Enamides oxidative

Reactions of benzoylperoxide with morpholinocyclohexene and morpho-linocyclopentene furnished the corresponding a-benzoyloxyketones in modest yields (480,481). This oxidation has also been applied to some vinylogous amides (482), and the expected faster rate of reaction of the enamine system as compared with enamides has been noted in derivatives of 20-ketosteroids, in reactions with perbenzoic acid (59,483). 

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

Oxidative Heck arylation of enamides with arylboronic acids, using oxygen gas as a reoxidant for Pd(0) and 2,9-dimethyl-1,10-phenanthroline as a chelating regiocontrolling ligand, yielded a (= internally) arylated reaction product as the major compound with a very good a//3 selectivity [92]. Microwave irradiation with prepressurized sealed vials proved useful in reducing the reaction time (Scheme 82). 

Although several oxidative C—C bond cleavages have been observed, the only method useful for transformation is C-8—C-8a bond cleavage. Treatment of berberine (15) with m-chloroperbenzoic acid in dichloromethane in the presence of sodium bicarbonate at - 78°C gave polyberbine (66) and N-formylnoroxyhydrastinine (69, R1 + R2 = CH2) in 20 and 15% yield, respectively (Scheme 16) (54). Similar treatment of palmatine (64) and coptisine (65) led to polycarpine (67) and the enamide 68, respectively, in 40-50% yield (55). The yield of polyberbine was improved to 76% when.the oxidation was carried out in tetrahydrofuran in the presence of sodium hydride however, the yields of 67 and 68 could not be improved under the, same reaction conditions (56). The products were used for synthesis of tetrahydroprotoberberine (Section V,I,5) and aporphine alkaloids (Section V,J,3). 

A biomimetic synthesis of benzo[c]phenanthridine alkaloids from a protoberberine via the equivalent of a hypothetical aldehyde enamine intermediate has been developed (130,131). The enamide 230 derived from berberine (15) was subjected to hydroboration-oxidation to give alcohol 231, oxidation of which with pyridinium chlorochromate afforded directly oxyche-lerythrine (232) instead of the expected aldehyde enamide 233. However, the formation of oxychelerythrine can be rationalized in terms of the intermediacy of 233 as shown in Scheme 41. An alternative and more efficient... 

Oxidative conversion of palmatine, berberine, and coptisine to polycarpine, polyberbine, and its analog was described in Section II,B. These products were further transformed to aporphine alkaloids having a phenolic hydroxyl group at C-2 in the bottom ring (55). Hydrolysis with concomitant air oxidation of polyberbine (66) furnished 3,4-dihydrorugosinone, which was further air-oxidized in ethanolic sodium hydroxide to give rise to rugosinone (501) (Scheme 105). Successive reduction of the enamide 68 with lithium aluminum hydride and sodium borohydride afforded a mixture of ( )-norledecorine and (+ )-ledecorine (502). N-Methylation of the former with formaldehyde and sodium borohydride led to the latter. 

The pseudobenzylisoquinoline alkaloids are fairly widespread in nature, being found among members of Berberidaceae, Annonaceae, Fumariaceae, and Ranunculaceae. The biogenesis of the pseudobenzylisoquinoline alkaloids assumes their formation from protoberberinium salts by C-8—C-8a bond scission in a Baeyer-Villiger-type oxidative rearrangement to produce the enamides of type 73 and 74. These amides may be further biotransformed either to rugosinone (76) type alkaloids by hydrolytic N-deformylation followed by oxidation or to ledecorine (75) by enzymatic reduction. These transformations were corroborated by in vitro studies (80-82). It is suggested that enamide seco alkaloids may be precursors of aporphine alkaloids (80), on one hand, and of cularine alkaloids (77), on the other. 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

The tricyclic core of spirotryprostatin B can be formed via formation of the dihydropyrrole 325 <2000AGE4596>. Removal of the silyl protecting group of 322, followed by Dess-Martin oxidation, and reaction of the resultant aldehyde with the potassium salt of the diketopiperazine phosphonate 323 led to formation of the enamide 324. 

The photocyclization of enamides has been widely employed in the construction of heterocyclic systems the N-acryloyl-2-aminopyridines 37, for example, are converted on irradiation to the lactams 38.36 Numerous benzylisoquinoline alkaloids have been prepared using this approach, and in particular, the syntheses of benzo[c]phenanthridine alkaloids have been reviewed.37 Thus, irradiation of the [Z]-l-ethylidene-2-benzoyltetra-hydroisoquinoline 39 affords the corresponding 8-oxoberberine 4038 competing photoisomerization to the E-isomer is observed but cyclization occurs only via the Z-isomer. Examples of syntheses of Amaryllidaceae and indole alkaloids have also been reported. In this way, the precursor 41 of ( )-lycoran has been obtained by oxidative cyclization of the enamide 42.39... 

The difference between this catalytic system and Wilkinson s catalyst lies in the sequence of the oxidative addition and the alkene complexation. As mentioned above, for the cationic catalysts the intermediate alkene (enamide) complex has been spectroscopically observed. Subsequently oxidative addition of H2 and insertion of the alkene occurs, followed by reductive elimination of the hydrogenation product. 

Anodic amide oxidations have also proven useful for selectively converting amides into enamides that have in turn been used to functionalize the carbon beta to nitrogen. For example, the four-electron oxidation of carbamates was used to introduce a carbonyl beta to a nitrogen (Scheme 21) [50]. In this example, the starting carbamate was oxidized at a carbon... 

These reactions proceed via the a-acetoxy derivative, which then forms the en-amide. Furfrier oxidation of the enamide gives the isolated products. A synthesis of cu-pseudoconhydrine 29 from 2-propylpiperidine illustrates both this process and also the regioselectivity in oxidation of amides, which favours attack on a methylene rather than a methine carbon atom [126],... 

Synthesis of alkaloids enamide cyclizations for, 22, 189 (1983) lead tetraacetate oxidation in, 36, 70 (1989)... 

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