Secondary amino ketone alcohols

Zhang and colleagues [26] synthesized the Duanphos enantiomers 57 and 58, and reported on the Rh-Duanphos-catalyzed highly efficient hydrogenation of a series of /9-secondary-amino ketones with ee-values of up to >99%, and with turnover numbers (TONs) of more than 4500 (Table 33.7). This hydrogenation provides a potentially practical synthesis for key pharmaceutical intermediates. The y-secondary amino alcohols are of particular interest to synthetic chemists as they are key intermediates for the synthesis of an important class of antidepressants, 59-62 [32]. 

Chiral amino alcohols are common structures in drug molecules for example, y-secondaiy aminoalcohols are key intermediates in the synthesis of several pharmaceuticals, examples of which are shown in Scheme 14.12. Zhang has shown that Rh-DuanPhos catalysts can be used to synthesise these key intermediates directly via asymmetric hydrogenation of the p-secondary amino ketone. Application to the synthesis of the antidepressant duloxetine is shown in Scheme 14.12. It should be noted that, to date, ruthenium catalysis has not been successfully applied to the reduction of secondary amino substrates a tertiary amino group is required resulting in a less efficient synthesis requiring extra S3mthetic steps. ... 

Lutz, R. E., J. A. Freek, and R. S. Miirphey Secondary and tertiary amino ketones and alcohols derived from desoxybenzoin and 1,2-di-phenylethanol. Ring-chain tautomerism of the a-(p-hydroxyethyl-amino)-ketones. J. Amer. chem. Soc. 70, 2015 (1948). 

Pyrrolizidine alcohols are readily oxidized. Stereoisomeric 1-hydroxymethylpyrrolizidines when oxidized with chromic acid afford stereoisomeric pyrrolizidine-1-carboxylic acids (see Section III, C).81,90 Secondary alcohols, when subjected to Oppenauer oxidation or chromic acid treatment, yield amino-ketones (cf. refs. 72, 77, and 81). 

This nucleophilic reactivity of 2-aminothiazoles has been used to prepare biheterocyclic compounds. Thus 2-aminothiazole reacts with chlorovinyl methyl ketone yielding 5-methyl-thiazolo[3,2-a]pyrimidinium chloride (Scheme 109). In the presence of formaldehyde, aminothiazoles react with ends affording condensation products, through the intermediacy of Mannich bases (Scheme 110). In acidic medium and at higher temperatures, condensation of 4-aryl-2-aminothiazole with benzaldehyde takes place at the C-5 position (Scheme 111). The same orientation is observed when 2-amino-4-methylthiazole is alkylated by secondary or tertiary alcohols in 85% sulfuric acid (Scheme 112). 

Secondary or tertiary p-amino alcohols can be obtained by reduction of a-amino ketones with K-glucoride best results were obtained starting from aromatic a-amino ketones (44-73% ee), while aliphatic amino ketones gave only low enantioselec-tivity (9-33% ee). Interestingly, the amino alcohols obtained are enriched in the (S) enantiomer and the enantioselectivity increases with the bulkiness of the substituents on the amino group. 

The Maillard reaction and the oxidation of lipids are two of the most important reactions for the formation of aromas in cooked foods. Interactions between lipid oxidation and the Maillard reaction have received less attention, despite the fact that lipids, sugars, and amino acids exist in close proximity in most foods. Lipids, upon exposure to heat and oxygen, are known to decompose into secondary products, including alcohols, aldehydes, ketones, carboxylic acids, and hydrocarbons. Aldehydes and ketones produce heterocyclic flavor compounds reacting with amines and... 

The N—0 bond in the tetrahydro-2,3-benzoxazepine (27) can be cleaved reductively either directly using zinc in acetic acid to give (29) or stepwise via the methiodide salt (28) to give (30). The secondary amino alcohol (29) can be converted readily to (30) (Scheme 1). The N—O bond in (28) can also be broken under basic conditions in a Hofmann-like elimination to afford the amino ketone (31) (Equation (2)) <80AJC833>. 

DMP with high purity by the original procedure therefore, a few modifications have been suggested. In addition, DMP has been successfully used in the syntheses of polycyclic heterocyclesand in the removal of thioketals and thioacetals. It should be mentioned that other hypervalent iodine compounds can be used as oxidants as well, especially for the o-iodoxybenzoic acid (IBX), the precursor to DMP, which can oxidize tertiary cyclic allyl alcohol into O, y0-unsaturated cyclic ketones and secondary amines into imines and can convert epoxides or aziridines into corresponding of-hydroxy ketones or Q -amino ketones. 

Various enantiomerically pure aziridino ketones, e.g. 1814, have been prepared from the corresponding secondary alcohols 1813 by Swern oxidation. The configurationally stable a-amino ketones were stereoselectively reduced by L-Sdectride to provide the corresponding alcohols with high diastereoselectivities and in high... 

An unlimited number of binding sites exist in proteins dissolved or dispersed in water (case b). K values for several aroma compounds are given in Table 5.38. The value of the constant decreases in the order of aldehydes, ketones, alcohols, while compounds such as dimethylpyrazine and butyric acid are practically unable to bind. In the case of aldehydes, it must be assumed that they can react with free amino- and SH-groups. The high values of K can refiect other than secondary forces. Bovine serum albumin and soya proteins are practically identical with regard to the binding of aroma compounds (Table 5.38). Since both proteins have a similar hydrophobicity, it is apparent that hydrophobic rather than hydrophilic interactions are responsible for aroma binding in proteins. 

Chemically bonded CSPs based on (18-crown-6) 2,3,1142-tetracarboxylic acid (ISCeTA, Fig. 10) are highly effective in the resolution of natural and unnatural a-amino acids (except for proline) [131-133], primary and secondary amino alcohols [134-136], P-amino acids [137], aryl a-amino ketone [138], and a-amino acid derivatives [20, 131], A number of pharmaceutically important compounds such as P-blockers [134, 135], fluoroquinolone antibacterial agents [139], amphetamine, phenylethanolamine, octopamine, and norepinephrine [132] were separated quite well on this crown ether CSP. 

Reaction With Carbonyl Compounds. Primary and secondary nitroparaffins undergo aldol-type reactions with a variety of aldehydes and ketones to give nitro alcohols (11). Those derived from the lower nitroparaffins and formaldehyde are available commercially (see Nitro alcohols). Nitro alcohols can be reduced to the corresponding amino alcohols (see Alkanolamines). 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Among the most active catalysts for the asymmetric transfer hydrogenation of prochiral ketones and imines to chiral alcohols and amines are arene-ruthenium(II) amino-alcohol (or primary/ secondary 1,2-diamine)-based systems, with an inorganic base as co-catalyst, developed by Noyori139-141 and further explored by others (Scheme 27).142-145... 

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