Intermolecular Oxidative Radical Addition to Aromatic Aldehydes: Direct Access to 1,4- and 1,5-Diketones via Silver-Catalyzed Ring-Opening Acylation of Cyclopropanols and Cyclobutanols

Abstract

A novel silver-catalyzed ring-opening acylation of cyclopropanols and cyclobutanols is described. The reaction proceeds under mild and neutral conditions and provides a facile access to nonsymmetric 1,4- and 1,5-diketones in promising yields with broad substrate scope. Mechanistic studies including DFT calculations suggest the involvement of an uncommon water-assisted 1,2-HAT process, which is strongly exothermic and thus promotes addition of carbon radicals to aldehydes. In contrast to traditional reductive radical addition protocols, this work represents the first example of the intermolecular oxidative radical addition to aldehydes, thus offering a novel strategy for the direct synthesis of acyclic ketones from readily accessible aldehydes.

Aldehydes: magnificent acyl equivalents for direct acylation

“…Che et al in 2018, described Ag-catalyzed ring opening acylation of cyclopropanols and cyclobutanols through intermolecular oxidative radical addition of aromatic aldehydes using mild and neutral reaction conditions. 65 1-(4-Methoxyphenyl)cyclobutan-1-ol and p-cynobenzaldehydye were chosen as model reaction substrates to evaluate the reaction parameters. Using the optimized reaction conditions, the substrate scope with respect to cyclopropanols, cyclobutanols and aromatic aldehydes was explored and 32 derivatives were prepared in 36-92% yield at 50 o C (Scheme 30A).…”

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

“…In 2018, Zhu and co-workers also reported the first silver-catalyzed ring-opening and acylation of cyclopropanols 91 with aldehydes 48 for the synthesis of 1,4-diketones 144 (Scheme 39) [119]. They proposed that the involvement of an uncommon water-assisted 1,2-HAT process was strongly exothermic and it promoted the addition of alkyl radicals to C=O bonds in aldehydes.…”

Visible-Light-Induced Alkoxyl Radicals Enable α-C(sp3)-H Bond Allylation

“…In contrast, the intramolecular C-H abstraction at positions other than δ-position by alkoxyl radicals has been less reported owing to the unfavorable transition states and high activation energies (Čeković, 2003, Čeković, 2005, Hartung, 2001, Chiba and Chen, 2014). Currently, there are only a few reports on the 1,2-HAT reactivity of alkoxyl radicals in theoretical or biological studies, and the synthetic utilization of 1,2-HAT for new C-C bond formation remains elusive (Buszek et al., 2011, Elford and Roberts, 1996, Fernández-Ramos and Zgierski, 2002, Konya et al., 2000, Gilbert et al., 1976, Che et al., 2016, Che et al., 2018). Here we report the first visible-light-induced α-C(sp 3 )-H allylation reaction enabled by the selective 1,2-HAT of alkoxyl radicals, which is facilitated by protic solvents and applicable to various α-carbonyl, α-cyano, α-trifluoromethyl, and benzylic C(sp 3 )-H bonds (Scheme 1B).

Scheme 1Selective C(sp 3 )-H Functionalization via Hydrogen Atom Transfer of Alkoxyl Radicalsphth, Phthalimide.

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