Enantioselective Synthesis of Bicyclo[6.1.0]nonane-9-carboxylic Acids via Me2AlOTf-Promoted Intramolecular Friedel-Crafts Alkylation of Arenes with the γ-Lactone Moiety of 3-Oxabicyclo[3.1.0]hexan-2-ones

Abstract

A strategy to rapidly assemble enantiomerically pure bicyclo [6.1.0]nonane-9-carboxylic acids via Me2AlOTf-promoted intramolecular Friedel-Crafts alkylation of tethered π-nucleophiles with the γ-lactone moiety of 3-oxabicyclo-[3.1.0]hexan-2-ones is described. The approach begins with the enantioselective synthesis of 3-oxabicyclo[3.1.0]hexan-2-ones bearing a tethered π-nucleophile at the 6-position by intramolecular Rh(II)-catalyzed cyclopropanation of allylic diazoacetates, prepared from the corresponding (Z)-allylic alcohols. Me 2AlOTf-induced intramolecular Friedel-Crafts cyclization provides medium-sized carbocycles and heterocycles in high yields without requiring high-dilution or slow substrate addition techniques. The scope and limitations of this synthetic methodology are presented.