In asymmetric reduction

Utilizing the Zincke reaction of salts such as 112 (Scheme 8.4.38), Binay et al. prepared 4-substituted-3-oxazolyl dihydropyridines as NADH models for use in asymmetric reductions. They found that high purity of the Zincke salts was required for efficient reaction with R-(+)-l-phenylethyl amine, for example. As shown in that case (Scheme 8.4.38), chiral A-substituents could be introduced, and 1,4-reduction produced the NADH analogs (e.g. 114). 

Nakamura, K., Yamanaka, R., Matsuda, T. and Harada, T. (2003) Recent developments in asymmetric reduction of ketones with biocatalysts. Tetrahedron Asymmetry, 14 (18), 2659—2681. 

Chiral diazaborolidines catalysts in asymmetric reductions have been less described than the corresponding oxaza-borolidines. Although not isolated, the formation of compound 47 has been characterized by nB NMR spectroscopy with the detection of a signal at 24 ppm (from BF3.Et20 as an external standard) <2000TA4329>. 

The stannepins which encompass the 2,2 -positions of 1,1 -binaphthyl are interesting because, in their enantiomeric forms, they can bring about stereoselective reactions. Scheme 14 shows the synthesis of the methyltin hydride, which has been used in asymmetric reduction,172 and of the dimethyltin compound, which, via lithiation, can act as the precursor for further derivatives such as the silepins.327... 

Despite the uncertainties of mechanism and of the identity of reactive species, attempts have been made to analyze stereochemical control in asymmetric reductions in terms of a model of the transition state in which steric or other interactions can be assessed. These models could prove useful in suggesting modifications for improving the design of selective reducing agents or for predictive purposes. However, it should be kept in mind that there are only two possible outcomes in the direction of asymmetric induction at a prochiral unit undergoing reaction, and confidence in the predictive usefulness of a given model can only be obtained after a considerable number of examples have been examined. 

Scheme 4.33 PEC-supported BINAP-ligand in asymmetric reductions of electron def-ficient alkenes.

The paramount significance of chiral amines in pharmaceutical and agrochemical substances drives the development of efficient catalytic asymmetric methods for their formation. In contrast to the high enantioselectivities observed in asymmetric reduction of both alkenes and ketones, only limited success has been achieved in the enantiose-lective hydrogenation of imines [118]. Currently, there are few efficient chiral catalytic systems available for the asymmetric hydrogenation of imines. 

Optical yields are always low in asymmetric reduction of simple olefins where no polar groups are close to the double bond 41a,51). 

As an extension of these studies on the use of sulfoximines in asymmetric reductions, BlNOL-derived phosphino sulfoximines of the 105 type were tested in both rhodium-catalyzed hydrogenations (yielding optically active diesters 104 or amino acid derivatives Scheme 2.1.1.35) and palladium-catalyzed allylic alkylations (not shown) in collaboration with Reetz and Gais [81, 82]. Here, enantioselectivities of up to >99 and 66% ee, respectively, were achieved. 

Dimethylborolane has been shown to be effective in asymmetric reduction of ketones (Imai, T. Tamura, T. Yamamuro, A. Sato, T. Wollmann, T. A. Kennedy, R. M. Masamune, S., J. Am. Chem. Soc., 1986, 108, 7402-7404). Using the frontier orbitals of a borolane and a ketone, show the probable course of the initial interaction between the two. 

Asymmetric catalysis allows chemicals to be manufactured in their enantiomer-ically pure form and reduces derivatisation and multiple purification steps that would otherwise be required. The 2001 Nobel Prize was awarded for two of the most important asymmetric reactions hydrogenations and oxidations. A variety of ligands suitable for asymmetric reductions are available commercially including BINAP, Figure 3.16. A BINAP Rh complex is used in the commercial production of 1-menthol to enantioselectively hydrogenate an alkene bond (Lancaster, 2002). Ru BINAP complexes can be used in asymmetric reductions of carbonyl groups (Noyori, 2005 Noyori and Hashiguchi, 1997). 

