Photo- and Metal-Mediated Deconstructive Approaches to Cyclic Aliphatic Amine Diversification

Abstract

Described herein are studies toward the core modificationof cyclicaliphatic amines using either a riboflavin/photo-irradiation approachor Cu-(I) and Ag-(I) to mediate the process. Structural remodeling ofcyclic amines is explored through oxidative C-N and C-Cbond cleavage using peroxydisulfate (persulfate) as an oxidant. Ring-openingreactions to access linear aldehydes or carboxylic acids with flavin-derivedphotocatalysis or Cu salts, respectively, are demonstrated. A complementaryring-opening process mediated by Ag-(I) facilitates decarboxylativeCsp(3)-Csp(2) coupling in Minisci-type reactionsthrough a key alkyl radical intermediate. Heterocycle interconversionis demonstrated through the transformation of N-acyl cyclic aminesto oxazines using Cu-(II) oxidation of the alkyl radical. These transformationsare investigated by computation to inform the proposed mechanisticpathways. Computational studies indicate that persulfate mediatesoxidation of cyclic amines with concomitant reduction of riboflavin.Persulfate is subsequently reduced by formal hydride transfer fromthe reduced riboflavin catalyst. Oxidation of the cyclic aliphaticamines with a Cu-(I) salt is proposed to be initiated by homolysisof the peroxy bond of persulfate followed by alpha-HAT from thecyclic amine and radical recombination to form an alpha-sulfateadduct, which is hydrolyzed to the hemiaminal. Investigation of thepathway to form oxazines indicates a kinetic preference for cyclizationover more typical elimination pathways to form olefins through Cu-(II)oxidation of alkyl radicals.