Journal of Organic Chemistry 2005-10-14

Stereoselective formation of carbon-carbon bonds via SN2-displacement: synthesis of substituted cycloalkyl[b]indoles.

Michael C Hillier, Jean-François Marcoux, Dalian Zhao, Edward J J Grabowski, Arlene E McKeown, Richard D Tillyer

Index: J. Org. Chem. 70(21) , 8385-94, (2005)

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Abstract

A general asymmetric synthesis of substituted cycloalkyl[b]indoles has been accomplished. The key features of this approach are (1) the utilization of a Japp-Klingemann condensation/Fischer cyclization to prepare cycloalkyl[b]indolones, (2) the asymmetric borane reduction of these heterocyclic ketones with (S)-OAB to obtain enantiomerically pure alcohols, and (3) the stereoselective S(N)2-displacement of these indole alcohol substrates with a carbon nucleophile under Mitsunobu conditions to set the C1 or C3 tertiary carbon stereocenter. The use of trimethylphosphine (PMe3) and bis(2,2,2-trichloroethyl) azodicarboxylate (TCEAD) was found to have an effect on the Mitsunobu dehydrative alkylation.