In general, structural variations to the backbone of the Chirald ligand have not led to the development of more selective or reliable LAH complexes for use in asymmetric reductions. Other complexes of amino alcohols with LAH have been studied for their ability to achieve enantioselective reduction of prochiral ketones. However, in most cases the selectivities observed have been moderate. The complex of LAH with the amino alcohol (IS) reduces some enones, such as cyclohexenone and cyclopentenone, to the corresponding (5)-alcohols in high optical purities (100% and 82% ee, respectively). ... 

Ramachandran, P. V., Brown, H. C. Recent Advances in Asymmetric Reductions with B-Chlorodiisopinocampheyl borane. Am. Chem. Soc. Monograph 641, Washington, DC, 1996. 

Rogic, M. M. Conformational Analysis and the Transition State in Asymmetric Reductions with Boranes Based on (+)-a-Pinene. 1. Benzaldehyde Reduction with Alpine Borane and Other B-Alkyl-9-borabicyclo[3.3.1]nonanes. ASemiempirical Study. J. Org. Chem. 1996, 61, 1341-1346. 

Rogic, M. M., Ramachandran, P. V., Zinnen, H., Brown, L. D., Zheng, M. The origins of stereoselectivity in asymmetric reductions with boranes based on (+)-a-pinene. II. The geometries of competing transition-states and the nature of the reaction. A semiempirical study. 

Phosphorus-containing Ring Systems. - A range of new chiral oxazaphospholidine oxides 266 and 267 have been synthesised and used as catalysts in asymmetric reductions of ketones with diborane. Mannich-type cyclisation reactions of 5-amino-3-benzylthio-4-cyano(ethoxycarbonyl)pyrazoles with dichlorophenylphosphine and aromatic aldehydes in the presence of cation exchange resin have been used to prepare a number of 6-oxo-6-phospha-4,5,6-trihydroimidazolo[l,2-b]pyrazoles, e.g. 268. Some of these compounds have herbicidal activity and this report is typical of a number of similar ones in the Chinese literature. A number of metallocycles, e.g. 269, have been reported as products from reactions of transient zirconocene-benzyne intermediates with phosphaimines followed by sulfuration or selenation. ... 

Various sodium aminoaluminohydrides have been proposed for selective reduction of esters and aromatic nitriles to the corresponding aldehydes [CK3, CK5, CJl, YA2J. Chiral alkoxy- and aminoaluminohydrides have been used in asymmetric reductions of ketones and imines, and these will be described in the corresponding chapters (Sections 3.2.3 and 3.3.1). 

Chiral Li alkylborohydrides have been used in asymmetric reductions (Section 3.2.3) [BJl, BR4]. 

Some amino alcohols react with borane to generate oxazaborolidines, which have been mainly used in asymmetric reduction of ketones (Section 3.2.3) and imines (Section 3.3.1) [NNl, S3]. In addition, they can also perform some chemoselective reductions [IWl]. 

Although some promising results have been obtained in asymmetric reduction of... 

Steric bulkiness of substituents in ketones (25), for example, makes it possible to differentiate two pairs of lone-pair electrons (a or b in 25) on carbonyl oxygen for coordinating with the Lewis acidic center of boron in oxazaborolidine (28). The complex (29) formed from 28 with catecholborane binds ketone (32) stereospecifically by using the lone-pair electrons at the less hindered side so as to direct the smaller substituent Rs toward the bulky N-tert-butyl group. The intramolecular hydride transfers to the favorably coordinated carbonyl group as shown in 30, Scheme 1.82, results in asymmetric reduction of ketones. Reduction of trifluoromethyl and methyl ketones (25) (R = CF3 or CH3) by this system afforded the corresponding alcohols (26 or 27) with an opposite stereochemistry (Scheme 1.82). 

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