title: Catalytic enantioselective cyclization/cross-coupling with alkyl electrophiles.
abstract: As part of our ongoing effort to expand the scope of cross-coupling reactions of alkyl electrophiles, we have pursued a strategy wherein the nucleophilic coupling partner includes a pendant olefin; after transmetalation by such a substrate, if β-migratory insertion proceeds faster than direct cross-coupling, an additional carbon-carbon bond and stereocenter can be formed. With the aid of a nickel/diamine catalyst (both components are commercially available), we have established the viability of this approach for the catalytic asymmetric synthesis of 2,3-dihydrobenzofurans and indanes. Furthermore, we have applied this new method to the construction of the dihydrobenzofuran core of fasiglifam, as well as to a cross-coupling with a racemic alkyl electrophile; in the latter process, the chiral catalyst controls two stereocenters, one that is newly generated in a β-migratory insertion and one that begins as a mixture of enantiomers.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Huan
authors.initials: H
authors.lastname: Cong
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Fu
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry; D009532:Nickel / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D001572:Benzofurans; D007189:Indans; D009532:Nickel; C043168:coumaran