Chromium–Salen Complex / Nitroxyl Radical Cooperative Catalysis:A New Combination for Aerobic Intramolecular Dearomative Coupling of Phenols

Abstract

Herein we describe an aerobic intramolecular dearomative coupling reaction of phenols using a catalytic system with the combination of a chromium–salen (Cr–salen) complex and a nitroxyl radical. This novel catalytic system enables the construction of a spirocyclic dienone product, which is a potentially useful intermediate for the synthesis of various natural products such as alkaloids and phenylpropanoids from bisphenol in good yield under mild reaction conditions (under O2 and ambient temperature). A preliminary mechanistic study suggests that this reaction system is promoted by a cooperative electron transfer between the Cr(III)–salen complex, nitroxyl radical and bisphenol substrate.

On the Reaction Mechanism of the Selective C(sp3)–H Functionalization of N-Benzylpiperidines Mediated by TEMPO Oxoammonium Cation

“…Treatment of 8 and 9 with cation A under the established standard conditions gave -alkoxyamino-2,3epoxyamides 13 and 14 in good and moderated yield, respectively. Evidently, an unprecedented tetra [two C(sp 3 )-H and another two C(sp 2 )-H bonds] oxidation reaction occurred in a tandem fashion (Scheme 5, Eq. 2).…”

“…1,2 However, its use for the C-H oxidation of amines, particularly in cyclic amines, has been practically limited to either benzylic or allylic amines. 3 In this regard, during the last six years our research group has developed, from simple saturated tertiary cyclic amines and under transition-metal-free conditions, a series of C-H oxidation reactions of cyclic amines to bioactive alkaloids or advanced alkaloid intermediates. 4 These strategies are grounded on a selective and dual C(sp 3 )-H functionalization of tertiary piperidines and pyrrolidines mediated by TEMPO and sodium oxychloride reagents (Na-ClO 2 and NaClO).…”

“…3 In this regard, during the last six years our research group has developed, from simple saturated tertiary cyclic amines and under transition-metal-free conditions, a series of C-H oxidation reactions of cyclic amines to bioactive alkaloids or advanced alkaloid intermediates. 4 These strategies are grounded on a selective and dual C(sp 3 )-H functionalization of tertiary piperidines and pyrrolidines mediated by TEMPO and sodium oxychloride reagents (Na-ClO 2 and NaClO). 5 The proposed reaction mechanism states that the first C-H oxidation is initiated by the interaction of the oxoammonium cation A (formed by oxidation of TEMPO radical with either NaClO 2 or NaClO) with the tertiary cyclic amine 1 enabling the formation of cyclic iminium ion B which is spontaneously converted into enamine intermediate C. Finally, oxoammonium cation A reacts with C to generate another iminium intermediate D, which is trapped by chlorite anion to form unstable intermediate E which produces alkoxyamino lactam 2 after elimination of hypochlorite (Scheme 1).…”

“…A third question is connected with how TEMPO oxoammonium ion (A) approaches directly toward the C-H bond promoting the departure of a hydride atom to form an iminium cation B plus TEMPOH (Scheme 2, route C). 3,8 In this context, it is important to mention that it has been experimentally proved, with chiral N-benzylpiperazines, that iminium B is not formed from iminium F (Scheme 2, route D). 9 On the other hand, experimental evidence of the transient formation of enamine intermediate C depicted in Scheme 1, which undergoes electrophilic addition of the oxoammonium ion A to iminium intermediate D, is also provided.…”

Laccases from Pleurotus ostreatus Applied to the Oxidation of Furfuryl Alcohol for the Synthesis of Key Compounds for Polymer Industry

“…Moreover, pH also influences the TEMPO efficiency in oxidizing the substrates: under acidic conditions, a bimolecular hydride transfer is reported as the main oxidative mechanism, while an alkoxide adduct is produced under basic conditions, with an oxoammonium species as intermediate. [29] Despite the full mechanism still remains incompletely understood, it has been shown that under basic conditions these reactions are considerably faster than under acidic ones. [30] Nevertheless, basic pH has not been often applied for laccase-TEMPO mediated oxidations, since under these conditions most of the tested enzymes are not very active.…”