四川大学冯小明团队报道了基于空间偏置硝基转移的铁催化硫化物不对称酰化反应。相关研究成果于2024年6月15日发表在国际顶尖学术期刊《美国化学会杂志》。

过渡金属催化的对映选择性硝基转移到硫化物，已成为快速构建对映富集亚磺酰胺的最有力策略之一。然而，与贵金属相比，实现对含地球丰富的高活性过渡金属类硝基中间体的立体控制，仍然是一个艰巨的挑战。

该文中，研究人员公开了一种使用亚氨基二胺作为硝基前体，手性铁（II）/N，N′-二氧化物催化的二烷基和烷基芳基硫化物的对映选择性酰亚胺化反应。以中等至良好的产率获得了一系列具有高对映选择性的手性亚磺酰亚胺（56个实例，高达99%的产率，98:2 e.r.）。该方法的实用性通过复杂分子的后期修饰，与手性杀虫剂磺基恶氟和相关生物活性化合物中间体的合成得到了证明。

通过实验研究和理论计算，确定了一种水键合的高自旋类硝基铁为关键中间体。观察到的立体选择性源于手性洞穴中配体的酰胺单元与硫化物的庞大取代基之间的空间排斥。此外，在铁（III）/N，N′-二氧化物络合物的存在下，二恶唑酮被证明是合适的酰基硝基前体，导致形成对映选择性反转的亚磺酰亚胺（14个实例，高达81%的产率，97:3 e.r.）。

附：英文原文

Title: Iron-Catalyzed Asymmetric Imidation of Sulfides via Sterically Biased Nitrene Transfer

Author: Zhenzhong Liu, Hongli Wu, Helong Zhang, Fang Wang, Xiaohua Liu, Shunxi Dong, Xin Hong, Xiaoming Feng

Issue&Volume: June 15, 2024

Abstract: Transition-metal-catalyzed enantioselective nitrene transfer to sulfides has emerged as one of the most powerful strategies for rapid construction of enantioenriched sulfimides. However, achieving stereocontrol over highly active earth-abundant transition-metal nitrenoid intermediates remains a formidable challenge compared with precious metals. Herein, we disclose a chiral iron(II)/N,N′-dioxide-catalyzed enantioselective imidation of dialkyl and alkyl aryl sulfides using iminoiodinanes as nitrene precursors. A series of chiral sulfimides were obtained in moderate-to-good yields with high enantioselectivities (56 examples, up to 99% yield, 98:2 e.r.). The utility of this methodology was demonstrated by late-stage modification of complex molecules and synthesis of the chiral insecticide sulfoxaflor and the intermediates of related bioactive compounds. Based on experimental studies and theoretical calculations, a water-bonded high-spin iron nitrenoid species was identified as the key intermediate. The observed stereoselectivity was original from the steric repulsion between the amide unit of the ligand in the chiral cave and the bulky substituent of sulfides. Additionally, dioxazolones proved to be suitable acylnitrene precursors in the presence of an iron(III)/N,N′-dioxide complex, resulting in the formation of enantioselectivity-reversed sulfimides (14 examples, up to 81% yield, 97:3 e.r.).

DOI: 10.1021/jacs.4c04855

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c04855