Enantioselectivity reduction, of carbonyl compounds

Ernst, M., Kaup, B., Mueller, M. et al. (2005) Enantioselective reduction of carbonyl compounds by whole-cell biotransformation, combining a formate dehydrogenase and a (R)-specihc alcohol dehydrogenase. Applied Microbiology and Biotechnology, 66 (6), 629-634. 

Figure 3.21 shows reaction equations and the energy relationships of the hydrobo-ration of enantiomerically pure a-pinene with 9-BBN. The reagent approaches only the side of the C=C double bond that lies opposite the isopropylidene bridge. The addition is thus completely diastereoselective. Moreover, the trialkylborane obtained is a pure enantiomer. It is used as Alpine-Borane for the enantioselective reduction of carbonyl compounds (Section 8.4). 

Chiral modification is not limited to boronate and aluminate complexes. Boranes or alanes are partially decomposed with protic substances such as chiral amines, alcohols or amino alcohols to form useful reagents for enantioselective reduction of carbonyl compounds. For example, reduction of acetophenone with borane modified with the amines (65) to (67) gives (5)-l-phenylethyl alcohol with 3.5-20%... 

Nevalainen, V. Quantum chemical modeling of chiral catalysis. On the mechanism of catalytic enantioselective reduction of carbonyl compounds by chiral oxazaborolidines. Tetrahedron Asymmetry 1991,2, 63-74. 

S)-l-Benzyloxycarbonyl-2-[hydroxy(diphenyl)methyl]pyrrolidine [(S)-25] was used as an auxiliary in the enantioselective reduction of carbonyl compounds to secondary alcohols (Section D.2.3.2.) it is prepared analogously to the a,a-dimethyl derivative25. The A -methyl derivative (S)-26 (DPMPM) is among the most selective catalysts for the addition of zinc alkyls to carbonyl compounds (Section D.1.3.1.4.). 

Corey, E.J. Helal, C.J. (1998) Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method. Angewandte Chemie International Edition, 37, 1986-2012. 

The control of enantioselectivity in the reduction of carbonyl compounds provides an opportunity for obtaining the product alcohols in an enantiomerically enriched form. For transfer hydrogenation, such reactions have been dominated by the use of enantiomerically pure ruthenium complexes [33, 34], although Pfaltz and coworkers had shown by 1991 that high levels of enantioselectivity could be obtained using iridium(I) bis-oxazoline complexes [35]. 

Enzymatic reduction of carbonyl compounds and enzymatic enantioselective transformation of racemic or meso alcohols (25,43.) are two methodologies that have proven to be beneficial in the preparation of optically active hydroxyl compounds, key chiral building blocks used in carbohydrate and natural product syntheses (44-45. Our interest in this area is to develop enzymatic routes to optically active glycerol and furan derivatives, and hydroxyaldehydes. 

Corey EJ, Helal CJ (1998) Reduction of carbonyl compounds with chiral oxazaborolidine catalysts a new paradigm for enantioselective catalysis and a powerful new synthetic method. Angew Chem Int Ed 37 1986-2012... 

The reduction of carbonyl compounds with LAH complexes of a number of chiral diols derived from carbohydrates and terpenes has been studied. In general, the enantioselectivities observed with such reagents have been low to moderate. Acetophenone, which is the model substrate in many of these reduction studies, is reduced by a complex of LAH and the glucose-derived diol (2) in about 71% ee under optimized conditions. 

Tartarie acid [(/ ,/ )-20J is one of the most inexpensive chiral compounds available even the (.S. .S )-enantiomer, which does not occur so frequently in nature, is comparatively inexpensive, so there is no need for laboratory synthesis. Most diesters of both enantiomers are also inexpensive, at least for the C, - C3 alcohols. Tartaric acid itself has been used for the chiral modification of the surface of Raney nickel, which permits highly enantioselective reduction of carbonyl groups, e.g., of oxo esters, to the secondary alcohols (Section D.2.3.I.). The zinc salt of tartaric acid has been used for the asymmetric ring opening of epoxides by thiolates (Section C.). The diesters, e.g., 21-25, are conveniently obtained by acid-catalyzed esterification28-31, a method applicable to almost all alcohols as a typical example, dicyclohexyl (f ,tf)-tartrate is given32. 

