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-ZUSCHRIFTEN 4043 detected by ESMS analysis of this mixture. Deprotonation of 1 with nbutyllithium/TMEDA at À78 8C followed by trapping with Ph 2 PCl at À30 8C provided the product of ortho lithiation±trapping in low yield.[15] Crystal structure analysis of 7: Bruker CCD platform diffractomer, 168(2) K, Mo Ka radiation, l ¼ 0.71073 ä, the structure was solved by direct methods (SHELXTL; G. M. Sheldrick, SHELXTL Version 5.10, Bruker Analytical X-Ray Systems, Inc.; Madison, WI, 1999); full-matrix least-squares refinement on F 2 (SHELXTL), structure presentation: crystal dimensions 0.22 î 0.18 î 0.08 mm 3 , orange crystals, space group P2 1 2 1 2 1 , orthorhombic, a ¼ 10.0557 (5) ä, b ¼ 17.7209(8) ä, c ¼ 19.4695(9) ä, V ¼ 3469.4(3) ä 3 , Z ¼ 4, 1 calcd ¼ 1.481 Mg m À3 , 2q max ¼ 56.588, 42 399 measured, 8460 independent reflections, R ¼ 0.0343, wR ¼ 0.0667, residual electron density ¼ 0.652 e ä À3...
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