Hydroxy alkenenitriles: diastereoselective conjugate addition-alkylations.
Chelation-controlled conjugate addition of Grignard reagents to cyclic and acyclic gamma-hydroxyalkenenitriles stereoselectively generates beta-substituted hydroxynitriles. t-BuMgCl-induced deprotonation of gamma-hydroxyalkenenitriles followed by chloride-alkyl exchange from a second Grignard reagent, generates an alkylmagnesium alkoxide that triggers conjugate addition. Alkylation of the resulting magnesiated nitrile with alkyl halide and carbonyl electrophiles efficiently installs two new bonds and up to three stereocenters in a single synthetic operation.
Fleming
Fraser F
FF
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282-1530, USA. flemingf@duq.edu
Wang
Qunzhao
Q
Steward
Omar W
OW
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D000478:Alkylation; D002384:Catalysis; D002614:Chelating Agents / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D006900:Hydroxylation; D007202:Indicators and Reagents; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000475:Alkenes; D002614:Chelating Agents; D007202:Indicators and Reagents; D009570:Nitriles