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