Enantioselective synthesis of bicyclo[6.1.0]nonane-9-carboxylic acids via Me2AlOTf-promoted intramolecular Friedel-Crafts alkylation of arenes with the gamma-lactone moiety of 3-oxabicyclo[3.1.0]hexan-2-ones

A strategy to rapidly assemble enantiomerically pure bicyclo6.1.0]nonane-9-carboxylic acids via Me2AlOTf-promoted intramolecular Friedel-Crafts alkylation of tethered pi-nucleophiles with the gamma-lactone moiety of 3-oxabicyclo3.1.0]hexan-2-ones is described. The approach begins with the enantioselective synthesis of 3-oxabicyclo3.1.0]hexan-2-ones bearing a tethered pi-nucleophile at the 6-position by intramolecular Rh(II)-catalyzed cyclopropanation of allylic diazoacetates, prepared from the corresponding (Z)-allylic alcohols. Me2AlOTf-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.