Double Strain-Release [2π+2σ]-Photocycloaddition

作者：Subhabrata Dutta, Yilin Lu, Johannes E. Erchinger, Huiling Shao, Emanuel Studer, Felix Schäfer, Huamin Wang, Debanjan Rana, Constantin G. Daniliuc, K. N. Houk, Frank Glorius · 发表于：Journal of the American Chemical Society · 年份：2024 · DOI：10.1021/jacs.3c11563 · 被引用次数：112 · 研究领域：Organic Chemistry Cycloaddition Reactions、Chemistry and Chemical Engineering、Radical Photochemical Reactions

In pursuit of potent pharmaceutical candidates and to further improve their chemical traits, small ring systems can serve as a potential starting point. Small ring units have the additional merit of loaded strain at their core, making them suitable reactants as they can capitalize on this intrinsic driving force. With the introduction of cyclobutenone as a strained precursor to ketene, the photocycloaddition with another strained unit, bicyclo[1.1.0]butane (BCB), enables the reactivity of both π-units in the transient ketene. This double strain-release driven [2π+2σ]-photocycloaddition promotes the synthesis of diverse heterobicyclo[2.1.1]hexane units, a pharmaceutically relevant bioisostere. The effective reactivity under catalyst-free conditions with a high functional group tolerance defines its synthetic utility. Experimental mechanistic studies and density functional theory (DFT) calculations suggest that the [2π+2σ]-photocycloaddition takes place via a triplet mechanism.