Chiral alcohols, primary

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... 

Chiral fl-amino esters. The conjugate addition of primary amines to alkyl crotonates proceeds in satisfactory yield when carried out under high pressure. French chemists have recently examined this reaction using crotonates derived from chiral alcohols. Thus addition of diphenylmethylamine to 8-phenylmenthyl croton-ate proceeds in 85-90% chemical yield and in 60% de. Optical yields are increased... 

Alkanes are preferentially hydroxylated at the more nucleophilic C—H bonds, with relative reactivities tertiary secondary primary hydrogens = 7000 110 l.303 This reaction occurs with a high retention of configuration at the hydroxylated carbon atom, as shown by the selective formation of cis-9-decalol from the oxidation of cis-decalin with chromyl acetate in an acidic medium304 and the hydroxylation of chiral (+)-3-methylheptane (91) to chiral alcohol (92) with 72 to 85% retention of configuration.305... 

In this case, the primary reaction is presented by the so-called citric acid cycle with the participation of various NAD+-dependent dehydrogenases synthesizing corresponding final products typical of this cycle. However, active intermediate NAD+H and H+ particles formed in the course of these reactions are able to induce reduction of aldehydes and ketones to corresponding chiral alcohols with the simultaneous regeneration of the NAD+ co-factor. 

A transaminase patented by Celgene Corporation (Warren, NJ), called an co-aminotransferase [(co-AT)E.C. 2.6.1.18] does not require an a-amino acid as amino donor instead it requires a primary amine and hence has the ability to produce chiral amines.125 126 A similar co-AT from Vibrio fluvialis has been described for the production of chiral amines along with chiral alcohols when coupled with AdH or chiral amino acids when coupled with an a-amino acid aminotransferase.127130 Another co-AT, ornithine (lysine) aminotransferase (E.C. 2.6.1.68), has been described for the preparation of a chiral pharmaceutical intermediate used in the synthesis of Omapatrilat, a vasopep-tidase inhibitor developed by Bristol-Myers Squibb, as well as the UAA A1 -piperidinc-6-carboxylic acid.131-132... 

Alcohok. When using the H NMR spectra of MTPA esters to determine the enantiomeric purity of alcohols, the MTPA methoxy peaks tend to be most useful. This technique can be sensitive enough to detect as little as 1% of the minor alcohol enantiomer. The enantiomeric purity of chiral alcohols (1) and (2) has been determined this way. The enantiomeric purity of primary alcohols (3) and (4), in which the asymmetric center is not the carbinol carbon, has also been determined by H NMR analysis of their MTPA esters. A slight variation of this methodology is the use of shift reagents like Eu(fod)3 to increase the chemical shift separation between diastereotopic MeO peaks this procedure has been used in the analysis of alcohols (S) and (6). ... 

There are a large number of different enzymes present in yeast. The primary ones responsible for the conversion of glucose to ethanol are discussed in Chapter 18. While this fermentation reaction is taking place, certain ketones can be reduced to chiral alcohols. 

Treatment of a primary aliphatic amine with nitrous acid or its equivalent produces a diazonium Ion which results in the formation of a variety of products through solvent displacement, elimination and solvolysis with 1,2-shift and concurrent elimination of nitrogen. The stereochemistry of the deamination-substitution reaction of various secondary amines was investigated as early as 1950, when an Swl-type displacement was suggested. Thus, the process can hardly be utilized for the preparation of alcohols except in cases where additional factors controlling the reaction course exist. Deamination-substitution of a-amino acids can be utilized for the preparation of chiral alcohols. 

Although prochiral or chiral alcohols and carboxylic acid esters initially served as the primary classes of substrates, compounds susceptible to processing via these two routes now encompass diols, a- and 3-hydroxy acids, cyanohydrins, chlorohydrins, diesters, lactones, amines, diamines, amino alcohols, and a-and 3-amino acid derivatives. Gotor and Arroyo have reviewed the use of biocatalysts for the preparation of pharma-eeutical intermediates and fine ehemieals. Some specific examples are indieated below. 

This procedure enabled versatile hydrolysis of pyrrohdinones followed by decarboxylation (Scheme 12.191) [347]. It has been disclosed that a neutral organotin dimer [tBu2SnOH(Cl)]2 is an efficient catalyst for deacetylation (Scheme 12.192) [348]. When an MeOH solution of an acetate was heated at 30 °C in fhe presence of a catalytic amount of the organotin dimer deacetylation proceeded quite smoothly to furnish the parent alcohol, in which a variety of acid-labile functional groups remained intact. Acetates of primary alcohols and phenols underwent rapid deacetylation whereas acetates of secondary alcohols reacted only sluggishly. When fhis deacetylation procedure was apphed to acetates derived from tertiary alcohols fhey remained intact, and decomposed under harsher conditions. When nonracemic acetates derived from chiral alcohols and aminoalcohols were treated wifh [tBu2SnOH(Cl)]2 in MeOH, the desired deacetylation proceeded, and no racemization was observed. Exclusive deacetylation of primary alcohols in fhe reaction of peracetates of carbohy-... 

Preparation of cyclic ethers by intramolecular reactions of the primary (29 and 33) and the secondary alcohols (31 and 35) proceeds more easily using CS2CO3 or K3PO4, and binaphthyl-based monophosphine ligands VI-1, VI-9 [9], The five-, six-, and seven-membered cyclic ethers 30, 32, and 34 were prepared from the aryl chloride 31 and bromides 29 and 33. The benzoxazapine 36 was obtained without racemization of chiral alcohol by the cyclization of the optically active bromo alcohol 35. 

Kinetic Resolution of Alcohols. Primary alcohols may be resolved with moderate to good selectivities by Pseudomonas sp. lipase (PSL) using vinyl acetate [186] or acetic anhydride as the acyl dmior (Scheme 3.9). Whereas the selectivities achieved were moderate with alkyl and aiyl substituents, substrate modification via introduction of a bulky sulfur atom in helped considerably. In this way, chiral isoprenoid synthons having a Cs-backlxMie were obtained in >98% enantiomeric excess. 

Here, the use of cesium bases is crucial due to the inherently enhanced nucleo-philicities of the corresponding cesium alkoxides generated in situ from various aliphatic alcohols. Primary and secondary alcohols are easily incorporated into CO2, and then the products, in turn, react with diverse halides, including secondary bromides, which are usually resistant to alkylations due to eliminations. The stereochemical sense is lost to a negligible extent, if at all. Using chiral templates, carbonates are formed efficiently without any elimination or hydrolysis, and little or no racemization is observed [711]. 

This is the first example of a highly enantioselective reaction induced by chirality resulting from deuterium substitution of amino acids. In addition, chirally deuterated primary alcohols [52] and chiral amino acid derivatives with partially deuterated substituent such as monodeuterated methyl group (—CDH2) can induce the chirality in asymmetric autocatalysis [53]. 

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