Easy access to 2-arylpyrrolidines

The most convergent and reliable method yet for constructing 2-arylpyrrolidines-a structural motif found in many biologically active compounds and chiral auxiliaries used in asymmetric catalysis-has been developed by process chemists at Merck Research Laboratories in Rahway, N.J (J. Am. Chem. Soc., published online March 1, dx.doi.org/10.1021/ja0605265). Kevin R. Campos and coworkers report a one-pot, enantioselective process that can be used to prepare a broad range of functionalized 2-aryl-N-Boc-pyrrolidines from N-Boc-pyrrolidine with high enantioselectivity (shown; Boc = tert-butoxycarbonyl, Ar = aryl). The methodology relies on the asymmetric deprotonation of N-Boc-pyrrolidine with sec-butyllithium and the chiral diamine (–)-sparteine, followed by transmetalation with zinc. The 2-pyrrolidinozinc reagent generated is then coupled to functionalized aryl halides at room temperature using a palladium catalyst. Preliminary unpublished results suggest that the arylation reaction will be applicable to other substrates as well, Campos notes.