Electrochemistry of natural products. II. Electrolytic oxidation of some simple 1,2,3,4-tetrahydroisoquinoline phenols

Abstract

A series of derivatives of 1,2,3,4-tetrahydroisoquinoline has been oxidized electrolytically. Those containing phenol groups were dimerized to yield carbon-carbon dimers and carbon-oxygen-carbon dimers. Some of the variables such as the nature of the anode, the cell design, the solvent, the pH, and the reaction time were considered. The optimum conditions for the coupling of these phenols would seem to be oxidation of their sodium salts in CHsCN using tetraethylammonium perchlorate as supporting electrolyte and a graphite felt anode.The results of a number of experiments are presented. The products of the reactions depend strongly upon the relative location of the phenol group in the aromatic ring and the nitrogen in the heterocyclic ring. An explanation for this phenomenon is proposed.We have been interested in the electrolytic oxidations of phenolic tetrahydroisoquinolines8 as model compounds for some of the more important biosynthetic oxidation reactions. In the previous paper of this series,1 we studied the ratio of C-C dimers to C-O-C dimers as a function of the steric hindrance around the incipient bond between the isoquinolines. In this paper, we would like to present a more general and random study of some simple compounds.The compounds oxidized fell into several groups.Compounds 1-3 were nonphenolic and were examined to see how easily the various forms of the nitrogen ring were oxidized. Three oxygenation patterns were examined for the phenols themselves. The pattern in 4-6 is the most common one in nature.4 5The isomeric patterns in 7 and 8 and in 9 and 10 were chosen for comparison. Three possible nitrogen functions, 4-6, were studied for the natural system, and two were studied for the others. Compound 4, the alkaloid, corypalline,6 has been the starting point of several of our investiga-tions6 (Scheme I).Reaction Conditions. The Working Electrode. -The oxidation of 4 was studied in a two-compartment cell in aqueous systems with five different working electrodes. The results are given in Table I. The best yields at the lowest voltages were given on the Hg pool and graphite anodes. However, Hg failed to yield any product with the other phenols and was, itself, attacked in CH3CN solutions. Graphite felt was chosen as the anode for most of our work because of its high surface area and its low cost.Cell Design.-Two different cell designs were used. One was a two-compartment system and has been described.615 The other was a simple one-compartment system as described in the Experimental Section. Both worked well. However, when limited amounts of base were used, the base tended to concentrate in the cathode chamber of a two-compartment system and change the (1) (a) Paper I:

Preparative Electrolyses at Graphite Paste Anodes

“…Both systems have been used for the oxidative coupling of corypalline (7-hydroxy-6-methoxy-Nmethyl-l,2,3,4-tetrahydroisoquinoline) and related compounds in aqueous media, with yields comparable to those obtained at graphite cloth or graphite felt electrodes (7). In particular, the simplicity of construction of the GBC and the ease with which its paste layer can be renewed make this system potentially useful for general oxidative syntheses.…”

Anodic Electroorganic Chemistry and Natural Products

“…Another possible concerted reaction was observed in a study of the dimerization of simple phenolic tetrahydroisoquinolines (64). When the anion of N-methyl-6-methoxy-7-hydroxy-1,2,3,4-Downloaded by COLUMBIA UNIV on December 9, 2014 | http://pubs.acs.org Publication Date: January 1, 1989 | doi: 10.1021/bk-1989-0390.ch014 tetrahydrcisoquinoline, 68, was oxidized, a carbon-carbon dimer, 69 was isolated in 85 % yield.…”

Electrochemical strategies for C–H functionalization and C–N bond formation

“…[539][540][541][542][543] Seminal work on the intermolecular anodic oxidative coupling of phenols demonstrated that corypalline (210) could be electrochemically oxidized to the corresponding dimer (211, Scheme 63). [544][545][546][547][548] However, attempts to carry out the related intramolecular C-C coupling on laudanosine (212) resulted in oxidative dearomatization of one of the phenolic moieties and furnished O-methylflavinantine (213, Scheme 64). [549][550][551][552][553] Similar reactivity has also been observed for the related alkaloids amurine, oxocrinine, oxomaritidine and pallidine.…”