Phosphine-Catalyzed [4+2] Annulations of 2-Alkylallenoates and Olefins: Synthesis of Multisubstituted Cyclohexenes

From our investigations on phosphine-catalyzed [4+2] annulations between alpha-alkyl allenoates and activated olefins for the synthesis of cyclohexenes, we discovered a hexamethylphosphorous triamide (HMPT)-catalyzed [4+2] reaction between alpha-alkyl allenoates 1 and arylidene malonates or arylidene cyanoacetates 2 that provides highly functionalized cyclohexenes 3 and 4 in synthetically useful yields (30-89%), with moderate to exclusive regioselectivity, and reasonable diastereoselectivity. Interestingly, the [4+2] annulations between the alpha-alkyl allenoates 1 and the olefins 2 manifested a polarity inversion of the 1,4-dipole synthon 1, depending on the structure of the olefin, thus providing cyclohexenes 3 exclusively when using arylidene cyanoacetates. The polarity inversion of alpha-alkyl allenoates from a 1,4-dipole A to B under phosphine catalysis can be explained by an equilibrium between the phosphonium dienolate C and the phosphorous ylide D.