Electrooxidative methoxylation

Debenzylation of Ar-benzyl-6e/a-lactams 41 has been achieved by electrooxidative methoxylation of 41 at the benzylic position followed by hydrolysis with p-toluene-sulfonic acid in acetone 27>. For example, the electrolysis of A-benzyl-3-methylene-6e/fl-lactam 41 (R = OMe) in an MeOH E NClC —fPt) system in an undivided cell forms iV-methoxybenzyl-3-methylene-6efa-lactam 42 (R = MeO) in 54% yield (Scheme 2-14). The debenzylation of 42 is carried out on treatment with p-toluene-sulfonic acid in aqueous acetone to give 3-methylene-6e/a-lactam 43 in 50% yield. 

We have also examined the use of higher ultrasonic frequencies (500 kHz and 800 kHz) and found the trend in product distribution from carboxylate electrooxidation at platinum electrodes in methanol to be the same as under sonication in the 20 kHz to 40 kHz frequency range. However, we obtained better yields in spite of the usual reduced cell voltage requirements in the presence of ultrasound. There also seemed to be fewer of the numerous low-yield methoxylated species and other side-products. 

A synthetic method of introducing a methoxy group into the alpha position of alpha-amino acid derivatives and a/p/ia-amino-fern-lactams has been exploited by employing an indirect electrooxidation process 23). For example, the electrolysis of the lactam 33a in a MeOH—NaCl—(Pt) system yields the methoxylated lactam 34a in 92% yield. The indirect methoxylation of fern-lactams proreeds successfully without cleavage of the azetidinone ring (Scheme 2-11). 

Electrooxidation of n/p/ia-dihydroionol in an MeOH—LiCIO —(C) system at 1.25 V (SCE) can lead to the corresponding methoxylated products in 57% yield, whereas the electrolysis in an MeCN-l,6-Lutidine—(Pt) system at 1.6 V (Ag/Ag+) resulted in edulan derivatives in ca. 23% yields. The electrolysis of ieto-dihydroionol in either an MeOH—LiC104—(C) or an MeCN—H20—(Pt) system gives spiro compounds including 6-methoxy- and 6-hydroxydihydrotheaspiranes and theaSpirane in 21-23% yields77). 

In the case of branched C-terminal amino acids, methoxylation at the C-terminus is accompanied by formation of imidazolidine-4-ones by cx-oxidation at the C-terminus followed by intramolecular attack of the nitrogen of the N-terminal amino acid. Tliis reaction can be performed in high yields, if the electrooxidation is performed in aceto-nitrile/5% methanol [200]. 

When benzothiophene and its derivatives are oxidized in methanol/KOH at a Pt anode, 2,3- and 4,7-methoxylated products are obtained [212, 213], and it was shown that their formation is temperature dependent [213]. The electrooxidation of benzothiophene and 2-methyl- and 3-methyl-benzo[Z ]thiophene in methanol containing NaCN leads to heterocyclic ring-substitution products [214]. 

A. Olefinic compounds Acetylenic compounds Aromatic compounds Carbonyl compounds F/c-Oxygen compounds Nitrogen compounds Sulfur compounds Halogen compounds Other heteroatom compounds Organometallic compounds Stereoselective and Stereospecific Electrooxidation A. Carboxylic acids Acetoxylation Methoxylation Acetamidation... 

SCHEME 2.1 General scheme of methanol electrooxidation considering series and parallel pathways to form carbon dioxide as the product. Solid and dashed arrow lines indicate the demonstrated and possible reaction pathways, respectively. Path 1 denotes the formyl intermediate mechanism and Path 2 the methoxyl intermediate mechanism. 

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