Gold(I)-Catalyzed Formal [2+2+2] Cycloaddition of Activated Alkynes and Carbonyls: One-Pot Synthesis of 2H-Pyrans

Abstract

The 2H-pyran is the structural motif embedded in many natural products and usually employed as a key intermediate in the synthesis of natural products and pharmaceutical molecules. While methods for the synthesis of dihydropyrans and tetrahydropyrans have been extensively explored, synthesis of stable 2H-pyrans remains an elusive challenge in current organic synthesis. This is because of the intrinsic instability of 2H-pyrans caused by an equilibrium with 1-oxatrienes via the electrocyclic ring-opening reactions. In this presentation, we describe an efficient one-pot synthesis of highly substituted 2H-pyrans using gold(I) pre-catalyst in combination with a metal triflate as a n activator and another metal triflate as an accelerator. Reactions of linear, cyclic ketones, and aldehydes with various activated alkynes under the above condition provided the corresponding 2H-pyrans in excellent regioselectivity. The newly developed synthetic method constitutes one of the first reports of gold(I)-catalyzed formal [2+2+2] cycloaddition between one unit of a carbonyl compound and two units of an activated alkyne. This method provides a straightforward and general access to various highly substituted 2H-pyrans by applying a combination of a carbonyl compound and an activated alkyne under a mild reaction condition.