Yang Shiyi, Yu Xiang, Szostak Michal
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States.
ACS Catal. 2023 Feb 3;13(3):1848-1855. doi: 10.1021/acscatal.2c05550. Epub 2023 Jan 17.
Transition-metal-catalyzed cross-coupling reactions of thioesters by selective acyl C(O)-S cleavage have emerged as a powerful platform for the preparation of complex molecules. Herein, we report divergent Liebeskind-Srogl cross-coupling of thioesters by Pd-NHC (NHC = N-heterocyclic carbene) catalysis. The reaction provides straightforward access to functionalized ketones by highly selective C(acyl)-S cleavage under mild conditions. Most crucially, the conditions enable direct functionalization of a range of complex pharmaceuticals decorated with a palette of sensitive functional groups, providing attractive products for medicinal chemistry programs. Furthermore, decarbonylative Liebeskind-Srogl cross-coupling by C(acyl)-S/C(aryl)-C(O) cleavage is reported. Cu metal cofactor directs the reaction pathway to acyl or decarbonylative pathway. This reactivity is applicable to complex pharmaceuticals. The reaction represents the mildest decarbonylative Suzuki cross-coupling discovered to date. The Cu-directed divergent acyl and decarbonylative cross-coupling of thioesters opens up chemical space in complex molecule synthesis.
通过选择性酰基 C(O)-S 裂解实现的过渡金属催化硫酯交叉偶联反应，已成为制备复杂分子的强大平台。在此，我们报道了通过 Pd-NHC（NHC = N-杂环卡宾）催化实现硫酯的发散性 Liebeskind-Srogl 交叉偶联反应。该反应在温和条件下通过高度选择性的 C(酰基)-S 裂解，直接得到功能化的酮。最关键的是，这些条件能够使一系列带有多种敏感官能团的复杂药物直接功能化，为药物化学项目提供了有吸引力的产物。此外，还报道了通过 C(酰基)-S/C(芳基)-C(O) 裂解实现的脱羰 Liebeskind-Srogl 交叉偶联反应。铜金属辅因子引导反应途径走向酰基或脱羰途径。这种反应性适用于复杂药物。该反应是迄今为止发现的最温和的脱羰铃木交叉偶联反应。铜引导的硫酯发散性酰基和脱羰交叉偶联反应在复杂分子合成中开辟了化学空间。
