Oxidation aminoalcohol

Precursors of imidazoquinoxalines-compounds 109a, b and 112-have been synthesized from chloroquinoxalines 128 and corresponding amines in the presence of EtsN. To oxidize aminoalcohols 112 to ketones 114, different oxidative systems have been used a complex of trimethylamine and sulfuric anhydride in DMSO, chromium(VI) oxide in pyridine (Sarett method) (Luzzio 1998 Caamano et al. 2000), and dichloroxalate in DMSO (Swern method) (Scheme 4.58) (Ohmori et al. 1997 Parra et al. 2001 Deleuze-Masqudfa et al. 2004). 

Reactions of enamines with aluminum hydrogen dichloride (540,541) (UAIH4 and AICI3) or aluminum hydrogen dialkyl compounds (542) led to organoaluminum intermediates which could be hydrolyzed to tertiary amines or oxidized to aminoalcohols. The formation of olefins by elimination of the tertiary amine group has also been noted in these reactions. 

Treatment of the piperidine 74, obtainable from an aminonitrile such as 73, under N-methylation conditions leads to the dimethylamino derivative 75. The carbobenzoxy protecting group is then removed by catalytic hydrogenation. Reaction of the resulting secondary amine 76 with cyclohexene oxide leads to the alkylated trans aminoalcohol. There is thus obtained the anti-arrhythmic agent transcainide (77) [18]. 

These results support our hypothesis that there is a retroaldol like cleavage of 3-hydroxynitrosamines which occurs in biological systems. Our results agree with the data of Kruger, Preussmann, and Blattmann. The fact that the tertiary nitros-aminoalcohols undergo the cleavage as well as their secondary counterparts demonstrates that oxidation to a ketone is not a... 

The synthesis of aldehydes and ketoamides was performed on solid phase as well as in solution (Scheme 2.2). A semicarbazone linker (6) was employed for the assembly of the aldehydes on solid phase whereas the corresponding aminoalcohol was coupled in solution to the tripeptide and oxidized to the aldehyde, which produced epimeric mixtures [137]. For the synthesis of the ketoamides, hydroxyester THP resins were used as solid support ((7), Scheme 2.2) [138]. In solution the peptide bond was formed using an aminohydroxycarboxylic acid building block [138, 147]. Oxidation of the free hydroxyl group yielded the final inhibitors ((8), Scheme 2.2). 

The oxidative dehydrogenation of aminoalcohols has received little attention in the non-patent literature. Yang et al. (7) recently made a kinetic study of the dehydrogenation of ethanolamine to glycine salts... 

A rich family of 2-alkoxycarbonyl-l,3,2-oxazaphospholidine-2-oxides 179-181 was prepared from the reaction of camphor derived aminoalcohols 177 and 178 with either methoxycarbonyl phosphonic dichloride or ethyl dichlorophosphite followed by the reaction with methyl bromoacetate. The reaction with aminoalcohol 177a afforded the phosphorus epimers 179 and 180, in ratios from 1/1 to 12/1 depending on the iV-substituent which could be separated easily by column chromatography. The reaction with aminoalcohols 178a-c, however, gave a single epimer 181a-c in each case (Scheme 50) [81]. 

The 1,3-dipolar addition to terminal alkenes of nitrile oxides, generated from nitromethylene derivatives of bicycloheptane, provides 9,ll-ethano-13,15-isoxazolinoprostanoids, PGH analogs, with alkyl, phenyl, or additional heterocyclic fragment in the oo-chain (461). Chemical transformations of 9,11-ethano-13,15-isoxazolinoprostanoids furnish prostanoids with bifunctional fragments of P-hydroxyketone and a-aminoalcohol in the oo-chain. The reaction of P-hydroxy ketones with methanesulfonyl chloride gives rise to prostanoids with an enone component in the oo-chain. 9,ll-Ethano-16-thiaprostanoids have been prepared, for the first time, by nucleophilic addition of thiols to the polarized double bond in the oo-chain. The 1,3-dipolar addition to terminal alkenes of nitrile oxides, generated from nitromethylene derivatives of bicycloheptane provides 9,ll-ethano-13,15-isoxazolinoprostanoids with an alkyl, phenyl, or additional heterocyclic fragment in the oo-chain (462). 

Oxidative carbonylation is not necessarily associated with C - C bond formation. Indeed, heteroatom carbonylation may occur exclusively, as in the oxidative carbonylation of alcohols or phenols to carbonates, of alcohols and amines to carbamates, of aminoalcohols to cyclic carbamates, and of amines to ureas. All these reactions are of particular significance, in view of the possibility to prepare these very important classes of carbonyl compounds through a phosgene-free approach. These carbonylations are usually carried out in the presence of an appropriate oxidant under catalytic conditions (Eqs. 31-33), and in some cases can be promoted not only by transition metals but also by... 

In the course of biogenesis-type syntheses of lupin alkaloids, reduction of protected macrocyclic acyloin 50 (Scheme 15) has been found to be a second route to bicyclic aminoalcohol 14a (69JA7372). Another 11-membered ring compound, namely caprinolactam (51), on anodic oxidation in the presence of halide ions produces 6/7 bicyclic lactam 52 together with two isomeric 5/8 bicyclic lactams (87CJC2770). 

Aminoalcohol Ring Cleavage of Nitrile Oxide Cycloadducts Synthesis of... 

Aminoalcohol Ring Cleavage of Nitrile Oxide Cycloadducts Synthesis of Amino Polyols, Amino Sugars, and Amino Acids... 

Precursors of type E (erythro fragment) (Scheme 6.69) were obtained by cycloaddition of a nitrile oxide dipole to a-alkoxyalkenes. This strategy was used in the syntheses of dl- and D-hvidosamine (298) (Scheme 6.73). Fithium aluminum hydride reduction of the erythro adduct 130 produced aminoalcohols 135 in a 78 22 ratio (2,4-erythro/threo) in high yield. The mixture was subjected to HCl hydrolysis to give the hexosamine hydrochlorides 136, which after several steps, produced D-hvidosamine 137 possessing the D-ribo configuration (298). 

Syntheses with Intramolecular Nitrile Oxide Cycloaddition and Isoxazoline Reduction to the y-Aminoalcohol... 

Few examples of total syntheses have been reported that involve an intramolecular nitrile oxide cycloaddition and ensuing reduction to an aminoalcohol. The very first example was reported by Confalone et al. (334) and involved a synthesis of the naturally occurring vitamin biotin (287). The nitro precursor 284 was easily prepared from cycloheptene. When treated with phenyl isocyanate-triethylamine, cycloaddition led to the all-cis-fused tricyclic isoxazoline 285 with high stereoselectivity (Scheme 6.102). Reduction with LiAlFLj afforded aminoalcohol 286 as a... 

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