Photoinduced C—C Bond Cleavage and Oxidation of Cycloketoxime Esters

Abstract

A novel structural reorganization of cycloketoxime esters beyond the traditional Beckmann rearrangement process has been established to build cyano-containing ketones in the presence of photocatalyst. This novel transformation is remarkable with selective C-C bond cleavage and an oxidation process enabled by DMSO used as the solvent, oxidant, and oxygen source avoiding acid, base and toxic cyanide salts as the cyano source. Further applications in late-stage modification of complex and chiral molecules have also been reported.

Visible‐Light‐Photosensitized Aryl and Alkyl Decarboxylative Functionalization Reactions

“…Although the SET reduction by [Ir-F]* is not viable (E 1/2 III*/IV = À0.89 Vv s. SCE), the thermodynamic feasibility of an undesired electron transfer process between [Ir-F] (E 1/2 III/II = À1.37 Vv s. SCE) and 1a (E 1/2 red = À1.4 Vv s. SCE) [9a] prompted us to search for more suitable N-hydroxy esters with even lower reduction potentials to ensure that only an energy transfer mechanism can be operative.I nt his regard, we focused our attention on different oxime esters owing to their higher redox stability. [25] Promisingly,w hen acetophenone-derived 1b was employed under identical conditions,t he desired decarboxylated product 2 was obtained in 41 %y ield (Table 1, entry 2). Encouraged by this finding,w eevaluated as eries of aldoxime and ketoxime esters as activating groups (see Table 1).…”

“…Encouraged by this finding,w eevaluated as eries of aldoxime and ketoxime esters as activating groups (see Table 1). Aliphatic ketoxime 1cdid not undergo decarboxylation (entry 3), [25] but aromatic aldoximes (1d, 1e)a nd ketoximes (1f-1i)w ere found to be effective with varying levels of success (entries 4-9). Finally,a ni deal balance between redox stability,e ase of sensitization, and practicality was observed with 4,4'-difluorobenzophenone oxime ester 1j,w hich provided the desired deuterated product 2 in 82 %y ield (entry 10).…”

“…This is largely due to the inherent electronegativity bias of the unsymmetrical s-bonds,which generally leads to af acile SET process (either reductive or oxidative) outcompeting EnT reactivity in the presence of ap hotocatalyst. [25] Indeed, as eries of transformations were achieved by exploiting the N-centered radical generated from the bondpolarity-driven SET reduction of the NÀObond of hydroxylamine-derived activated esters,yielding astabilized benzoate species as the leaving group (Scheme 1d). [26] In contrary, bypassing the SET pathway by an EnT pathway could lead to ac oncerted fragmentation/decarboxylation process to generate the desired aryl radical.…”

Visible‐Light‐Photosensitized Aryl and Alkyl Decarboxylative Functionalization Reactions

“…To date, visible‐light‐induced energy transfer from excited photocatalysts has not been exploited to sensitize and cleave unsymmetrical σ‐bonds (Scheme c). This is largely due to the inherent electronegativity bias of the unsymmetrical σ‐bonds, which generally leads to a facile SET process (either reductive or oxidative) outcompeting EnT reactivity in the presence of a photocatalyst . Indeed, a series of transformations were achieved by exploiting the N‐centered radical generated from the bond‐polarity‐driven SET reduction of the N−O bond of hydroxylamine‐derived activated esters, yielding a stabilized benzoate species as the leaving group (Scheme d) .…”

Radical‐Promoted C−C Bond Cleavage: A Deconstructive Approach for Selective Functionalization

“…Jiao,S hi, and co-workers reported ap hotoinduced deconstruction/ oxidation of unstrained cycloketoxime esters (33). [57] It was suggested that, upon the b-fragmentation process,t he generated alkyl radical would be able to reduce the photocatalyst, thus forming ac arbocation intermediate (AI;S cheme 14), which should undergo oxidation with DMSO to give the ketone product 34.A sa ni llustration of its synthetic utility, the method was applied for the selective deconstruction/ oxidation of the estrone-derived product 34 a,a nd the synthesis of enantiopure cyano-containing ketone products (34 b and 34 c). Later,i tw as discovered that by using DMF as as olvent instead of DMSO,afragmentation/rearrangement took place involving the "leaving group" in an intermolecular recombination to give 35 (Scheme 14).…”