美国普林斯顿大学Robert R. Knowles教授带领的研究小组提出了可见光三重态光敏化促进的分子间交叉[2 + 2]环加成，并将其用于多取代2-氧杂螺[3.3]庚烷的快速合成中。该研究于2021年3月5日发表于国际一流学术期刊《美国化学会志》上。

在该文中，研究人员描述了一种环外亚芳基氧杂环丁烷、氮杂环丁烷、环丁烷与简单缺电子烯烃的分子间交叉选择性[2+2]光环加成反应。该反应发生在温和的条件下，在蓝光照射下使用商品化的Ir(III)光敏剂即可发生。该反应可以生成一系列多取代的2-氧杂螺[3.3]庚烷、2-氮杂螺[3.3]庚烷和螺[3.3]庚烷模块，这些模块作为偕二甲基和羰基的生物等效性基团，在药物化学中具有重要的意义。

在进一步研究中，研究人员将初步的环加成产物进一步转化，以证明这些产物的灵活性，即可以通过动力学或热力学的差向异构化选择性地获得syn-或anti-构象的非对映异构体。机理实验和密度泛函计算表明，该反应通过敏化的能量传递途径进行。

附：英文原文

Title: Intermolecular Crossed [2 + 2] Cycloaddition Promoted by Visible-Light Triplet Photosensitization: Expedient Access to Polysubstituted 2-Oxaspiro[3.3]heptanes

Author: Philip R. D. Murray, Willem M. M. Bussink, Geraint H. M. Davies, Farid W. van der Mei, Alyssa H. Antropow, Jacob T. Edwards, Laura Akullian D’Agostino, J. Michael Ellis, Lawrence G. Hamann, Fedor Romanov-Michailidis, Robert R. Knowles

Issue&Volume: March 5, 2021

Abstract: This paper describes an intermolecular cross-selective [2 + 2] photocycloaddition reaction of exocyclic arylidene oxetanes, azetidines, and cyclobutanes with simple electron-deficient alkenes. The reaction takes place under mild conditions using a commercially available Ir(III) photosensitizer upon blue light irradiation. This transformation provides access to a range of polysubstituted 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, and spiro[3.3]heptane motifs, which are of prime interest in medicinal chemistry as gem-dimethyl and carbonyl bioisosteres. A variety of further transformations of the initial cycloadducts are demonstrated to highlight the versatility of the products and enable selective access to either of a syn- or an anti-diastereoisomer through kinetic or thermodynamic epimerization, respectively. Mechanistic experiments and DFT calculations suggest that this reaction proceeds through a sensitized energy transfer pathway.

DOI: 10.1021/jacs.1c01173

Source: https://pubs.acs.org/doi/10.1021/jacs.1c01173