Enantioselective reactions carbonyl reductions

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]. 

Asymmetric transfer hydrogenation of imines catalyzed by chiral arene-Ru complexes achieves high enantioselectivity (Figure 1.34). Formic acid in aprotic dipolar solvent should be used as a hydride source. The reaction proceeds through the metal-ligand bifunctional mechanism as shown in the carbonyl reduction (Figure 1.24). 

One enantiomer can be formed selectively from the reduction of a carbonyl group, provided a cbiral reducing ent is used. This strategy is identical to that employed in the Sharpless asymmetric epoxidation reaction (Section 12.15). A reduction that forms one enantiomer predominantly or exclusively is an enantioselective or asymmetric reduction. 

This reaction is completely enantioselective. For example, reduction of pyruvic acid with NADH catalyzed by lactate dehydrogenase affords a single enantiomer of lactic acid with the S configuration. NADH reduces a variety of different carbonyl compounds in biological systems. The configuration of the product (/ or S) depends on the enzyme used to catalyze the process. 

Control of enantioselectivity will be discussed in the corresponding sections on carbonyl reduction (Chapter 4) alkene hydrogenation, epoxidation, and dihydroxylation (Chapter 5) aldol condensation (Chapter 6) allylation and crotylation (Chapter 7) Claisen rearrangement (Chapter 8) and the Diels-Alder reaction (Chapter 9). 

Earlier in 2007, the same authors reported the first example of intermo-lecular enantioselective nickel-catalysed reductive coupling of 1,3-dienes with carbonyl compounds. As shown in Scheme 3.28, the reaction of... 

A-Formylamines can be prepared by the Leuckart reaction, a reductive amination of carbonyl compounds by reaction with formamide and formic acid. Evidence for an unprecedented intramolecular transamidation in the mechanism of enantioselective Leuckart reaction of 2-norbornanone with a (l-norbornyl)acetamide is presented. ... 

The enantioselective reduction of alkyl 3-oxobutanoates by carbonyl reductase (SI) from C. magnoliae was also performed in organic-aqueous two-phase reaction system (Figure 8.15) [llc,d]. 

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

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