The formation of enantiomerically enriched products from chiral organolithium species is a highly efficient and selective approach for organic synthesis. [1] The majority of examples involve the selective asymmetric deprotonation of a prochiral hydrogen atom adjacent to an oxygen or nitrogen atom, such as the method developed by the groups of Hoppe and Beak in which sec-butyllithium and (À)-sparteine is used as the chiral base. [2] However, an alternative mode of asymmetric induction exists, in which the chiral, racemic organolithium species is formed and complexed with a chiral ligand to promote asymmetric substitution. We report here the first highly enantioselective substitution of nonactivated organolithium species at ambient temperature.
Asymmetric substitution requires, for high yields, a dynamic resolution [3] in which the reacting chiral center can invert under the reaction conditions. Success has been achieved with lithiated allylic or benzylic substrates in the presence of a chiral ligand through either a dynamic thermodynamic or a dynamic kinetic resolution pathway. [4±7] Examples with a-thio and a-seleno organolithium species have also been reported, [8] however, to our knowledge there are no reports of dynamic resolution, followed by addition of an electrophile, of other nonactivated lithiated species. This may be a consequence of the common perception that organolithium species should be generated and treated at low temperature (typically À78 8C); under these conditions, although allylic, benzylic, a-thio and a-seleno organolithium species undergo racemization, [9] nonactivated chiral organolithium species do not normally racemize. For example, a-amino organolithium species display configurational stability at low temperature. [10] We have found, however, that the formation of a-amino organolithium species and their racemization is possible at room temperature. [11] We therefore set out to substitute racemic a-amino organolithium species asymmetrically in the presence of a chiral ligand.
Extending our work on intramolecular carbolithiation, [11, 12] we studied the dynamic resolution of chiral 2-lithiopyrrol-COMMUNICATIONS