Abstract
Cyclopropanes represent a class of versatile building blocks in modern organic synthesis. While the release of ring strain offers a thermodynamic driving force, the control of selectivity for C–C bond cleavage and the subsequent regiochemistry of the functionalization remains difficult, especially for unactivated cyclopropanes. Here we report a photoredox-coupled ring-opening oxo-amination of electronically unbiased cyclopropanes, which enables the expedient construction of a host of structurally diverse β-amino ketone derivatives. Through one electron oxidation, the relatively inert aryl cyclopropanes are readily converted into reactive radical cation intermediates, which in turn participate in the ensuing ring-opening functionalizations. Based on mechanistic studies, the present oxo-amination is proposed to proceed through an SN2-like nucleophilic attack/ring-opening manifold. This protocol features wide substrate scope, mild reaction conditions, and use of dioxygen as an oxidant both for catalyst regeneration and oxygen-incorporation. Moreover, a one-pot formal aminoacylation of olefins is described through a sequential cyclopropanation/oxo-amination.
Highlights
Cyclopropanes represent a class of versatile building blocks in modern organic synthesis
In 2014, Nicewicz and co-workers reported seminal work on intermolecular anti-Markovnikov hydroamination of alkenes by photoredox catalysis, wherein an alkene radical cation intermediate is generated upon single electron oxidation and undergoes nucleophilic addition by amine derivatives (Fig. 1b)[27]
Notable features of this approach include: (1) aryl cyclopropanes are readily oxidized via Single electron transfer (SET) to aryl radical cations, which activate the otherwise relatively inert neighboring cyclopropane motif; (2) dioxygen has a dual role in this transformation: it acts as an oxidant for catalyst regeneration and serves to oxygenate the benzylic radical intermediate; (3) the products are β-azaaryl ketones, which are core structural motifs in naturally occurring molecules and represent key building blocks in organic synthesis[64,65]; and (4) a one-pot formal aminoacylation of simple alkenes is accomplished through a cascade cyclopropanation/oxo-amination (Fig. 1d)[66,67]
Summary
Cyclopropanes represent a class of versatile building blocks in modern organic synthesis. With our continuing interest in developing original synthetic transformations using photoredox catalysis, we present the example of a photocatalytic ring-opening 1,3-oxo-amination of unactivated cyclopropanes using molecular oxygen and azaarene nucleophiles (Fig. 1c)[28,62,63].
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