Oxidation enamines

B. By Hydrolysis Reactions.—Details have appeared of the synthesis of dibenzophosphorin oxides (15) from 5-alkyldibenzophospholes, by reaction with methyl propiolate in the presence of water, and of confirmatory syntheses from phosphinic acid chlorides, as shown below. Evidence for the suggested mechanism of the ring-expansion reaction is presented. The hydrolysis of enamine phosphine oxides is an efficient, although somewhat indirect, method for the preparation of j8-ketoalkylphosphine oxides (16) [see Section 3(iii), for the preparation of enamine oxides]. Reasonable yields (48—66%) of trialkylphosphine oxides (17) have been obtained by the alkaline hydrolysis of the products from the pyrolysis at 220 °C of red phosphorus with alkyl halides, in the presence of iodine. 

Enamine oxidation (6,406) synthesis of vinblastine (3). Treatment of enamine (2) with thallium(III) acetate followed by NaBK, reduction affords vinblastine (3) in 30% overall yield from the N-oxide 1. In contrast, treatment of 2 with OSO4 followed by NaBH4 affords leurosidine (4) in 25% overall yield. Potier etal. argue that the transformation 2— 3 is governed by stereoelectronic factors, whereas steric approach control governs 2 — 4. These transformations may have biogenetic implications. 

Quinoline undergoes phase I metabolism to form an enamine oxide, a rapid transitional epoxide, which can then form DNA adducts. This epoxide is formed on the pyridine moiety of quinoline. Fluorination at position 3 completely prevents the mutagenicity of quinoline. The major metabolic enzyme is the CYP2E1 isoform with the primary end-product from this reaction being 3-hydroxyquinoline. 

An elegant work is reported concerning the oxidation of 2-alkyl and 2-benzylthia-zolium salts, in the presence of a base, with the scope of finding a structural relationship for the thiamine-bound intermediate which intervene in the oxidative decarboxylation of a-ketoacids catalysed by thiamin diphosphate-dependent enzymes. 2-Alkyl and 2-benzylthiazolium salts, which are not electroactive, can be transformed into electroactive species by treatment with the base (trimethylsilyl)amide. Subsequent anodic oxidation affords the corresponding symmetrical dimers, by an EC mechanism (Scheme 72). As expected, the stabilizing effect of the substituents R, R at the a-carbon on the radical cation follows the order H < Me < OMe. When R is aryl, electron-donating p-substituents again enhance the enamine oxidation. 

Chiral y-amino-acids (e.g. 180) have been prepared from the corresponding optically active /8-amino-acids by the addition of one carbon atom using the Arndt-Eistert reaction.w-Amino-acids are available from cyclic anhydrides by treatment with stannyl azide (to give an w-isocyanatocarboxylic acid) followed by addition of an alcohol. In contrast to simple enamines, oxidation of N-acyl-a-aminocrotonates with thallium nitrate leads to the corresponding a/8-dimethoxy derivatives. 

Methylene blue irradiation a-Diketones from enamines Oxidation with singlet oxygen... 

The unusual alkaloid 13j8-hydroxystylopine was synthesized from protopine which was first converted to dihydrocoptisine. Enamine oxidation then afforded the corresponding phenolbetaine which, upon reduction with sodium boro-hydride, provided exclusively 13jS-hydroxystylopine ... 

N,N -unsymmetrically disubstituted piperazines are attainable by catalytic hydrogenation of the appropriate enamine of N-alkylpiperazine 9, Enamines oxidized with Tl(OAc)3 form a-acetoxyketones in yields generally superior to those obtained by oxidation of the free ketone O. Allylamines on treatment with KNH2 on alumina isomerize to form high yields of the enamine. ... 

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