Catalyst-Controlled Divergent Synthesis of Bicyclo[2.1.1]hexanes and Cyclobutenes: The Unique Effect of Au(I)

催化剂控制的双环[2.1.1]己烷和环丁烯的发散合成:Au(I)的独特作用

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Abstract

Catalyst-controlled chemodivergent synthesis is a powerful strategy for exploring the chemical space. We report a Cu-(I)/Au-(I)-catalyzed chemodivergent reaction of bicyclo[1.1.0]-butane amides with azadienes, enabling access to two valuable product classes: bicyclo[2.1.1]-hexanes and cyclobutenes. Cu-(I) catalysis promotes a highly efficient formal cycloaddition to furnish bicyclo[2.1.1]-hexanes, whereas Au-(I) uniquely facilitates an addition-elimination pathway, selectively yielding cyclobutenes. Both transformations exhibit excellent chemoselectivity, high efficiency, and a broad substrate scope. The multifunctionalized products are readily scalable to gram quantities and undergo diverse downstream modifications including spirocyclization. DFT calculations provide mechanistic insight into divergent reactivity. Cu-(I) favors a linear two-coordinate geometry in the transition state, accelerating the intramolecular cyclization. In contrast, Au-(I) stabilizes key intermediates via a four-coordinate geometry, enabling intramolecular proton transfer and reversing the inherent chemoselectivity. This work highlights Au-(I)'s unique property as a useful tool for controlling reaction pathways and expanding chemical space through molecular diversification.

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