Stereospecific Cross-Coupling Reactions of Aryl-Substituted Tetrahydrofurans, Tetrahydropyrans, and Lactones

The
stereospecific ring-opening of O-heterocycles to provide acyclic
alcohols and carboxylic acids with controlled formation of a new C–C
bond is reported. These reactions provide new methods for synthesis
of acyclic polyketide analogs with complex stereochemical arrays.
Stereoselective synthesis of the cyclic template is utilized to control
relative configuration; subsequent stereospecific nickel-catalyzed
ring-opening affords the acyclic product. Aryl-substituted tetrahydrofurans
and tetrahydropyrans undergo nickel-catalyzed Kumada-type coupling
with a range of Grignard reagents to furnish acyclic alcohols with
high diastereoselectivity. Enantioenriched lactones undergo Negishi-type
cross-coupling with dimethylzinc to afford enantioenriched carboxylic
acids. Application in a two-step enantioselective synthesis of an
anti-dyslipidemia agent is demonstrated.