Assembly of Diverse 3-Methylenetetrahydrofurans via Palladium-Catalyzed Cascade Carboetherification of Buta-1,3-Dienes with Alkynols

TL;DR

This paper presents a new and efficient method for creating 3-methylenetetrahydrofuran compounds using a palladium-catalyzed reaction.

Contribution

The novel contribution is a palladium-catalyzed cascade carboetherification method for assembling diverse 3-methylenetetrahydrofurans.

Findings

The method shows excellent functional group compatibility and good regioselectivity.

A wide range of functional groups and aromatic heterocycles are tolerated, yielding products in moderate to good yields.

The approach is scalable and applicable for the synthesis of organic functional molecules.

Abstract

Tetrahydrofuran scaffolds have found promising applications in both pharmaceutical chemistry and organic synthesis but remain underexplored owing to the challenges associated with their preparation. Herein, we have developed a robust synthetic strategy for the palladium-catalyzed cascade annulation reaction of buta-1,3-dienes with alkynols for the assembly of diverse 3-methylenetetrahydrofurans with excellent functional group compatibility and good regioselectivity. More importantly, this protocol features broad substrate scope, good functional group tolerance, and good step- and atom-economy. A diverse array of functional groups such as halogen atoms, aldehyde, nitro, ester, and several aromatic heterocycles were also nicely tolerated and provided the corresponding products in moderate to good yields. It is noteworthy that the practicability is further verified by gram-scale experiments and synthetic transformation to access organic functional molecules.

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