Synthesis chiral alcohol

The above sequence was demonstrated on racemic onti-mercaptol alcohol 14 as well on a small amount of optically pure 14 (separated by chiral HPLC separation) and the chiral centers of 14 were completely retained, as expected (Scheme 5.6) [8]. With proof of concept for the ring formation strategy, some efforts were put into developing a chiral synthesis of 14, as shown in Scheme 5.7. 

Selective vinylation of aldehydes lags far behind allylation as a synthetic method despite importance of chiral allylic alcohols in synthesis. Vinylmetal species are generally much less nucleophilic that their allyl counterparts, and some vinylmetallic species, such as organotitanium, run into stability issues not encountered in alkylmetals.92... 

Kissel, Ramsden, and other researchers at Pfizer and Chirotech jointly published a novel chiral synthesis of pregabalin (2) in 2003 based on asymmetric hydrogenation (Burk et al., 2001, 2003). Their synthesis started with the condensation of isobutyralde-hyde with acrylonitrile under Baylis-Hillman conditions to give allylic alcohol 65. This alcohol was activated as the carbonate 66 and subjected to palladium-catalyzed car-bonylation conditions to give cyanoester 67. The ester 67 was hydrolyzed and converted to... 

In a similar manner, intramolecular cyclization of the O-stannyl ketyl derivatives 201 and 206, generated from the oxazolyl aldehydes 200 and 205, provides a facile method for the chiral synthesis of 3-hydroxy-2-(hydroxymethyl)-5-substimted-pyrrolidines 202 and 203 and the piperidine analogues 207 and 208 that can be successfully transformed into naturally occurring amino alcohols, (+)-bulgecinine 204 and (—)-desoxoprosopinine 209, respectively (Fig. 

Enantioselective Diels-Alder reaction,3 The reaction of the chiral acrylate ester 1 with butadiene catalyzed with this Lewis acid followed by hydride reduction gives the alcohol 2 in 70% chemical yield and 86-91% ee. A1C13 and SnCl4 are inferior in terms of either the chemical or optical yield. The product (2) was used for a chiral synthesis of (R)-(- )-sarkomycin (4). 

A chiral synthesis of stegobinone (SSS) is based on the cleavage of (25,35)-2,3-epoxybutane with lithium diphenylcuprate, which occurs with complete inversion. The resulting chiral alcohol is converted into the mixed anhydride, which is used to acylate the... 

Ferrocenyl amido complexes, with Zr(IV), 4, 773 Ferrocenyl amino alcohols, synthesis, 6, 202 Ferrocenylated ODN, characteristics, 1, 909—910 Ferrocenyl diols, chiral, synthesis, 6, 204 Ferrocenyldiphenylphosphines, preparation, 6, 202 Ferrocenylimines mercuration, 2, 433 into platinacycles, 8, 511... 

Nakamura, K. Matsuda, T. Harada, T. Chiral synthesis of secondary alcohols using Geotrichum candidum. Chirality, 2002, 14 703-708. 

Pirrung, M.C. and Shuey, S.W. (1994) Photoremovable protecting groups for phosphorylation of chiral alcohols. Asymmetric synthesis of phosphotriesters of (—)-3, 5 -dimethoxybenzoin. Journal of Organic Chemistry, 59, 3890-3897. 

Lipase-catalysed transesterification of the racemic alcohol 67 has been used effectively to produce (5)-(+)-67 (LipaseQL, 0-5 °C, 4h 47% yield >99% ee), which was then converted to a chiral precursor required for the synthesis of the non-peptide vasopressin Vi receptor agonist, OPC-51803 [02H635]. The chiral synthesis of a 1-benzazepine-based antagonist (OPC-41061) at this receptor has also been described [02H123],... 

Pig Liver Esterase (PLE). This is the more used car-boxylesterase (carboxylic-ester hydrolase, EC 3.1.1.1, CAS 9016-18-6) which physiologically catalyzes the hydrolysis of carboxylic acid esters to the free acid anion and alcohol. PLE is a serine hydrolase which has been widely used for the preparation of chiral synthons and these applications have been fully reviewed. An active-site model for interpreting and predicting the specificity of the enzyme has been published. In the pioneering studies of the enzyme applications field, PLE was used for the chiral synthesis of mevalonolactone. Prochiral 3-substituted glutaric acid diesters... 

Faller, J. W., Sams, D. W. I., Liu, X. Catalytic Asymmetric Synthesis of Homoallylic Alcohols Chiral Amplification and Chiral Poisoning in a Titanium/BINOL Catalyst System. J. Am. Chem. Soc. 1996,118, 1217-1218. 

