Oxidative C-C Bond Cleavage of N-Protected Cyclic Amines by HNO3-TFA System

Onomura, Osamu; Yamamoto, Kosuke; Toguchi, Hiroyuki; Harada, Tomohiro; Kuriyama, Masami

doi:10.3987/com-19-s(f)31

Cited by 1 publication

(1 citation statement)

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“…We have found oxidative pathways to be particularly effective for the deconstructive functionalization of cyclic aliphatic amines (saturated azacycles). , In complementary approaches, others have demonstrated oxidative bond cleavage of cyclic amines under aerobic conditions − as well as through the use of metal-oxo species. − While these strategies provide effective ways to achieve diversity in cyclic amine transformations, metal-oxo catalysts tend to favor oxidative pathways leading to imide products; peripheral modification is favored over core modification for these catalysts. Our goal was to develop a straightforward, distinct approach that would achieve a reconfiguration of the cyclic amine skeleton through structural transformations beyond ring opening.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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Described herein are studies toward the core modification of cyclic aliphatic amines using either a riboflavin/ photo-irradiation approach or Cu(I) and Ag(I) to mediate the process. Structural remodeling of cyclic amines is explored through oxidative C−N and C−C bond cleavage using peroxydisulfate (persulfate) as an oxidant. Ring-opening reactions to access linear aldehydes or carboxylic acids with flavin-derived photocatalysis or Cu salts, respectively, are demonstrated. A complementary ringopening process mediated by Ag(I) facilitates decarboxylative Csp 3 −Csp 2 coupling in Minisci-type reactions through a key alkyl radical intermediate. Heterocycle interconversion is demonstrated through the transformation of N-acyl cyclic amines to oxazines using Cu(II) oxidation of the alkyl radical. These transformations are investigated by computation to inform the proposed mechanistic pathways. Computational studies indicate that persulfate mediates oxidation of cyclic amines with concomitant reduction of riboflavin. Persulfate is subsequently reduced by formal hydride transfer from the reduced riboflavin catalyst. Oxidation of the cyclic aliphatic amines with a Cu(I) salt is proposed to be initiated by homolysis of the peroxy bond of persulfate followed by α-HAT from the cyclic amine and radical recombination to form an α-sulfate adduct, which is hydrolyzed to the hemiaminal. Investigation of the pathway to form oxazines indicates a kinetic preference for cyclization over more typical elimination pathways to form olefins through Cu(II) oxidation of alkyl radicals.

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