Chiral phosphoramide-catalyzed aldol additions of ketone trichlorosilyl enolates. Mechanistic aspects

被引:55
作者
Denmark, SE [1 ]
Pham, SM [1 ]
Stavenger, RA [1 ]
Su, XP [1 ]
Wong, KT [1 ]
Nishigaichi, Y [1 ]
机构
[1] Univ Illinois, Roger Adams Lab, Dept Chem, Urbana, IL 61801 USA
关键词
D O I
10.1021/jo060243v
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The mechanism of the catalytic, enantioselective addition of trichlorosilyl enolates to aldehydes has been investigated. Kinetic studies using ReactIR and rapid injection NMR (RINMR) spectroscopy have confirmed the simultaneous operation of dual mechanistic pathways involving either one or two phosphoramides bound to a siliconium ion organizational center. This mechanistic dichotomy was initially postulated on the basis of catalyst loading studies and nonlinear effects studies. This duality explains the difference in reactivity and stereoselectivity of various classes of phosphoramides. Determination of Arrhenius activation parameters revealed that aldol addition occurs through the reversible albeit unfavorable formation of an activated complex, and natural-abundance C-13 NMR kinetic isotope effect (KIE) studies have determined that the turnover limiting step is the aldol addition. A thorough examination of a range of phosphoramides has established empirical structure-activity selectivity relationships. In addition, the effects of catalyst loading, rate of addition, solvents, and additives have been studied and together allow the formulation of a unified mechanistic picture for the aldol addition.
引用
收藏
页码:3904 / 3922
页数:19
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