Oxidation of amino alcohols

It is significant that analogous transformations do not take place during oxidation of amino-alcohols of the pseudoheliotridane... 

Moffat oxidation of amino alcohols with EDC (Scheme 3.5) [20]. 

Moffat oxidation of amino alcohols with EDC(HCl)/DMSO excess EDO and the formed corresponding urea HC1 cation exchange resin anion exchange resincl [20]... 

IBX is also tolerant of amine functionality, and therefore is used for the successful oxidation of amino alcohols to amino carbonyls. Frequently, this synthetic transformation requires the protection of the amino group, as a nonhasic derivative, prior to oxidation. IBX also provides an alternative method to oxidize alcohols selectively in the presence of primary, secondary, or tertiary amines, although the in situ protonation of the amine with acid is usually required (e.g., trifluoroacetic acid, 1-1.5 equiv) to avoid reduced yields. Oxidation of an aminocyclohexanol occurs selectively upon treatment with both IBX and TEA (1 1 ratio), without degradation of the amine functionality, to give cyclohexanone in 91% yield (eq 3). ... 

DMP is especially useful for the oxidation of the optically active, epimerization-sensitive substrates without loss of enantiomeric purity [1224,1241,1242], In a typical example, DMP was found to be a superior oxidant for the efficient, epimerization-free synthesis of optically active N-protected a-amino aldehydes 879 from the corresponding N-protected 3-amino alcohols 878 (Scheme 3.353) [1224]. In contrast, the Swern oxidation of amino alcohols 878 afforded products 879 of only 50-68% ee. 

It is possible to protect aliphatic amines in the same manner. a-Amino acids may be prepared by the oxidation of -amino alcohols with potassium permanganate in dilute sulphuric acid [13], although the yields are inferior to those obtained when using the corresponding acylated derivatives [14]. 

Sasano Y, Nagasawa S, Yamazaki M, Shibuya M, Park J, Iwabuchi Y. Highly chemoselective aerobic oxidation of amino alcohols into amino carbonyl compounds. Angew Chem Int Ed Engl. 2014 53 3236-3240. 

Intramolecular nitrone cycloadditions often require higher temperatures as nitrones react more sluggishly with alkenes than do nitrile oxides and the products contain a substituent on nitrogen which may not be desirable. Conspicuously absent among various nitrones employed earlier have been NH nitrones, which are tautomers of the more stable oximes. However, Grigg et al. [58 a] and Padwa and Norman [58b] have demonstrated that under certain conditions oximes can undergo addition to electron deficient olefins as Michael acceptors, followed by cycloadditions to multiple bonds. We found that intramolecular oxime-olefin cycloaddition (lOOC) can occur thermally via an H-nitrone and lead to stereospecific introduction of two or more stereocenters. This is an excellent procedure for the stereoselective introduction of amino alcohol functionality via N-0 bond cleavage. 

Oxidative carbonylation generates a number of important compounds and materials such as ureas, carbamates, 2-oxazolidinones, and aromatic polycarbonates. The [CuX(IPr)] complexes 38-X (X = Cl, Br, I) were tested as catalysts for the oxidative carbonylation of amino alcohols by Xia and co-workers [43]. Complex 38-1 is the first catalyst to selectively prepare ureas, carbamates, and 2-oxazolidinones without any additives. The important findings were the identity of the counterion and that the presence of the NHC ligand influenced the conversions. 2-Oxazohdinones were formed from primary amino alcohols in 86-96% yield. Complex 38-1 also catalysed the oxidative carbonylation of primary amines to ureas and carbamates. n-Propylamine, n-butylamine, and t-butylamine were transformed into the... 

Homochiral hydroxyproline 139 served as the starting material for the synthesis of various bicyclic[5.5]hydantoins 140 (Scheme 19). The corresponding amino derivatives 142 were also available by oxidation of the alcohol 141 and reductive amination of the ketone followed by separation of diastereomers by silica gel column chromatography (Equation 19) <2005BML1161>. 

The oxidation of sulfamidites to sulfamidates is a way to prepare these heterocycles, although the direct reaction of amino-alcohols with sulfuryl chloride is generally more convenient <1990TA885>. The reduction of sulfamides leads to the corresponding diamines (Equation 3) <2005JA11250>. 

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

Acid hydrolysis of tetrahydrooxazines 407 is well known and widely used for the synthesis of amino alcohols 408 or for the enantioselective synthesis of aldehydes 409, which can be transformed to carboxylic acids by mild oxidation [78AHC(23)1 87JCS(P1)515, 87T4979 90JOC2114]. 

