title: Stereoselective formation of carbon-carbon bonds via SN2-displacement: synthesis of substituted cycloalkyl[b]indoles.
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.
authors.affiliation: Department of Process Research, Merck and Company, P.O. Box 2000, Rahway, New Jersey 07065, USA. michael_hillier@merck.com
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hillier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Marcoux
authors.forename: Dalian
authors.initials: D
authors.lastname: Zhao
authors.forename: Edward J J
authors.initials: EJ
authors.lastname: Grabowski
authors.forename: Arlene E
authors.initials: AE
authors.lastname: McKeown
authors.forename: Richard D
authors.initials: RD
authors.lastname: Tillyer
mesh_terms: D002244:Carbon / Q000737:chemistry*; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D007211:Indoles; D002244:Carbon