Lateral lithiation stereoselectivity

The directing effect of the amide group can then be used a second time in the lateral lithiation of 503 to give an organolithium 507 which adds to the imine 508 in a stereoselective manner, probably under thermodynamic control (imine additions of laterally lithiated amides appear to be reversible). Warming the reaction mixture to room temperature leads to a mixture of 509 and some of the (ultimately required) cyclized product... 

Sulphoxides direct lateral lithiation in a reaction which is also highly stereoselective. In common with other electrophiles, ClC02Et produces as a single diastereoisomer of 544... 

Most benzylic organolithiums, unless they bear an a heteroatom, are configurationally unstable over a period of seconds or more" , so any stereoselectivity in lateral lithiation is rarely detectable. However, as implied above, the lateral lithiation of tertiary 1-naphthamides 570 is stereoselective, and yields a single diastereoisomeric atropiso-mer of the organolithium 571 Both diastereoisomers of 571 were characterized by... 

Enantioselective reactions of laterally lithiated amides and anilides have been reported by Beak and coworkers but these are properly asymmetric transformations in which stereoselectivity arises subsequent to the lateral lithiation step they are not enantioselective lithiations. 

Sulfoxides direct lateral lithiation in a reaction which is also highly stereoselective.409 In common with other electrophiles, ClC02Et produces as a single diastereoisomer of 455 from 454, and Raney nickel can be used to remove the sulfinyl group from the product, making this a very versatile method for asymmetric functionalisation of a benzyl group. 

Treatment of the laterally lithiated amide generated from lactam 273 with LDA with /ra r-2-phenylsulfonyl-3-phenyloxaziridine 33 afforded hydroxyl product 274 in 85% yield as a single isomer <1999JOC8627>. Use of (+)-(camphorsulfonyl)oxaziridine 202 gave similar results. The /ra t-stereoselectivity is consistent with the earlier finding that the hydroxylation stereochemistry is controlled by nonbonded steric interactions in the transition state such that the oxygen of the oxaziridine is delivered from the sterically least hindered direction. Treatment of 275 with LDA followed by (+)-(camphorsulfonyl)oxaziridine 202 afforded hydroxyl product 276 in 47% yield and 60% ee <1997T8881>. 

Benzylic organolithium compounds are in general configurationally unstable. However, the lateral lithiation of tertiary 2-alkyl-l-naphthamides, such as 170, was stereoselective and yielded a single diastereomeric atropisomer 171 [143], which reacted with several electrophiles with retention, to give compounds 172 [144], except with trialkyltin halides for which an inversion of the configuration was observed (Scheme 2.23) [144a[. 

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