Visible-Light-Mediated Ring-Opening Strategy for the Regiospecific Allylation/Formylation of Cycloalkanols

Abstract

Here we describe a straightforward and efficient approach for regiospecific introduction of an allyl group into cycloalkanol molecules employing a visible-light-mediated ring-opening strategy. A wide range of distally allylated or formylated ketones is furnished from 1-aryl cycloalkanol precursors of variable ring sizes, providing a concise and practical access for the modification of complex natural products. Preliminary mechanistic studies demonstrate that the key O-centered radicals mediate the sequential ring cleavage and allylation/formylation.

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis

“…In 2018, Xia and co-workers detailed a method for the regiospecific ring-opening allylation and formylation of cycloalkanols ( Scheme 147 ). 440 The reaction system comprised similar conditions as those reported by Knowles, including the use of [Ir(dF(CF 3 )ppy) 2 (5,5′-d(CF 3 )bpy)]PF 6 ([ Ir-9 ]PF 6 ) photocatalyst and collidine Brønsted base under visible-light irradiation. 27 By employing Nozaki allyl sulfone reagents as electron-deficient radical acceptors, the authors demonstrated that a variety of arylcyclobutanols ( 147.1 – 147.4 ) and medium- to large-sized ring systems are amenable to ring-opening allylation, with 28 examples reported in yields of 31–90%.…”

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

“…During the last two years,Chen, Xiao and co-workers [55] as well as the group of Zhou group, [56] have reported anumber of studies on the photoinduced reductive fragmentation of Oacyl oxime derivatives.D espite the extraordinary advances achieved in reductive approaches,fragmentation of unstrained rings has so far been significantly overlooked. 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).…”

“…Xia and co-workers also reported as imilar methodology by using white light to achieve either deconstruction/allylation or deconstruction/formylation. [33] Seeking to overcome some of the limitations,Zuo and coworkers reported as trategy for the fragmentation of unstrained cycloalkanols,i ncluding secondary alcohols. [34] The key point in this strategy lies in the use of ac erium(III) chloride complex as aphotoredox catalyst, which behaves as an efficient ligand-to-metal charge transfer (LMCT).…”

Catalytic generation of alkoxy radicals from unfunctionalized alcohols

“…In 2018, the Yang group elaborated on this PCET system, demonstrating that the nascent alkyl radical formed aer b-scission can be captured by radical acceptors as part of an allylation protocol or oxidized by O 2 in air for subsequent formylation. 86 In 2019, the Knowles group expanded upon the use of PCET as a catalytic platform for O-H activation by reporting a general procedure for the ring-opening isomerization of cyclic aliphatic alcohols (Scheme 30). Unlike the previous protocol, this strategy no longer requires that substrates bear an oxidizable arene.…”