Chiral Carbanions by Deprotonation

One of the most impressive advances in this discipline can be found in Beak s work involving the metalation and asymmetric transformations of pyrrolidine derivatives [54]. Deprotonation of N-Boc-pyrrolidines 58 in the presence of sparteine (36) and treatment with a variety of electrophiles give access to a host of substituted derivatives in high optical purity, such as 59 (95% ee, Equation 5). 

In addition to the various tactics that have been ingeniously devised, there has been intense activity in the search for chiral diamines that can be employed in similar manner to sparteine but can furnish products in the enantiomeric series. Although enf-sparteine is itself a natural product, it is unfortunately not available in preparatively useful quantities, neither by isolation nor by synthesis, which is a necessary prerequisite for a stoichiometric additive [20]. The identification of other suitable chiral diamines as alternatives to ewt-sparteine has proven elusive, with one notable exception. In 2002, 

Beak reported some remarkable observations that not only provided mechanistic insight, but also represented useful strategies for the preparative application of asymmetric organolithium chemistry (Equation 8) [60], Treatment of 80 with sec-BuLi at -25 °C thus led to the formation of the putative organolithium species 81. When (-)-sparteine (36) was added at -25 °C and the mixture was allowed to age for 45 min, subsequent addition of TMSCl afforded 82 in 72% yield and 90% ee. Under otherwise identical conditions, albeit with a reduced aging period of 5 min, the product 82 was obtained in only 39 % ee. If the solution of anion 81 was cooled to -78 °C before addition of sparteine, addition of TMSCl resulted in 52% yield and only 21% ee. These observations implicate the operation of an intricate interplay between kinetic and thermodynamic processes. 

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