Carbinolamines reduction

Presumably the species that undergoes reduction here is a carbinolamine an iminium ion derived from it or an enamme... 

At least two pathways have been proposed for the Nenitzescu reaction. The mechanism outlined below is generally accepted." Illustrated here is the indolization of the 1,4-benzoquinone (4) with ethyl 3-aminocrotonate (5). The mechanism consists of four stages (I) Michael addition of the carbon terminal of the enamine 5 to quinone 4 (II) Oxidation of the resulting hydroquinone 10 to the quinone 11 either by the starting quinone 4 or the quinonimmonium intermediate 13, which is generated at a later stage (HI) Cyclization of the quinone adduct 11, if in the cw-configuration, to the carbinolamine 12 or quinonimmonium intermediate 13 (IV) Reduction of the intermediates 12 or 13 to the 5-hydroxyindole 6 by the initial hydroquinone adduct 7 (or 8, 9,10). 

Amides can also be deacylated by partial reduction. If the reduction proceeds only to the carbinolamine stage, hydrolysis can liberate the deprotected amine. Trichloroac-etamides are readily cleaved by sodium borohydride in alcohols by this mechanism.237 Benzamides, and probably other simple amides, can be removed by careful partial reduction with diisobutylaluminum hydride (see Section 5.3.1.1).238... 

The carbinolamine-containing pyrrolo[2,l-c][l,4]benzodiazepine family of antitumor antibiotics is produced by various Streptomyces species well-known members include abthramy-cine, tomay mycine, and DC-81,138 Various approaches to the synthesis of these compounds have been investigated over past years reductive cyclization of suitably substituted nitroaldehydes is the frequently used method (Eq. 10.81).139... 

Cyclization of the Weinreb amide 356 under reductive conditions using lithium aluminium hydride (LAH) led to formation of the carbinolamine 357 which underwent elimination on treatment with methanesulfonic acid to give 358 in 72% yield as shown in Scheme 27 <2005TL249>. 

The first example of this type of transformation was reported in 1974 [76]. Three catalysts were investigated, namely [Co2(CO)8], [Co(CO)g/PBu ], and [Rh6(CO)i6]. The [Co OJg/PBu ] catalyst showed activity for reductive animation using ammonia and aromatic amines. The [Rh6(CO)16] catalyst could be used for reductive animation using the more basic aliphatic amines that were found to poison the cobalt catalyst. This early report pointed out that the successful reductive animation of iso-butanal (Me2CCHO) with piperidine involves selective enamine hydrogenation, that reductive animation of cyclohexanone with isopropylamine probably involves imine hydrogenation, and that reductive amination of benzaldehyde with piperidine would presumably involve the reduction of a carbinolamine. 

The second compound (accedine, C20H24N202, MP 148-149°C, [a]D +72°) showed no carbonyl absorption in the IR, and H-NMR and mass spectra were in full agreement with the almost total existence of ring-closed carbinolamine structure 23. The configuration at C-16 was determined by correlation with 32. Reductive methylation (CH20-H2/Pd) of 23 afforded 29, which on LiAlH4 reduction gave the diol 257 identical in all respects to the product obtained from... 

The absolute configuration of dichomine was determined by chemical correlation. Reduction with LiAlH4 in THF gave a product identical to (145, 20/ )-velbanamine (160) through sequential carbinolamine C—O reductive cleavage... 

In addition to encapsulation, the complex (93) also undergoes methylation, presumably by reduction of the carbinolamine formed from condensation of formaldehyde and (93) in a Caniz-zaro-type reaction (Scheme 51).223... 

Furthermore, in place of reduction of 10 it was possible to add organolithium reagents such that the resulting alkyl carbinolamine, after hydrolysis, gave either 12 or 13 depending upon hydrolysis conditions.6 In summary, these bicyclic lactams have provided a route to a variety of chiral, nonracemic cyclohexenones and cyclopentenones containing quaternary stereocenters. 

One of the starting materials, the bromoindolinemesylate 183 was obtained from the commercially available 5-hydroxyindole by mesylation followed by successive treatment of the resulting indole derivative with sodium cyanoborohydride and bromine. Coupling of 183 with the known boronic acid 184 in the presence of zero valent palladium complex led directly to the lactam 185, the intermediate carbinolamine 186 formed initially in the reaction suffering facile aerial oxidation during work-up. On reduction with sodium (2-methoxyethoxy)aluminium-hydride, the amide 185 yielded the aminophenol 187 which on chromatography underwent oxidative aromatisation to 182 in 54% yield. 

The Fischer cyclization of phenylhydrazones of structure (18) gives rise to the carbinolamine-lactones (19). Reaction with methylamine, followed by reduction, then affords a short synthesis of esermethole (20a) and eserethole (20b) (Scheme... 

Heyneatine is a carbinolamine ether of a new type, in which the oxygen atom is situated between C-3 and C-19 (n.m.r. spectrum). Since reduction (with LiAlH4) gives rise to (19S)-voacangarinol or (with NaBH4) to (19S)-voacangarine, the complete structure of (—)-heyneatine must be (167).81... 

Oxyberberine (49), when further oxidized by pyridine chlorochromate and then treated with methanol, gives the methoxy-ketone (50 R = Me) the tetra-methoxy-analogue of (49) behaves similarly.132 The carbinolamine (50 R = H) is obtainable, together with the keto-acid (53), by the photolysis of oxidoberberine (51), in the presence of oxygen and rose bengal, to produce the peroxide (52), followed by treatment with pyridine hydrochloride a tetramethoxy-analogue of oxidoberberine, prepared by the reduction of norcoralyne with zinc and acetic acid, followed by oxidation with a peracid, behaves in the same way.133... 

The sodium borohydride reduction of picraline furnishes a (noncrystalline) base which exhibits typically indoline UV-absorption, and which must therefore arise by reduction of the Va-carbinolamine ether linkage. Since this product still contains amethoxyl group, observed in the NMR-spectrum as a singlet at 6.28r, picraline does not possess a methoxyl group at C-2, and can therefore not have the structure LXXXVI. All these data, however, are consistent with the structure LXXIV (55)... 

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