Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, China.
University of Chinese Academy of Sciences, 100049, Beijing, China.
Nat Commun. 2023 Jul 8;14(1):4044. doi: 10.1038/s41467-023-39707-8.
Direct synthesis of ketones from aldehydes features high atom- and step-economy. Yet, the coupling of aldehydes with unactivated alkyl C(sp)-H remains challenging. Herein, we develop the synthesis of ketones from aldehydes via alkyl C(sp)-H functionalization under photoredox cooperative NHC/Pd catalysis. The two-component reaction of iodomethylsilyl alkyl ether with aldehydes gave a variety of β-, γ- and δ-silyloxylketones via 1,n-HAT (n = 5, 6, 7) of silylmethyl radicals to generate secondary or tertiary alkyl radicals and following coupling with ketyl radicals from aldehydes under photoredox NHC catalysis. The three-component reaction with the addition of styrenes gave the corresponding ε-hydroxylketones via the generation of benzylic radicals by the addition of alkyl radicals to styrenes and following coupling with ketyl radicals. This work demonstrates the generation of ketyl radical and alkyl radical under the photoredox cooperative NHC/Pd catalysis, and provides two and three component reactions for the synthesis of ketones from aldehydes with alkyl C(sp)-H functionalization. The synthetic potential of this protocol was also further illustrated by the late-stage functionalization of natural products.
醛与未活化的烷基 C(sp)-H 的偶联仍然具有挑战性。在此,我们通过光氧化还原协同 NHC/Pd 催化发展了醛通过烷基 C(sp)-H 官能化来合成酮。碘甲基硅烷基醚与醛的二组分反应通过硅甲基自由基的 1,n-HAT(n=5,6,7)生成仲或叔烷基自由基,并在光氧化还原 NHC 催化下与醛的酮基自由基偶联,生成各种β-、γ-和δ-硅氧代酮。通过添加苯乙烯的三组分反应,通过烷基自由基加成到苯乙烯中生成苄基自由基,并与醛的酮基自由基偶联,生成相应的ε-羟基酮。这项工作证明了在光氧化还原协同 NHC/Pd 催化下可以生成酮基自由基和烷基自由基,并提供了两种和三种组分反应,用于通过烷基 C(sp)-H 官能化从醛合成酮。该方案的合成潜力也通过天然产物的后期官能化进一步得到了说明。
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