butylboron enolate gives the 2,2 -syn adduct. The nonchelating
boron is thought to react through a TS in which the conformation of the substituent is
controlled by a dipolar effect.
The E-titanium enolate was prepared by deprotonation with TMP-MgBr, followed
by reaction with i-PrO TiCl in the presence of HMPA. The TS for addition is also
3

dominated by a polar effect and gives and 2,2 -anti product.
H
1) TMPMgBr TBDMSO
3 3
O 2) HMPA H C(CH ) O OH
(i PrO) TiCl ) C
) C 3 4 Ti(Oi-Pr) 3 (CH 3 3
(CH 3 3 CH 3 R R
3) RCH O CH O
3
OTBDMS O TBDMSO CH 3
H
An indication of the relative effectiveness of oxygen substituent in promoting
chelation of lithium enolates is found in the enolates 3a–d. The order of preference
for the chelation-controlled product is CH OCH O > TMSO > PhCH O > TBDMSO,
3
2
2
with the nonchelation product favored for TBDMSO. 107
OR CH3 OR CH3 OR
1) LDA (CH ) 2 CH (CH ) CH
3 2
3
CH 3 TMEDA
O OH O + OH O
) CHCH
2) (CH 3 2 O
2′,3-anti 2′,3-syn
chelation-control
CH 3
R
O
CH(CH )
3 2
3
Li O 3a CH OCH 2 93:7
b 75:25
H PhCH 2
O c TMS 88:12
R d TBDMS 24:76
chelated TS
107
C. Siegel and E. R. Thornton, Tetrahedron Lett., 27, 457 (1986); A Choudhury and E. R. Thornton,
Tetrahedron Lett., 34, 2221 (1993).