Catalysts for asymmetric reduction

As with hydrogenation, hydrogen transfer of imines is a poorly developed field.126-130 However, recent arene-Ru11 systems bearing chiral 1,2-diamine co-ligands have been found to be excellent catalysts for asymmetric reduction of imines with formic acid as donor.31,131-134... 

Use of ruthenium(III) chloride with poly-L-methylethylenimine is said to give a homogeneous catalyst for asymmetric reduction of the keto... 

The later sections of the book deal with the actual laboratory use of catalysts for asymmetric reduction and oxidation reactions. Most of the protocols describe non-natural catalysts principally because many of the corresponding biological procedures were featured in the sister volume Preparative Biotransformations. As in this earlier book, we have spelt out the procedures in great detail, giving where necessary, helpful tips and, where appropriate, clear warnings of toxicity, fire hazards, etc. 

A chiral lanthanoid complex, which was prepared similarly to La-(/ )-17,7 23 is an effective catalyst for asymmetric reduction of ketones.102 With 10 mol % of the catalyst, borane reduction of ketones proceeds very smoothly to give alcohols in up to 62% ee (Figure 48). 

Redox reactions. With Pdl2 complexed to 3 kinetic resolution of secondary henzyhc and allylic alcohols can be carried out via enantioselective oxidation (O2, CS2CO3, PhMe, 80°). The acetoxydiiodo-Rh carbene complex of 3 is a catalyst for asymmetric reduction of aroylacetic esters with Ph2SiH2- ... 

The versatility of the Meyers reaction for the construction of the dibenzocyclooctadiene backbone is amply documented (Fig. 8.2). In particular, lignans (-)-interiotherin A (17) [21], (-)-schizandrin (18), (-)-isoschizandrin (19) [22], and (-)-gomisin E (20) [21] were prepared by this method. The synthetic utility of the Meyers reaction to create the axially chiral biaryl skeletal framework was further displayed by the atroposelective syntheses of natural naphthylisoquinoline alkaloids including (-)-O-methylancistrocladine (21) [23] and (-)-0-methylhamatine (22) [24], among others [25, 26], and by the synthesis of enantiomericaUy pure C -symmetric biphenyl ligand 23 and binaphthyl porphyrin 24 (Fig. 8.3), which have been used as intermediates for the preparation of chiral catalysts for asymmetric reduction and epoxidation [27, 28]. 

Asymmetric reduction of prochiral ketones is one of most efficient method of the introduction of chirality in the synthesis of non-racemic biologically active compounds. Derived from chiral (S)-diphenyl prolinole the amino borate ester 1 has been prepared, fully characterized and used as highly effective catalyst for asymmetric reduction of ketons with borane. The optically pure alcohols 3 have been prepared using only 1 mol % of catalyst 1 in enantioselectivity up to 97%. 

Figure 15.5 Formamides and related catalysts for asymmetric reduction of ketimines.

Another possibility for asymmetric reduction is the use of chiral complex hydrides derived from LiAlH. and chiral alcohols, e.g. N-methylephedrine (I. Jacquet, 1974), or 1,4-bis(dimethylamino)butanediol (D. Seebach, 1974). But stereoselectivities are mostly below 50%. At the present time attempts to form chiral alcohols from ketones are less successful than the asymmetric reduction of C = C double bonds via hydroboration or hydrogenation with Wilkinson type catalysts (G. Zweifel, 1963 H.B. Kagan, 1978 see p. 102f.). 

In summary, ketoreductases have emerged as valuable catalysts for asymmetric ketone reductions and are preparing to enter the mainstream of synthetic chemistry of chiral alcohols. These biocatalysts are used in three forms wild-type whole-cell microorganism, recombinant... 

In order to show the versatility of the method Davis extended the concept to other hydrophilic liquids such as ethylene glycol and glycerol [70], The reactions then take place at the hydrophilic-hydrophobic liquid interface. In this specific example the supported-phase concept was used for asymmetric reduction using a ruthenium catalyst. 

Carbonyl groups are not reduced with classical Wilkinson catalysts. However, some cationic rhodium complexes show catalytic activity 52K There are only a few examples of asymmetric hydrogenation of ketones. Addition of base to a neutral rhodium complex is also a way to produce a catalyst for ketone reduction 44). Acetophenone... 

Related catalysts for asymmetric borane reduction of ketones are open chain and cyclic phosphoric amides, in the oxidation state +3 or +5 (Scheme 11.3) [10, 11]. Early examples are the phosphonamides and phosphinamides 5a and 5b of Wills et al. [12] and the oxazaphospholidine-borane complex 6a of Buono et al. [13]. In the presence of 2-10 mol% catalysts 5a,b, co-chloroacetophenone was reduced by BH3 SMe2 with 35-46% ee [12]. For catalyst 6a a remarkable 92% ee was reported for the catalytic reduction of methyl iso-butyl ketone and 75% ee for acetophenone... 

A new type of lanthanoid complex, prepared from BINOL and SmCl3, served as an asymmetric catalyst for MPV reduction of aryl methyl ketones in the presence of molecular sieves. Moderate enantioselectivity was obtained.101... 

The organocatalytic enantioselective reduction of C=C, C=0, and C=N double bonds is a relatively young area for which many new and exciting developments can be expected in the near future. Hantzsch esters are useful organic hydrides, and a recent review has summarized the results obtained to date in organocataly-sis [27]. The case of silicon hydrides is convenient for imine or ketone reductions, as a chiral base can act as an organic catalyst. The asymmetric reductions of ketones catalyzed by oxazaborolidines and pioneered by Itsuno [28] and Corey [29] could not be included in this chapter. 

Rh(P2) 22+ dimers. The new [Rh(P2)(P)2]+ complexes can be isolated as their PFg- complexes. These Rh(I) complexes are air-stable in the solid state and serve as extremely active and selective (1,2- vs. 1,4-hydrosilation) asymmetric hydrosilation catalysts for the reduction of ketones with disubstituted silanes. 

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