瑞士苏黎世大学Cristina Nevado团队开发了不对称、可见光介导的自由基亚磺酰基Smiles重排获得全碳四元立体中心的策略。 相关研究成果于2021年4月8日发表在《自然-化学》。

在非循环环境中，所有碳四元中心的不对称结构对合成化学家来说是一个长期的挑战。除了极性方法和自由基方法外，重排反应是一个很有吸引力的平台，但对广泛应用的方法仍然需求很大。

该文中，研究人员报道了一个不对称的，自由基亚磺酰基Smiles重排，以获得带有α-全碳四元中心的无环酰胺的方法。其策略是使用对映体富集的N-芳基亚磺酰基丙烯酰胺作为受体，在温和的光氧化条件下原位产生各种自由基。磺胺基不仅引导芳基部分1,4-迁移到酰胺的α-碳上，从而控制其绝对构型，而且还起到无痕手性助剂的作用。

该多组分方法得到的酰胺广泛应用于医药、农药和生物活性天然产物中，可以转化为有价值的手性α，α-二取代酸、羟肟醇以及β，β-二取代胺，突出了这种转化的合成潜力。

附：英文原文

Title: Asymmetric, visible light-mediated radical sulfinyl-Smiles rearrangement to access all-carbon quaternary stereocentres

Author: Cdric Hervieu, Mariia S. Kirillova, Tatiana Surez, Marco Mller, Estbaliz Merino, Cristina Nevado

Issue&Volume: 2021-04-08

Abstract: The asymmetric construction of all-carbon quaternary centres within acyclic settings represents a long-standing challenge for synthetic chemists. Alongside polar and radical methods, rearrangement reactions represent an attractive platform, but still broadly applicable methods are in high demand. Here we report an asymmetric, radical sulfinyl-Smiles rearrangement to access acyclic amides that bear an α-all-carbon quaternary centre. Our strategy uses enantioenriched N-arylsulfinyl acrylamides as acceptors for a variety of radicals produced in situ under mild photoredox conditions. The sulfinamido group not only directs the 1,4-migration of the aryl moiety onto the α-carbon of the amide, which thus governs its absolute configuration, but also functions as a traceless chiral auxiliary. The amides obtained in this multicomponent process are prevalent in pharmaceuticals, agrochemicals and bioactive natural products, and can be transformed into valuable chiral α,α-disubstituted acids, oxindoles as well as into β,β-disubstituted amines, highlighting the synthetic potential of this transformation.

DOI: 10.1038/s41557-021-00668-4

Source: https://www.nature.com/articles/s41557-021-00668-4