Page 150 - Advanced Organic Chemistry Part B - Reactions & Synthesis

122 Crimmins and co-workers have developed N-acyloxazolidinethiones as chiral
auxiliaries. These reagents show excellent 2,3-syn diastereoselectivity and enantio-
CHAPTER 2
selectivity in additions to aldehydes. The titanium enolates are prepared using TiCl ,
4
Reactions of Carbon with (−)-sparteine being a particularly effective base. 141
Nucleophiles with
Carbonyl Compounds
CH OH CH 3
S O 3 S O
TiCl 4 CH 3
O N O CH O N CH 3
(–)-sparteine CH CH 3 83%
3
CH Ph CH Ph > 98:2
2
2
The facial selectivity of these compounds is also dependent on the amount of TiCl 4
that is used. With two equivalents, the facial selectivity is reversed. This reversal is
also achieved by adding AgSbF . It was suggested that the excess reagent or the silver
6
−
salt removes a Cl from the titanium coordination sphere and promotes chelation with
the thione sulfur. 142 This changes the facial selectivity of the enolate by causing a
reorientation of the oxazolidinethione ring. The greater affinity of titanium for sulfur
over oxygen makes the oxazolidinethiones particularly effective in these circumstances.
The increased tendency for chelation has been observed with other chiral auxiliaries
having thione groups. 143

O
O CH Ph
S O OH PhCH 2 S N 2 S O OH
N S
3
O N R Cl Ti O R Cl Ti O O N R
4
O O
CH 3 CH
CH Ph CH 3 R CH 3 3
2
CH 2 Ph
normal transition structure chelated transition structure
A related effect is noted with -alkoxyacyl derivatives. These compounds give
mainly the anti adducts when a second equivalent of TiCl is added prior to the
4
aldehyde. 144 The anti addition is believe to occur through a TS in which the alkoxy
oxygen is chelated. In the absence of excess TiCl , a nonchelated cyclic TS accounts
4
for the observed syn selectivity.

S O 1) TiCl , S O OH
4
OR (–)-sparteine
O N O N R
2) TiCl 4 OR
CH Ph 3) RCH O CH Ph
2
2

141 M. T. Crimmins and B. W. King, J. Am. Chem. Soc., 120, 9084 (1998); M. T. Crimmins, B. W. King,
E. A. Tabet, and C. Chaudhary, J. Org. Chem., 66, 894 (2001); M. T. Crimmins and J. She, Synlett,
1371 (2004).
142
M. T. Crimmins, B. W. King, and E. A. Tabet, J. Am. Chem. Soc., 119, 7883 (1997).
143 T. H. Yan, C. W. Tan, H. C. Lee, H. C. Lo, and T. Y. Huang, J. Am. Chem. Soc., 115, 2613 (1993).
144
M. T. Crimmins and P. J. McDougall, Org. Lett., 5, 591 (2003).