Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

Abstract

Asymmetric allylic alkylation is a powerful reaction that allows the enantioselective formation of C–C bonds. Here we describe the asymmetric alkylation of alkylzirconium species to racemic 3,6-dihydro-2H-pyrans. Two systems were examined: 3-chloro-3,6-dihydro-2H-pyran using linear optimization (45–93% ee, up to 33% yield, 5 examples) and 3,6-dihydro-2H-pyran-3-yl diethyl phosphate with the assistance of a design of experiments statistical approach (83% ee, 12% yield). 1H NMR spectroscopy was used to gain insight into the reaction mechanisms.

Keywords

• allylic alkylation
• asymmetric catalysis
• copper
• design of experiments
• dynamic kinetic asymmetric transformation
• heterocycles
• Schwartz reagent