Enantioselective Synthesis of a Highly Potent Selective Serotonin Reuptake Inhibitor. An Application of Imidazolidinone Catalysis to the Alkylation of Indoles with an α,β-Disubstituted α,β-Unsaturated Aldehyde

The synthesis of the highly potent and selective serotonin reuptake inhibitor 1 (BMS-594726) is described. In the key construction step, an
enantioselective alkylation of the indole nucleus with an α-branched α,β-unsaturated aldehyde 7 was accomplished utilizing MacMillan's
imidazolidinone catalyst 3b. A rationale is presented for the unexpected stereochemical result, as well as the novel reactivity of the α-branched
substrate.