Phospha-Münchnones: Electronic Structures and 1,3-Dipolar Cycloadditions

Abstract

The reaction of imines, acid chlorides, PR(3), and base generates a new class of 1,3-dipoles: phospha-Munchnones. These 1,3-dipoles can undergo cycloadditions with alkynes followed by loss of phosphine oxides to form pyrroles. Cycloaddition reactivity is dependent upon the PR(3) employed, with PhP(catechyl) (catechyl = o-O(2)C(6)H(4)) providing the most rapid cycloadditions and optimal pyrrole yields. (1)H, (13)C, and (31)P NMR analysis and computations indicate that electron-poor catechyl-substituted phosphonites and phosphites favor a cyclic 1,3-dipolar structure, while more electron-rich phosphines instead favor the valence tautomeric acyclic ylides. X-ray crystallographic studies confirm this. Density functional theory calculations support the wide variety of P-O interactions induced by different PR(3) groups and indicate that the most efficient concerted 1,3-dipolar cycloadditions are those for dipoles whose ground-state geometry is most like the transition-state geometry. Reactions of these dipoles with monosubstituted alkynes bearing an electron-withdrawing group are calculated to occur by stepwise mechanisms. The presence of the phosphorus unit creates a large electronic bias across the 1,3-dipole, allowing for regioselective cycloadditions with substituted alkynes.