To synthesize a large amount of enantiopure chiral MaNP acid (3), the facile synthesis and enantioresolution of racemic acid 3 were carried out as shown in Fig. 9.9. In general, for enantioresolution of carboxylic acids, chiral synthetic amines or alkaloids have been used. However, we have adopted the following novel strategy using chiral alcohols chiral alcohols are condensed with racemic acid 3 and the diastereomeric esters formed are separated by HPLC on silica gel. 

Rama Rao et al. [30] have recently reported a chiral synthesis of S(-)-tetrami-sole starting from the optically active alcohol (44), which was prepared with 97% ee by reducing phenacyl chloride (42) with oxazaborolidines (43) in the presence of BH3. Further reactions leading to S(-)-tetramisole are shown in scheme 8. 

Workers at Lilly have reported the synthesis of 8,9-LTA3 (51), 8,9-LTC3 (52a), and 8,9-LTD3 (52b),leukotrienes that are reported to be produced from dihomo-y-linolenic acid in ionophore-stimulated murine mastocytoma cells. The natural stereochemistry was assumed to be (85,9/f,10,12 ,14Z) by analogy with arachidonic acid metabolism in the same cell system. The chiral synthesis was achieved (93% ee) via Sharpless epoxidation of an appropriate allylic alcohol (53) (Scheme 5.17). 

The full paper describing Mori s synthesis of lineatin (296) (Vol. 4, p. 489, Ref. 263) has been published. After converting the lactone 329 to ( )-lineatin using a [2 + 2] cycloaddition, Slessor et al. followed another route from the same lactone 329, which is readily available by the Lewis acid-catalyzed addition of ketene to mesityl oxide. The route is shown in Scheme 25. In this scheme, the mixture arising from the carbene addition is not separated because, at the stage of the epoxide formation, only the major (desired) isomer 330 was isolated, the other being thermally unstable. The exo alcohols obtained in small amounts after the borohydride reduction (step h) were not isolated. To obtain the natural isomer of lineatin [( + )-(l/ ,4S,5/ ,7R)-296] the alcohol 331 was resolved with (—)-(r)-l-(l-nephthyl)ethyl isocyanate/triethylamine. The first stereospecific chiral synthesis of (+)-lineatin (296) started from D-ribonolactone (332), and is illustrated (in somewhat abbreviated form) in Scheme 26 it proceeded in 2.7% overall yield. °... 

Amines -> alcohols. A synthesis of secondary alcohols in chiral form from A-Boc secondary amines involves lithiation with the BuLi - (-)-sparteine complex, quenching with RgB, and decomposing the reaction mixture with NaOH-HgOg. ... 

Hanson RL, Goldberg S, Goswami A, et al. Purification and cloning of a ketoreductase used for the preparation of chiral alcohols. Advanced Synthesis and Catalysis 347(7-1-8), 1073, 2004. 

Chiral Redox Chemistry - Nicotinamide cofactor dependent oxldoreductases have been applied in chiral synthesis. Enantloselectlvlty is often only moderate, but in certain cases excellent results have been obtained. Horse liver alcohol dehydrogenase (HLADH) is the most widely explored enzyme for these purposes with most of the work in this area having been... 

Jadhav PK, Bhat KS, Perumal PT, Brown HC (1986) Chiral synthesis via organoboranes. 6. Asymmetric allylboration via chiral allyldialkylboranes. Synthesis of homoallylic alcohols with exceptionally high enantiomeric excess. J Org Chem 51 432-439... 

In 1980, K. B. Sharpless (then at the Massachusetts Institute of Technology, presently at The Scripps Research Institute) and co-workers reported a method that has since become one of the most valuable tools for chiral synthesis. The Sharpless asymmetric epoxidation is a method for converting allylic alcohols (Section 11.1) to chiral epoxy alcohols with very high enan-tioselectivity (i.e., with preference for one enantiomer rather than formation of a racemic mixture). In recognition of this and other work in asymmetric oxidation methods (see Section 8.16A), Sharpless received half of the 2001 Nobel Prize in Chemistry (the other half was awarded to W. S. Knowles and R. Noyori see Section 7.14). The Sharpless asymmetric epoxidation involves treating the allylic alcohol with tert-butyl hydroperoxide, titanium(IV) tetraisopropoxide [Ti(0—/-POJ, and a specific stereoisomer of a tartrate ester. (The tartrate stereoisomer that is chosen depends on the specific enantiomer of the epoxide desired). The following is an example ... 

Boronic esters (3) can be homologated to a-chloroboronic esters (4) (Scheme 2) replacement of the chlorine atom by carbon nucleophiles, such as Grignard reagents, and oxidation of the carbon-boron bond gives a new route to alcohols/ If the sequence is performed with (+)- or (-)-pinanediol boronic esters it can be made into a directed chiral synthesis of alcohols, as illustrated in Scheme 3 from phenyl boronic acid the homologation steps were found to occur with diastereoselectivities in excess of 90%, the chlorine replacement proceeds with inversion, and the oxidative step with retention of configuration. 

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