Collect. Czech. Chem. Commun. 2003, 68, 885-898

Diastereoselective Addition of α-Metalated Sulfoxides to Imines Revisited: Mechanism, Computational Studies, and the Effect of External Chiral Ligands

Brian Pedersen, Tobias Rein, Inger Søtofte, Per-Ola Norrby* and David Tanner*

Department of Chemistry, Technical University of Denmark, Buildings 201 and 207, Kemitorvet, DK-2800 Kgs. Lyngby, Denmark


Some new results on asymmetric synthesis via the addition of α-metalated methyl tolyl sulfoxides to imines are presented. Good diastereoselectivity (up to >98% d.e. for product 3g) can be obtained under conditions of kinetic control (short reaction time, low temperature). The transition state (a six-membered "flat chair") was probed by quantum mechanical calculations, which underpinned the idea of using external chiral ligands to enhance the diastereoselectivity of otherwise moderately selective reactions. In this way, the diastereomeric ratio of the product 3a could be raised from (84:16) to (>99:1) by use of a readily available C2-symmetric bis(sulfonamide) ligand.

Keywords: Diastereoselectivity; Chiral sulfoxides; Imines; N ligands; Quantum mechanical calculations; Asymmetric additions; Carbanions; Organolithium reagents.

References: 30 live references.