Asymmetric reduction of aldehydes

There are several ways for achieving asymmetric reduction of aldehydes and ketones. For example, a chiral catalyst or chiral reagent can be used for the enantioselective reduction. 

Chiral reductions are now quite common with these reagents when used either in stoichiometric amounts [CT4, MT6, SCI] or in catalytic amounts in the presence of BH3 THF, catecholborane [G6, GB6, QWl, SK5], or BH3 Me2S as achiral reducing co-reagent [DS6, JM3, N5, S5, SCI, SM6, TA3, TBl, YL4]. The asymmetric reduction of aldehydes, various ketones, a-enones, and a-ynones usually take place with an excellent enantiomeric excess [BB13, CL2, CL6, CR2, CT4, DS5, DK2, GB6, MT6, NNl, PL2, S4, SM6, WM2] (Figure 3.24). The reduction of ketones is carried out between -20°C and r.t., while that of aldehydes requires - 126°C for a good asymmetric induction. 

Metal alkoxides have promising role in catalytic reactions. In this chapter, we briefly review the history, chciracteristics, cuid synthesis routes of metal alkoxide and then discuss some catalytic processes that are performed with them. These processes include polymerization of different olefin oxides and cyclic esters asymmetric reduction of aldehydes and ketones oxidation of sulfides and olefins and a variety of other asymmetric reactions. The rest of the chapter discusses the characteristics of these catalytic systems from different points of view. 

The synthesis of 10 features the SN2 displacement of the allylic acetate with migration of R2 from the ate complex6. Precursors 9 are prepared by the hydroboration of 3-acetoxy-l-alkynes that are available with very high enantiomeric purity via the asymmetric reduction of the corresponding l-alkyn-3-ones, and a substantial degree of asymmetric induction occurs in the conversion of 9 to 10. Best results, based on the enantioselectivity of reactions of 10 with aldehydes, are obtained when R2 is a bulky group such as isopinocampheyl (79 85 % ee)6. The yields of reactions of 10 with aldehydes are 62-76%. 

Reduction of carbonyl groups Terpene and aromatic aldehydes (lOOppm) were reduced by microalgae. In a series of chlorinated benzaldehyde, m - or p-chlorobenzaldehyde reacted faster than the o-derivative. Due to toxicity, the substrate concentrations are difficult to increase. Asymmetric reductions of ketones by microalgae were reported. Thus, aliphatic " and aromatic " ketones were reduced. 

The intermediate enolate or enol ether from the initial reduction of an enone may be alkylated in situ (Eq. 281).455 / -Substituted cyclopentenones may be asymmetrically reduced and alkylated459 (see section on asymmetric reductions of enones). Enolates may also be trapped with an aldehyde in a reductive aldol condensation of an enone with an aldehyde,455 permitting a regioselective aldol condensation to be carried out as shown in Eq. 282.455 This class of reductive aldol condensation reactions can also occur in a cyclic manner (Eq. 283).460... 

Asymmetric reduction of ketones or aldehydes to chiral alcohols has received considerable attention. Methods to accomplish this include catalytic asymmetric hydrogenation, hydrosilylation, enzymatic reduction, reductions with biomimetic model systems, and chirally modified metal hydride and alkyl metal reagents. This chapter will be concerned with chiral aluminum-containing reducing re-... 

Asymmetric reduction of a,/l-unsaturated aldehydes with transition metal catalysts has not yet proven ready for widespread industrial application. One area, namely the chiral reduction of enals to yield chiral alcohols using bakers yeast has been... 

Asymmetric reduction of a,f -acetylenic ketones. This borane can be used to reduce 1-deulerio aldehydes to chiral (S)-l-deulerio primary alcohols in 90% optical yields. It also reduces a,/ -acctylcnic ketones to (R)-propargylic alcohols with enantiomeric purity of 73-100%. The ee value is increased by an increase in the size of the group attached to the carbonyl group. The value is also higher in reductions of terminal ynones. Alcohols of the opposite configuration can be obtained with the reagent prepared from (— )-a-pinene. 

Catalytic asymmetric synthesis of enantiopure diaryl-methanols and -methylamines (important pharmaceutical intermediates) has been reviewed (76 references), focusing on (i) aryl transfers on to aryl-aldehydes and -imines and (ii) asymmetric reductions of diaryl-ketones and -ketoimines.284... 

A review describing the major advances in the field of asymmetric reduction of achiral ketones using borohydrides, exemplified by oxazaborolidines and /9-chlorodiisopino- camphenylborane, has appeared. Use of sodium borohydride in combination with chiral Lewis acids has been discussed.298 The usefulness of sodium triacetoxyboro-hydride in the reductive amination of aldehydes and ketones has been reviewed. The wide scope of the reagent, its diverse and numerous applications, and high tolerance for many functional groups have been discussed.299 The preparation, properties, and synthetic application of lithium aminoborohydrides (LABs) have been reviewed. 

A Et2Zn-(5, S)-linked-BINOL (21) complex has been found suitable for chemos-elective enolate formation from a hydroxy ketone in the presence of isomerizable aliphatic iV-diphenylphosphinoylimines.103 The reaction proceeded smoothly and /9- alkyl-yS-amino-a-hydroxy ketones were obtained in good yield and high enantioselectivity (up to 99% ee). A titanium complex derived from 3-(3,5-diphenylphenyl)-BINOL (22) has exhibited an enhanced catalytic activity in the asymmetric alkylation of aldehydes, allowing the reduction of the catalyst amount to less than 1 mol% without deterioration in enantioselectivity.104... 

The enzyme catalyzing the asymmetric reduction of ethyl 2 -ketopan-tothenate was isolated from Candida macedoniensis [110] (see Tables 4 and 5). The enzyme is NADPH-dependent and shows broad substrate specificity not only conjugated polyketones, but also aromatic aldehydes and 4-haloaceto-acetate esters are reduced. Thus, it has been suggested that it could be a kind of... 

Aldehyde reductase of S. salmonicolor can catalyze the asymmetric reduction of 4-haloacetoacetate esters to the corresponding (-R)-alcohols, which are promising chiral building blocks for the preparation of a variety of optically active compounds such as L-carnitine [119] (Fig. 9). 

In 2005, the groups of List and McMillan simultaneously described excellent results in the asymmetric reduction of a,/ -unsaturated aldehydes with a prochiral center in the ft position [14, 15]. (For experimental details see Chapters 14.22.1 and 14.22.2). In both cases the catalyst used was a chiral imidazolidinone (6 or 8), and some representative examples are listed in Tables 11.1 and 11.2. The reactions were run at 10-20 mol% of catalyst, at moderate temperature (13 °C or 4 °C) over several hours. The hydride source (Hantzsch ester) was utilized in stoichiometric quantities, and the chemical yields and enantiomeric excesses proved to be... 

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