Synthesis of P-Stereogenic Compounds via Kinetic Deprotonation and Dynamic Thermodynamic Resolution of Phosphine Sulfides: Opposite Sense of Induction Using (−)-Sparteine

详细信息    查看全文

• 作者：Jonathan J. Gammon ; Viktoria H. Gessner ; Greg R. Barker ; Johan Granander ; Adrian C. Whitwood ; Carsten Strohmann ; Peter O&#8217 ; Brien ; Brian Kelly
• 刊名：Journal of the American Chemical Society
• 出版年：2010
• 出版时间：October 6, 2010
• 年：2010
• 卷：132
• 期：39
• 页码：13922-13927
• 全文大小：319K
• 年卷期：v.132,no.39(October 6, 2010)
• ISSN：1520-5126

文摘

A systematic study of the asymmetric deprotonation of a dimethyl-substituted phosphine sulfide using organolithium bases in the presence of (−)-sparteine has been carried out. Use of nBuLi and (−)-sparteine in Et₂O at −78 °C gave trapped adducts in 88:12 er via a kinetically controlled process that was successfully predicted using a computational approach at the B3LYP/6-31+G(d) level. This initial kinetic enantioselectivity could be enhanced up to 97:3 er by trapping the lithiated intermediate with a prochiral electrophile (e.g., pivaldehyde or tBuPCl₂). In addition, it was found that the R_P and S_P stereoisomers of the lithiated methylphosphine sulfide could interconvert at temperatures above 0 °C. Such interconversion is unprecedented and differs from the configurational instability of organolithiums that are stereogenic at a lithiated carbon atom. The major, thermodynamically preferred diastereomeric (−)-sparteine-complexed lithated phosphine sulfide was investigated by X-ray crystallography and computational methods at the B3LYP/6-31+G(d) level. Through the interconversion of the R_P and S_P stereoisomers of the lithiated methylphosphine sulfide, a novel dynamic thermodynamic resolution of a racemic lithiated phosphine sulfide has been developed. Thus, the phosphine sulfide was lithiated with nBuLi, and then (−)-sparteine was added. After equilibration at 0 °C for 3 h, electrophilic trapping generated an adduct in 81:19 er with the configuration opposite to that obtained under kinetic control. Thus, the methodology provides access to P-stereogenic compounds with the opposite sense of induction using (−)-sparteine as the ligand simply by changing the reaction conditions (kinetic or thermodynamic control).