The conformational bias of aryl, arylsulfonyl geminally substituted tertiary carbon centers: applications in substrate-based stereocontrol.
Intramolecular nitrile oxide-olefin cycloaddition to form hexahydrobenzisoxazole 14, which engenders a phenylsulfonyl, 2,5-difluorophenyl geminally substituted carbon substructure, proceeds with up to 99% ds. A rationalization of the high level of substrate-based stereo-induction observed in this and related ketone and acrylonitrile metallohydride reductions, supported by single crystal X-ray crystallography, is presented.
Scott
Jeremy P
JP
Department of Process Research, Merck Sharp & Dohme Research Laboratories, Hoddesdon, Hertfordshire, UK. jeremy_scott@merck.com
Mullens
Peter R
PR
Brewer
Sarah E
SE
Brands
Karel M J
KM
Chilenski
Jennifer R
JR
Davies
Antony J
AJ
Gibb
Andrew D
AD
Lieberman
David R
DR
Oliver
Steven F
SF
Dolling
Ulf-H
UH
D000475:Alkenes / Q000737:chemistry; D018360:Crystallography, X-Ray; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D008968:Molecular Conformation; D013450:Sulfones / Q000737:chemistry
D000475:Alkenes; D006841:Hydrocarbons, Aromatic; D013450:Sulfones