Enantio-and diastereoselective desymmetrization of α-alkyl-α-diazoesters by dirhodium(II)-catalyzed intramolecular C-H insertion

The first enantio-and diastereoselective construction of fused bicyclic ring systems via intramolecular C-H insertion reaction of sigma-symmetric alpha-alkyl-alpha-diazoesters is described. With dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh-2(S-PITL)(4), the C-H insertion proceeded in a chemoselective manner to give methyl bicyclo[3.3.0]oct-7-ene-2-carboxylate and methyl bicyclo[4.3.01nonane-7-carboxylate derivatives with up to 99% ee and perfect cis diastereoselectivity. The utility of this protocol was demonstrated by the catalytic asymmetric synthesis of a key intermediate in Whitesell's synthesis of udoteatrial hydrate. (C) 2016 Elsevier Ltd. All rights reserved.