The development of transition-metal catalyzed enantioselective and diastereoselective transformations has contributed many advances in the field of synthetic organic chemistry. Particularly, stereoselective desymmetrization of prochiral cyclohexadienones represents a powerful strategy for accessing highly functionalized and stereochemically enriched scaffolds, which are often found in biologically active compounds and natural products. In recent years, several research groups including our group have made a significant progress on transition-metal catalyzed stereoselective desymmetrizations of 2,5-cyclohexadienones. In this account, we will provide an overview of the recent developments in this area employing Pd, Cu, Rh, Au, Ag, Ni, Co, and Mn-catalysts.

An unconventional Ag­(I)-catalyzed intramolecular cyclopropanation of prochiral alkyne-tethered cyclohexadienones has been developed using simple perchloric acid as an external oxidant. The transformation involves the formation of a perchloryloxy vinyl-silver species, which then proceeds through either intramolecular conjugate addition or an α-oxo silver carbene pathway to yield cyclopropane fused tricyclic enones with high diastereoselectivity. In the case of C-tethered cyclohexadienones, the reaction proceeds further via acid mediated semipinacol-type rearrangement to give complex and highly strained tricyclo­[3.3.1.0]­nonanediones. This cascade annulation has wide functional-group tolerance and broad substrate scope. Late-stage functionalization of estrone was also demonstrated with excellent diastereoselectivity.

Herein we report a highly regioselective silver­(I)-catalyzed intramolecular annulation of alkyne-tethered cyclohexadienones to access meta-substituted phenols with enone functionality, which are difficult to synthesize from conventional methods. The reaction proceeds via intramolecular 1,6-enyne cyclization followed by aromatization and subsequent oxetene ring rearrangement. This strategy has also been compatible with a wide range of C-tethered cyclohexadienones to afford indanes in high yields. The unique functionality of products allows further transformations to expand the diversity.