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

Abstract

N, and N,N-diethylbenzylamine (1B) underwent RuO 4 -mediated oxidation by attack at both types of (N-α)C-H bonds (i.e., alkyl and benzyl) to yield the corresponding Nalkyl-N-benzylamides [and N-methyl-(8A) or N-ethylbenzylamine (8B), resp.] and benzaldehyde (and N,N-dialkylbenzamides), respectively. Oxidation of 8A-B occurred also, as well as their reaction with formaldehyde or acetaldehyde, respectively, equally formed during the oxidation of 1A-B or 8A-B. Initial formation of the iminium cations from 1A-B was proved by their capture as nitriles. The statistically corrected alkyl/benzyl regioselectivity of the oxidation reaction was 4.1 for 1A and 2.1 for 1B. Comparison with the results obtained on Nbenzylpiperidine showed that RuO 4 does not discriminate axial and equatorial CH bonds in the piperidine ring. The N-α-C . carbon-centered radical and the amine cation radical seem not to be involved as precursors of the iminium cations.

The Chemoselective Reduction of Isoxazolineγ-Lactams Through Iminium Aza-Diels-Alder Reactions: A Short-Cut Synthesis of Aminols as Valuable Intermediates towards Nucleoside Derivatives

“…The regioselectivity of the oxidation of N -benzylated tertiary amines has already been presented by Petride and coworkers [ 34 , 35 ]. In the case of the tricyclic 2-azanorbornane derivatives at hand, two different methylenes ( exo cyclic and endo cyclic) are activated by the same nitrogen atom and the oxidation reaction proceeds with poor regioselection and both the methylenes are involved affording two different amides [ 36 , 55 ].…”

“…Since its introduction into organic chemistry more than fifty years ago [ 32 ], RuO 4 -catalyzed reactions in a biphasic system were often considered to be sluggish or unselective [ 33 ]. Two recent papers by Petride and coworkers [ 34 , 35 ] dealing with the RuO 4 -mediated oxidation of N -benzylated tertiary amines (cyclic and acyclic) prompted us to test the RuO 4 on our tricyclic isoxazolino-2-azanorbornene derivatives of type 2 probing the regioselectivity of the oxidation process without replacing the benzyl group at the nitrogen atom or any other structure modification activating the adjacent methylene towards oxidation. This strategy was considered in view of the strong oxidative ability of RuO 4 .…”

RuO4-Mediated oxidation of N-benzylated tertiary amines. Four- and three-membered azacycloalkanes as substrates

“…8 For simplicity, the desired entry (x) of Table 1 will be cited as T-x. Since free benzoic acid is always derived from benzaldehyde (BzH), [8][9][10]15,16 the amount quoted in Table 1 for BzH actually refers to the sum BzH+benzoic acid.…”

“…The powerful oxidant ruthenium tetroxide (RuO4) 1 is widely used to functionalize C-H bonds in various organic compounds, such as hydrocarbons, 2,3 halides, 4 ethers, 5 alcohols, 6 amines, [7][8][9][10][11][12] or amides. 13 Rarely, the oxidative attack takes place at a heteroatom, like in the transformation of sulfide into sulfone.…”

“…15,16 In addition, a less common 1,1dehydrogenation reaction transforms tertiary amines (R-CH2-NR2) to amides (R-CO-NR2), with iminium ions as intermediates. [7][8][9][10][11] Our previous research on oxidation of tertiary amines focused on the oxidative behaviour of medium-size azacycloalkanes, namely 1-benzylpiperidine (1a) and 1-benzylpyrrolidine (1b). 8 In this paper the studies are completed with the oxidation of small-ring analogues, 1-benzylazetidine (1c) and -aziridine (1d) (Scheme 1).…”