E. J. Corey, C. J. Helal, Angew. Chem. 1998, 110, 2092 Angew. Chem. Int. Ed. 1998, 37, 1986 (Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method.), S. Itsuno, in Organic Reactions , Ed. L. A. Paquette, John Wiley Sons, New York, 1998, Vol. 52, pp. 395-576 (Enantioselective Reduction of Ketones). 

Although highly eflfective asymmetric reduction of carbonyl compounds has been extensively investigated, enantioselective reduetion of imine derivatives to amines has been less studied, mainly in homogeneous supported catalysis [66],... 

ABSTRACT. Pentacoordinate organosilicon species behave as Lewis acid as well as nucleophile. This unique character provides several interesting applications in selective reactions useful for organic synthesis. Accordingly, new reduction of carbonyl compounds with pentacoordinate hydridosilicates, new regio- and enantioselective allylation of aldehydes with pentacoordinate allylsilanes, and the new cleavage reaction of C-Si bonds are discussed. In these reactions, it is demonstrated that unique characters of pentacoordinate silicon species as a Lewis acid play an important role. 

Other microorganisms have also been used for the asymmetric reduction of carbonyl compounds. Simple ahphatic ketones as well as aromatic ketones can be reduced with very high enantioselectivity by using biocatalysts. For example, aliphatic ketones such as... 

The hydrogenation of ketones with O or N functions in the a- or / -position is accomplished by several rhodium compounds [46 a, b, e, g, i, j, m, 56], Many of these examples have been applied in the synthesis of biologically active chiral products [59]. One of the first examples was the asymmetric synthesis of pantothenic acid, a member of the B complex vitamins and an important constituent of coenzyme A. Ojima et al. first described this synthesis in 1978, the most significant step being the enantioselective reduction of a cyclic a-keto ester, dihydro-4,4-dimethyl-2,3-furandione, to D-(-)-pantoyl lactone. A rhodium complex derived from [RhCl(COD)]2 and the chiral pyrrolidino diphosphine, (2S,4S)-N-tert-butoxy-carbonyl-4-diphenylphosphino-2-diphenylphosphinomethyl-pyrrolidine ((S, S) -... 

One approach to enantioselective reduction of prochiral carbonyl compounds is to utilize chiral ligand-modified metal hydride reagents. In these reagents, the number of reactive hydride species is minimized in order to get high chemo-selectivity. Enantiofacial differentiation is due to the introduced chiral ligand. 

Since the electroreduction of ketones shown in Scheme 29 has been well established [1-3, 12, 62-65], one more recent interest in the electroreduction of carbonyl compounds is focused on the stereo-selective reduction of ketones. For example, the diastereo-selective cathodic coupling of aromatic ketones has been reported. In the presence of a chiral-supporting electrolyte, a low degree of enantioselectivity has been found [66] (Scheme 30). 

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

Baker s yeast reduction of organic compounds, especially carbonyl compounds, is an extremely useful method of obtaining chiral products255-257. Recently, much effort has been expended to improve the ee obtained in this process. In one very useful example, l-acetoxy-2-alkanones have been reduced enantioselectively into (5 )-l-acetoxy-2-alkanols in 60-90% yields and with 95-99% ee258. The reaction readily occurs in a variety of solvents, both aqueous and nonaqueous. The reduction is fairly selective and so may be brought about in the presence of a-amide, ether, ester and other acid functional groups, in reasonable yields and with excellent ee (equation 65)259 -261. Thus, in the synthesis of the C-13 side chain of taxol, the key step was the reduction of a w-ketoester to the corresponding alcohol in 72% overall yield (equation 66)262. 

The hydrosilylation of carbonyl compounds with polymethylhydrosiloxane (PMHS) or other alkoxysilanes can be catalyzed by TBAF, at high efficiency [9]. The asymmetric version of this process has been developed by Lawrence and coworkers using chiral ammonium fluoride 7c prepared via the method of Shioiri [10]. The reduction of acetophenone was performed with trimethoxysilane (1.5 equiv.) and 7c (10 mol%) in THF at room temperature, yielding phenethyl alcohol quantitatively with 51% ee (R) (Scheme 4.6). A slightly higher enantioselectivity was observed in the reduction of propiophenone. When tris(trimethylsiloxy)silane was used as a hydride source, the enantioselectivity was increased, though a pro-... 

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