Hydroxy amines from oxides

Rosenau, T. Mereiter, K. Jager, C. Schmid, P Kosma, P. Sulfonium ylides derived from 2-hydroxy-benzoquinones crystal and molecular structure and their one-step conversion into Mannich bases by amine A-oxides. Tetrahedron 2004, 60(27), 5719-5723. 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

The synthesis of the fluoroketone that combines the retroamide type bond (76) is shown in Scheme 5. The 2,2-difluoro-3-hydroxyester 11 from a Reformatsky reaction was converted to the primary amide 12 by treatment with ammonia in diethyl ether. Reduction of the amide with borane dimethyl sulfide and protection of the resulting amine gave the protected intermediate 13. For the preparation of peptides XIV and XV, the hydroxy function was oxidized to the corresponding ketone using pyridinium dichromate. 

Examples for the alkaline hydrolysis of acylated 2-amino groups are the formation of 6-bromo-l-methylpyrido[2,3-i/]pyrimidine-2,4(l//,3//)-dione (35) from 6-bromo-l-methyl-2-(pivaloylamino)pyrido[2,3-[Pg.151]

Oxidation of l,2,4-triazin-3-amine with peracetic acid affords 3-amino-l,2,4-triazin-5(2//)-one (5)239 while oxidation with potassium permanganate affords l,2,4-triazine-3,5(2/f,4/f)-dione (6, 49% in a one-pot reaction from glyoxal).232 On treatment of l,2,4-triazin-3-amine with peracetic acid or perfluoroacetic acid at 60 °C, 3-amino-2-hydroxy-l,2,4-triazin-5(2/f)-one (7, 22%) is isolated.238 Treatment of 5,6-dimethyl-l,2,4-triazin-3-amine with potassium per-mangantate in basic or acidic media yields 3-amino-6-methyl-l, 2,4-triazin-5(2//)-one (8, 79%) as the sole product and not the 5,6-dione as reported earlier.232 The same product 8 can be isolated when 6-methyl-l,2,4-triazin-3-amine is oxidized with potassium permanganate, chromic acid or hydrogen peroxide in acetic acid.144,232,240... 

After the earlier work of Johnston and Overton, the alcohols (49) and (50) were obtained by borohydride reduction of (48), obtained from atisine. The a-alcohol (50) was purified by preparative t.l.c. and converted into the tosylate (51). On heating (51) with tetramethylguanidine in DMSO, an 85% yield of a mixture of isomers (52) and (53) was obtained. Compound (52) is identical with the product earlier prepared by pyrolytic rearrangement. Hydrogenation of (52) or (53) afforded the same dihydro-derivative. Deacetalization of (53) to the ketone (54) followed by reduction with lithium aluminium hydride afforded a mixture of the hydroxy-amines (55) and (56). These were treated with mercuric acetate to yield compounds (57) and (58). Jones oxidation of this epimeric mixture afforded compound (47). The structure of this compound was confirmed by an X-ray crystallographic analysis. 

The revised structure (4) has been determined for physoperuvine the free base is a mixture of bicyciic hydroxy-amine and monocyclic keto-amine tautomers. X-Ray diffraction methods have been used to characterise the unexpected product (5) from addition of nitrosobenzene to pyran-2-thione.12 the product (6) (from anchimerically assisted oxidative cyciisation of 5-amino-1-thiacydooctane using iodine in buffered methanol).13 the exo- and endo-1 -methylindene ozonides (7). 14 and the ozonide (8). 1 X-Ray studies confirm that the piperidine ring in 3-thia-7-aza-6.8-diphenylbicyclof3.3. llnonan-9-oi is boat-shaped 3 and that... 

Cytochrome P-450 Catalyzed Reactions - Studies with 02 have established that the cytochrome P-450 mediated hydroxylation of camphor by the bacterial enzyme and the enzyme purified from rat liver results in the incorporation of atmospheric oxygen in the 5-exo-hydroxylation product. Cumene [ 02]hydroperoxide will transfer its peripheral oxygen atom to a variety of compounds which serve as substrates for mammalian cytochrome P-450. As expected, 02 served as the oxygen source for the bacterial cytochrome P-450 catalyzed epoxidation of 5,6-dehydrocamphor.N-Hydroxy-methylcarbazole, formed by the cytochrome P-450 catalyzed oxidation of N-raethylcarbazole, incorporates 0 exclusively from dioxygen. Under anaerobic conditions cytochrome P-450 may catalyze the intramolecular transfer of oxygen present in tertiary amine N-oxides. Mechanistic studies on S-dealkylation and S-oxidation reactions also have used tracer methods. ... 

Three other TTC-negative metabolites isolated from Strain MIT-M-18 (754) were separated by HPLC and TLC. These compounds are oxidized with m-chloroperbenzoic acid to the corresponding hydroxy amine derivatives, namely, tryptoquivaline, nortryptoquivaline, and nortryptoquivalone, respectively. These three metabolites possessing a secondary amine in the molecule were designated as deoxytryptoquivaline (79), deoxynortryptoquivaline (80), and deoxynortryp-toquivalone (81), respectively. 

The results (Leete and Chedekel, 1974) indicate that 48% of [2- H](-)-nomicotine and 52% [2- C](+)-nomicotine is incorporated from the labeled nicotine. Thus if (+)-nornicotine is formed from (-)-nicotine, the transformation must involve the loss of the hydrogen from C-2 however, almost the same [ HA C]ratio occurs as in the administered mixture of [2 - H](-)-nicotine and [2 2- C](+)-nicotine, which indicates that in N. glauca (+)- and (-)-nicotine are demethylated at similar rates. If the demethylation had been stereospeciflc for (-)-nicotine, the resultant nomi-cotine would have its [ HA C]ratio doubled. This led the authors to propose a scheme for the formation of (+)-nicotine and (-)-nicotine (Figure 6.11). This mechanism accounts for the partial racemization of the nornicotine derived from (-)-nicotine a Cope elimination of nicotine N -oxide (a) would involve one of the hydrogens at C-3, which would provide the unsaturated compound (b). Elimination of water from this hydroxy amine yields the Schiff base (c), which upon hydrolysis yields formaldehyde or other Cl metabolite and the primary amine (d). Cyclization of this intermediate yields (+)- and ( )-nomicotine. Leete and Chedekel presume that these steps are enzyme mediated, and it is to be expected that the final cyclization would yield a preferential amount of (+)- or (-)-nornicotine however, the mechanism which yields (+)-nornicotine from (-)-nicotine remains unknown. 

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