Hervieu Cédric, Kirillova Mariia S, Suárez Tatiana, Müller Marco, Merino Estíbaliz, Nevado Cristina
Department of Chemistry, University of Zurich, Zurich, Switzerland.
Department of Organic and Inorganic Chemistry, Chemical Research Institute Andrés M. del Río (IQAR), University of Alcala, Madrid, Spain.
Nat Chem. 2021 Apr;13(4):327-334. doi: 10.1038/s41557-021-00668-4. Epub 2021 Apr 8.
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.
在非环状体系中构建全碳季碳中心的不对称结构，长期以来一直是合成化学家面临的挑战。除了极性和自由基方法外，重排反应是一个有吸引力的平台，但仍迫切需要广泛适用的方法。在此，我们报道了一种不对称的、自由基亚磺酰基-斯迈尔斯重排反应，用于合成带有α-全碳季碳中心的非环状酰胺。我们的策略使用对映体富集的N-芳基亚磺酰基丙烯酰胺作为受体，以接受在温和光氧化还原条件下原位产生的各种自由基。亚磺酰胺基团不仅引导芳基部分向酰胺的α-碳进行1,4-迁移，从而决定其绝对构型，还作为无痕手性助剂发挥作用。通过这个多组分过程得到的酰胺在药物、农用化学品和生物活性天然产物中普遍存在，并且可以转化为有价值的手性α,α-二取代酸、羟吲哚以及β,β-二取代胺，突出了这种转化的合成潜力。
