RuO4-mediated oxidation ofN-benzylated tertiary amines. Are amineN-oxides and iminium cations reaction intermediates?

Abstract

N-Benzylmorpholine, -piperidine, and -pyrrolidine (1A-C, resp.) are oxidised by RuO4 (generated m situ) at both endocyclic and exocyclic (benzylic) N-c~ methylene positions to afford lactams (and dioxo-derivatives) and benzaldehyde (and benzoyl derivatives), respectively. The N-oxides of 1A-C, formed by a minor side reaction, are not involved as intermediates. Control experiments showed the transient formation of endo-and exocyclic iminium cations trapped with NaCN as the corresponding nitriles. The proposed course of the RuO4-mediated oxidation of 1A-C involves the consecutive steps 1 a iminium cations + cyclic enamine ~ oxidation products. The endocyclic/exocyclic regioselectivity of the oxidation reaction lies between 0.8 (for 1A) and 2.1 (for 1B). The amine cation radical and the N-c~-C. carbon centered radical seem not to be involved. 9 Central European Science Journals. All rights reserved.

RuO4-mediated oxidation of N-benzylated tertiary amines. 3. Behavior of 1,4-dibenzylpiperazine and its oxygenated derivatives

“…As shown below, the oxidative patterns of 1, 7, or 9 were more complicated than those suggested in the literature [6]. Generally speaking, the respective reactions followed the same pathways as those already reported by us for other substrates [7,8]. Even more interesting was the behavior of 4 and of its oxygenated derivatives; the respective results will be detailed in a coming paper [9].…”

“…Oxidation was performed in the same conditions as above [2,3,7,8], that is with catalytic amounts of RuO 4 (generated in situ from catalytic RuO 2 and excess NaIO 4 ), in CCl 4 /water heterogeneous mixtures and at room temperature. The reaction mixtures were worked-up in two ways (A or B ; see Section 3.8), differing by the order of operations.…”

“…At variance with some of these data, our previous works, devoted to the RuO 4 -oxidation of tertiary amines of general structure Ph-CH 2 -NR 2 (NR 2 = 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl [7]; R = alkyl [8]), have indicated that both types of N -α-sites were attacked, even in the case of 1-benzylpiperidine. The reactions were interpreted as occurring through the corresponding iminium cations, as well as through enamines, generated by N + −β-deprotonation of the non-benzylic cations (R = CH 3 ).…”

RuO4-mediated oxidation of N-benzylated tertiary amines. 2. Regioselectivity for N,N-dimethyl- and N,N-diethylbenzylamine as substrates

“…1 The identified reaction products and the corresponding yields are shown in Table 1 (entries 1-4). To understand better the behaviour of 1A-B, several control experiments were performed also and the respective results are partly listed in Table 1 (entries 5-11).…”

“…In a previous paper 1 we studied the RuO 4 -mediated oxidation 2 of some N-benzylated cycloalkylamines and found that the attack occurs at both types of N-α-methylene positions, 3 i.e., endocyclic and exocyclic (benzylic). Proof of the incursion of the corresponding iminium cations as intermediates came from their capture as nitriles in the presence of cyanide anion (cyano trapping).…”