Plachinski Ellie F, Qian Ruoyu Zoe, Villanueva Rodrigo, Poole Darren L, Rosenthal Tay, Yoon Tehshik P
Department of Chemistry, University of Wisconsin─Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
Molecular Modalities Capabilities, GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, U.K.
J Am Chem Soc. 2024 Nov 20;146(46):31400-31404. doi: 10.1021/jacs.4c13596. Epub 2024 Nov 7.
Bicyclo[2.1.1]hexanes have emerged as valuable scaffolds for the design of new pharmaceutical and agrochemical active ingredients. These structures can be efficiently synthesized via [2π + 2σ] photocycloadditions; however, control over the absolute stereochemistry of these strain-releasing reactions has remained challenging. Herein, we demonstrate that Brønsted acid catalyzed chromophore activation of -acyl imidazoles enables highly enantioselective [2π + 2σ] photocycloadditions. Because this approach is agnostic to the identity of the coupling partner, the same strategy can be used to synthesize several other medicinally relevant strained small-ring structures.
双环[2.1.1]己烷已成为设计新型药物和农用化学品活性成分的重要骨架。这些结构可以通过[2π + 2σ]光环加成反应高效合成；然而，控制这些应变释放反应的绝对立体化学仍然具有挑战性。在此，我们证明布朗斯特酸催化的酰基咪唑发色团活化能够实现高度对映选择性的[2π + 2σ]光环加成反应。由于这种方法与偶联伙伴的身份无关，因此可以使用相同的策略来合成其他几种与药物相关的应变小环结构。
