Alkyl carbamates asymmetric deprotonation

Coldham and coworkers have shown that the asymmetric deprotonation protocol can be used to regioselectively alkylate the 5-position of imidazolidines (Scheme 35). The process is used as part of a sequence that results in asymmetric alkylation of 1,2-diamines with high stereoselectivity. The yields are limited, in this case, by the barrier to rotation around the carbamate C—N bond. Thus, only the amide rotamer having the carbonyl group syn to C-5 of the heterocycle is deprotonated. There are several examples in this review where this limitation is possible whether it is a factor or not may depend on the temperature at which amide bond rotation occurs versus the stability of the organolithium compound. In this case, the barrier to amide bond rotation was determined as 16.6 kcalmoD at 60 °C. 

The first successful examples for asymmetric deprotonation by alkyllithium/(—)-sparte-ine (11) utilizing O-allyl and O-alkyl carbamates were published in 1989-1990 by Hoppe and coworkers °. Later, in 1991, Kerrick and Beak contributed the application of this method to Ai-Boc-pyrrolidine" (Sections II.D.l). 

The asymmetric (—)-sparteine-mediated deprotonation of alkyl carbamates was unprecedented until discovered in 1990 °. For the first time, protected 1-alkanols could be transformed generally to the corresponding carbanionic species by a simple deprotonation protocol. Moreover, an efficient differentiation between enantiotopic protons in the substrate took place and the extent of stereoselection could be stored in a chiral ion pair, bearing the chiral information at the carbanionic centre. 

The asymmetric deprotonation of carbamates can be extended beyond pyrrolidines. Beak, for example, disclosed metalation of benzylamine 60 and alkylation of the resulting carbanion with methyl triflate to furnish 61 in 98 % ee (Scheme 13.10) [55]. Subsequent proton abstraction from 61 was effected with u-BuLi in the presence of TMEDA, followed by stereospecific alkylation with allyl triflate. Following removal of the p-methoxybenzyl group (CAN), the trisubstituted carbamate 62 was isolated in 97 % ee. 

It is especially remarkable that optically active homoaldoi adducts can be obtained when enantiomeri-cally pure 2-alkenyl carbamates (47 R = alkyl) are employed. Apparently the deprotonation occurs with retention of configuration and leads to configurationally stable liAium derivatives, which, after metal exchange with Ti(OPr )4, again with retention, add to aldehydes with efficient 1,3-chirality transfer coupled with enantiofacial differentiation at the carbonyl group, indicating a rigid six-membered transition state. Recently even an asymmetric homoaldoi reaction by enantioselective lithiation of prochiral primary alkenyl carbamates in the presence of (-)-sparteine was reported. ... 

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