Aminoalcohol synthesis

Table 6.1. Variation of the aldehydes in the 1,3-aminoalcohol synthesis by using 2-phenylethyl-amine as constant building block...

General Concept and Further Applications for Diamine and Aminoalcohol Synthesis... 

The dlenophlle, 3-acetyl-2(3H)-oxazolane, Is an attractive Intermediate for the synthesis of vicinal aminoalcohols with cIs configurations. It reacts with 1,3-dienes, even under quite mild conditions, to form (4+2) cycloadducts. Its high reactivity with deactivated 1,3-dienes Is noteworthy. This property is present also in 2(3H)-oxa201one which can be obtained easily through solvolysis of 3-acetyl-2(3H)-oxa2olone In methanol. 3-Acetyl-2(3H)-oxazolone, on UV irradiation In the presence of a sensitizer, combines easily with olefins to form (2+2) cycloadducts, the hydrolysis of which leads to the class of cis-2-aminocyclobutanols. 

The Mannich reactions plays an important role in pharmaceutical chemistry. Many /3-aminoalcohols show pharmacological activity. The Mannich reaction can take place under physiological conditions (with respect to pH, temperature, aqueous solution), and therefore can be used in a biomimetic synthesis e.g. in the synthesis of alkaloids. 

Scheme 15 Parallel synthesis of 2-oxazolines from carboxylic acids and aminoalcohols using PS-Mukaiyama reagent...

Fluorinated dithioester 39 has also been involved in thioacylation reaction of enantiopure aminoalcohols leading to the corresponding hydroxylated thioamides. The later, treated either by SOCVpyridine, CH3SO2CI, or PhjP/DEAD, cyclise into thiazolines 42 without epimerisation and in excellent yields. An interesting application of this reaction is the synthesis of a new type of modified nucleotides such as 43 and 44 by a one pot reaction simply by mixing the dihydroxy substituted thioamide (obtained from 39 and the 2-amino-l,3-... 

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 stereochemistries of the reactions between 0-aryl 0-methyl phosphonochloridothioates and nucleophiles have been studied in relation to the synthesis of 1,3,2-oxazaphospholidines. No displacement of chlorine takes place on treatment of O-methyl 0-4-nitrophenyl phosphonochloridothioate with 2-methoxyethanol, and in the presence of 1-phenylethylamine, it is only the latter which reacts. In addition, when the same phosphonochloridothioate is treated with sodium ethoxide, it is the 4-nitrophenoxy group, rather than chlorine, which is displaced. Both displacements were shown to occur with inversion of configuration at phosphorus. The use of such an acid chloride as a two-step 1cyclophosphorylating1 agent of 2-aminoalcohols to give 1,3,2-oxazaphospholidines (209), is illustrated. ... 

Rao et al. [100] for the first time report the biomimetic approach for the synthesis of a single enantiomer of p-aminoalcohol. In this approach p-cyclodextrin formed by the inclusion of complex 77 with racemic aryloxyepoxide which reacted enantioselectively with amines imder solid state condition to give the product in 100% ee and 70-79% isolated yield. The yield which was above 50% was explained in terms of continuous racemization of the... 

Reddy L. R. Bhanumathi, N. Rao, K. R. (2000) Dynamis kinetic asymmetric synthesis of y -aminoalcohols from racemic epoxides in cyclodextrin complexes under solid state conditions., Chem. Commun. 2321-2322. 

Y. Yamamoto and co-workers used L-aspartic acid 4-methyl ester (108) as their starting material for the synthesis of preussin [64]. The ester was transformed in nine steps to the TBDPS-protected aminoalcohol 109 (Scheme 28). Allylation of the iST-Boc-protected amine using allyl bromide... 

More recently a rhodium-catalyzed enantioselective synthesis of duloxetine (3) has been reported (Scheme 14.17). In this work, readily available amino ketone 51 was converted to (6)-aminoalcohol 36 in 75% yield and greater than 99% ee. The intermediate alcohol was subsequently converted into duloxetine (3) in a single step via standard etherification. 

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... 

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... 

---