Asymmetric deprotonation -sparteine

Several stress tests were performed before scale-up. If the asymmetric deprotonation of 19 was carried out at -55 to -45 °C instead of-70 to -60 °C, product 5 from the coupling reaction was obtained in a significantly lower 85% ee although the yield was not affected (83%). An overcharge of (-)-sparteine provided only a marginal improvement in the ee of product 5 for example, l.lequiv of sparteine provided a 93% ee while 0.90 equiv of sparteine gave a slightly eroded 89% ee. 

Asymmetric deprotonation of the achiral oxazolidine iV-Boc-4,4-dimethyl-l,3-oxazolidine with s-BuLi-(—)-sparteine affords a lithium derivative that adds unselectively to aldehydes. However, the transmetalation from lithium to magnesium, and addition of the resulting Grignard to benzaldehyde occurs with 90% diastereoselectivity and 93% enantioselectivity. The authors speculate that deprotonation and lithiation occur stereoselectively to give the R organolithium compound, and subsequent transmetalation and addition to benzaldehyde proceed with retention (Scheme 40). 

The chiral base i-BuLi/(—)-sparteine enantioselectively deprotonates the benzylic position of Ai-Boc-3-chloropropyl carbamates, which then cyclize to yield 2-substituted pyrrolidines with enantiomeric ratios greater than 90 10 (Scheme 63). Beak and coworkers showed that enantioselectivity is achieved through an asymmetric deprotonation to give an enantioenriched organolithium intermediate, which undergoes cyclization faster than epimerization. 

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... 

Asymmetric deprotonation with alkyllithinm-(—)-sparteine SnBn3... 

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... 

Many chiral bidentate ligands and their ability for supporting the asymmetric deprotonation of 149 have been investigated however, sparteine remained unbeaten. (—)-a-Isosparteine (14) does not support this deprotonation. 

The asymmetric lithiation/substitution of Af-Boc-Af-(3-chloropropyl)-2-alkenylamines 395 by w-BuLi/(—)-sparteine (11) provides (5 )-Af-Boc-2-(alken-l-yl)pyrrolidines 397 via the allyllithium-sparteine complexes 396 (equation 106) . Similarly, the piperidine corresponding to 397 was obtained from the Af-(4-chlorobutyl)amine. Intramolecular epoxide openings gave rise to enantioenriched pyrrolidinols. Beak and coworkers conclude from further experiments that an asymmetric deprotonation takes place, but it is followed by a rapid epimerization a kinetic resolution in favour of the observed stereoisomer concludes the cyclization step. 

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