The oxidation of propargyl alcohol to the acid and of but-2-yne-l,4-diol to acetylene dicarboxylic acid is carried out on a technical scale at a lead dioxide anode in sulphuric acid [4, 5]. Electrochemical oxidation of acetylenic secondary alcohols to the ketone at lead dioxide in aqueous sulphuric acid [4], gives better results than the cliromic acid based process of Jones [6], Oxidation of aminoalkan-1-ols to the amino acid at a lead dioxide anode in sulphuric acid is achieved in 31 -73 % 5delds [7]. This route is applied to the technical scale production of (l-alanine from 3-aminopropanol in an undivided cell [8]. 

Minisci and coworkers followed Ishii s procedure, and implemented it in the oxidation of benzyhc alcohols to benzaldehydes in almost quantitative yields" (Table 12). A,Af-dimethylbenzylamines were converted into aldehydes in good yields, by using catalytic amounts of either HPI or A-hydroxysuccinimide (HSI) for the formation of the corresponding aminoxyl radical intermediates. Because the attempted oxidation of primary and secondary amines caused the degradation of catalyst HPI, protection of the amino group in those substrates by acetylation was considered. This led one to develop... 

Cyclic phosphonamides (tetrahydro-2//-l, 3,2-oxazaphosphorine 2-oxides) were obtained by reaction of / -amino alcohols with benzylphosphonic dichloride in moderate yield. In the case of the 6-monomethyl derivative the diastereomers were separated by chromatography. Deprotonation with /erz-butyllithium followed by alkylation occurred in a highly stereoselective manner (d.r. 96 4-99 1), independent of the nature of the alkylating reagent, counterion and solvent, as demonstrated for the 6,6-dimethyl derivative6. 

The oxidation of various alcohols by the poly(e-carbobenzoxy-L-lysine)-Cu complex was studied by Welch et aL127. The polymer catalyst showed selectivity in oxidation by virtually excluding alcohols of bulky structure such as diisopropyl and diisobutyl carbinol while admitting simple alcohols arch as n-butyl, iso-butyl, and sec-butyl. It was suggested from structural studies that the selectivity of the polymer catalyst resulted from the highly complex geometry of the molecular cage formed by the helix and the amino acid side chain around the coordinated Cu. The... 

SCHEME 46. Kinetic resolution of amino alcohols by asymmetric oxidation. 

The amino aldehydes Boc-Ala-H, Boc-Leu-H, Boc-Phe-H, and Boc-Thr(Bzl)-H had a much higher enantiomeric purity when prepared by reduction of Weinreb amides compared to the identical aldehydes prepared by the Collins oxidation of the alcohols (Table 5). 1314-20 ... 

Semisynthetic enzymatic oxidation of peptide alcohols employs equine liver alcohol dehydrogenase. Amino alcohols with nonpolar side chains and Z-Om[CH2OH] worked as effective substrates while polar amino alcohols such as H-Arg[CH2OH] and H-Lys[CH2OH] failed as substrates. To attain complete oxidation, semicarbazide was present in the reaction mixture to immediately trap the aldehyde, and flavin mononucleotide was used to oxidize the NADH to NAD+, which serves to oxidize the alcohol 41] Configurational stability was confirmed by NMR spectroscopy as in the case of Ac-Phe[CH2OH], which was prepared by sodium borohydride reduction of Ac-Phe-H 4 1... 

The kinetics of oxidation of selected 7-amino acids125 and aliphatic aldehydes126 by trichloroisocyanuric acid (TCICA) in aqueous acetic acid-perchloric acid is first order in both TCICA and substrate. The kinetics of Ru(IH)-catalysed oxidation of aliphatic alcohols by TCICA in aqueous H0Ac-HCI04 are zero order in [TCICA], fractional order in alcohol and first order in Ru(IH).127... 

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 amino alcohols 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... 

Dehydrogenation of amino alcohols of type 88 affords cyclic compounds 89, the formation of which can be explained by an intramolecular nucleophilic attack of the hydroxyl group on the formed enamine salt328,329. Several cyclic330 and bicyclic331 enamines were prepared by mercuric acetate oxidation. 

Yet another transition metal-catalyzed route to indoles involves the use of aminoalcohol precursors, for instance 94, which could be efficiently converted to 6-chloroindole 95 (Equation 24). A plausible mechanism seems to feature an oxidation of the alcohol to an aldehyde functionality, which undergoes intramolecular condensation with the amino group <20020L2691>. 

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