Asymmetric deprotonation adjacent

The asymmetric deprotonation can be advantageously coupled with intramolecular cyclocarbolithiations . (E)- and (Z)-6-phenylhex-5-enyl carbamates 55 are Hthiated by s-BuLi/(—)-sparteine adjacent to the carbamoyloxy group (equation 13). The intermediates... 

As Beak and coworkers have established several years ago, A-rert-butoxycarbonyla-mines are sufficiently acidic to be deprotonated adjacent to the nitrogen atom . When applying 5-BuLi/(—(-sparteine (11) to A-Boc-pyrrolidine, asymmetric deprotonation (149), onepro-S-H is removed with high selectivity, furnishing the configurationally stable 2-lithio derivative 150 which was trapped with several electrophiles to form the optically active substitution products 151 (equation 33) A prescription in Organic Syntheses is... 

The formation of asymmetric carbon-carbon and carbon-heteroatom bonds by lithiation-substitution at a carbon adjacent to nitrogen can be accomplished by deprotonations or des-tannylations, followed by reaction with electrophiles. Apphcations of these sequences for amine elaboration are summarized for reactions controlled by chiral hgands and chiral auxiliaries. Notable features include syntheses of alkaloids, the ability to make both enantiomers with a single chiral ligand and diastereoselective and enantioselective conjugate additions with benzylic and allylic lithiation intermediates. The sequences are classified, where information is available, in terms of stereocontrol in the lithiation or substitution step. 

The direct deprotonative approaches with an enantioenriched ligand from a pro chiral reactant are synthetically most convenient however, the tin-lithiiun exchange is able to provide more diverse intermediates. Both approaches have been used to achieve asymmetric bond formations at carbons adjacent to nitrogen. 

Since benzyUithium compounds having no adjacent heteroatom are configurationally labile [93], their enantioselective reactions may proceed through an asymmetric substitution pathway. In 1971, Nozaki and coworkers commented in the first enantioselective reaction of benzyllithiiun compounds that the enantiomeric ratio of organolithium compounds might be influenced by a chiral additive [94]. Deprotonation of ethylbenzene was performed with n-BuLi-(-)-sparteine at 70°C, followed by carboxylation at -65°C [Eq. (39)]. 

Another classic in asymmetric synthesis is Oppolzer s sultam 91 [48], and various JV-acyl derivatives 92 were used - inter alia - for diastereoselective alkylations. Early attempts for enolate generation from amides 92 were plagued by competing deprotonation at carbon 10, adjacent to the sulfonyl group, but regioselective metallation at the a-carbonyl position was achieved by treatment with -butyllithium, LICA, or NaHMDS. The method is applicable not only to the sultam derived from propionic acid 92 (R = Me) but also to substituted and... 

---