Enantioselective synthesis of a highly potent selective serotonin reuptake inhibitor. An application of imidazolidinone catalysis to the alkylation of indoles with an alpha,beta-disubstituted alpha,beta-unsaturated aldehyde

H Dalton King; Zhaoxing Meng; Derek Denhart; Ronald Mattson; Roy Kimura; Dedong Wu; Qi Gao; John E Macor

doi:10.1021/ol051000c

Enantioselective synthesis of a highly potent selective serotonin reuptake inhibitor. An application of imidazolidinone catalysis to the alkylation of indoles with an alpha,beta-disubstituted alpha,beta-unsaturated aldehyde

Org Lett. 2005 Aug 4;7(16):3437-40. doi: 10.1021/ol051000c.

Authors

H Dalton King¹, Zhaoxing Meng, Derek Denhart, Ronald Mattson, Roy Kimura, Dedong Wu, Qi Gao, John E Macor

Affiliation

¹ Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA.

PMID: 16048311
DOI: 10.1021/ol051000c

Abstract

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 alpha-branched alpha,beta-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 alpha-branched substrate. [reaction: see text]

MeSH terms

Aldehydes / chemistry
Catalysis
Cyclopentanes / chemical synthesis*
Cyclopentanes / chemistry
Cyclopentanes / pharmacology*
Imidazoles / chemistry*
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology*
Selective Serotonin Reuptake Inhibitors / chemical synthesis*
Selective Serotonin Reuptake Inhibitors / chemistry
Selective Serotonin Reuptake Inhibitors / pharmacology*
Stereoisomerism

Substances

Aldehydes
BMS-594726
Cyclopentanes
Imidazoles
Indoles
Serotonin Uptake Inhibitors