Studies on regioselective addition of benzylic organometallics to α-oxoketene dithioacetals in our aromatic annelation protocol

Abstract

The α-oxoketenedithioacetals derived from various acyclic and cyclic active methylene ketones are shown to undergo either 1,2- or sequential 1,4- and 1,2-addition with various substituted benzylic Grignard reagents (or benzyl lithium) and 1-/2-(naphthylmethyl) Grignard reagents to give carbinol adducts which on facile BF₃.Et₂O induced cycloaromatization afford a variety of substituted naphthalenes, phenanthrenes and other condensed aromatics. This methodology has emerged as a versatile tool for the regioselective construction of aromatic ring via [3+3] annulation from readily available acyclic precursors. The various substituted benzylic Grignard reagents (or benzyl lithium) and the corresponding 1- and 2-(naphthylmethyl) reagents display diverse regioselectivity in these reactions via either 1,2-addition or sequential 1,4- and 1,2-addition depending on the substituents in the benzylic moiety, nature of the metal and the substrate oxoketenedithioacetals. The benzylic organocopper reagents undergo regioselective conjugate addition-displacement to give β-benzyl-β-methylthiomethylene ketones while the corresponding alkoxy substituted benzyl organocopper reagents gave unexpected results under these conditions. An attempt has been made to generalize some of these observations in terms of charge control 1,2- and orbital control 1,4-addition, although theoretical studies are needed to throw further light for better understanding of these results.