Enantioselective borane reduction

Another soluble polymer-enlarged catalyst was synthesized and tested by Wandrey et a/.[57] The catalyst was prepared by a coupling of an oxazaborolidine via a hydrosilylation reaction to a methyl hydrosiloxane-dimethylsiloxane copolymer (Figure 4.40). The catalyst was used in the enantioselective borane reduction of ketones. 

Evans et al.106 report an asymmetric transfer hydrogenation of ketones using samarium(III) complex (108) as the catalyst at ambient temperature in 2-propanol. The products showed ee comparable with those obtained through enantioselective borane reduction (Scheme 6-48). 

Enantioselective reduction of ketones.1 The ability of diborane in combination with the vic-amino alcohol (S)-2-amino-3-methyl-l,l-diphenyl-l-butanol (12, 31) to effect enantioselective reduction of alkyl aryl ketones involves formation of an intermediate chiral oxazaborolidine, which can be isolated and used as a catalyst for enantioselective borane reductions (equation I). 

Enantioselective borane reduction of prochiral ketones catalysed by chiral oxabor-olidines is of considerable synthetic utility, but the catalytic cycle has to compete with direct borane reduction of the ketone. Accordingly, precise kinetic data on the latter would help optimize conditions for the former. Such a study has been... 

Enantioselective borane reduction of ketones catalyzed by chiral oxazaborolidines. 

Use of thiaprolinol amino alcohols as ligands for enantioselective borane reduction of ketones111 and of a fluorotitanium-TADDOLate to catalyse reduction of benzaldehyde87c has been described above under Organometallics and Allylation Reactions, respectively. 

A polymer-bound oxazaborolidine catalyst enantioselective borane reductions of ketones, Tetrahedron Asymm. 1995, 6, 2755-2766. 

Researchers at Sepracor later disclosed the use of a new class of chiral oxazaborolidines derived from r/. v-aminoindanol in the enantioselective borane reduction of a-haloketones.6,7 The 5-hydrogen oxazaborolidine ligand 10 was prepared in situ from d,v-aminoindanol 1 and BH3 THF.8 Stock solutions of 5-methyl oxazaborolidine 11-16 were obtained by reaction of the corresponding N-alkyl aminoindanol with trimethyl boroxine.6,7 5-Methyl catalyst 11 was found to be more selective (94% ee at 0°C) than the 5-hydrogen catalyst 10 (89% ee at 0°C), and enantioselectivities with 11 increased at lower temperatures (96% ee at -20°C). The catalyst structure was modified by introduction of A-a I kyI substituents. As a general trend, reactivities and selectivities decreased as the steric bulk or the chelating ability of the A -alkyl substituent increased (Scheme 17.4). 

Corey, E. J., Bakshi, R. K., Shibata, S. Highly enantioselective borane reduction of ketones catalyzed by chiral oxazaborolidines. 

Chiral organophosphorus compounds have been found to act as catalysts in numerous enan-tioselective reactions. This review highlights recent developments in this area and more precisely in the kinetic resolution of secondary alcohols, the enantioselective borane reduction of ketones, and in the asymmetric C-C bond formation with the introduction of asymmetric two-center catalysts. 

Use of Chiral Phosphine-Borane Complexes in the Enantioselective Borane Reduction of Ketones. 84... 

Table 3. Enantioselective borane reduction of different ketones ...

More recently, Muller et al. [31] and Chan et al. [32] have independently mentioned the highly enantioselective borane reduction of acetophenone in presence of a catalytic amount of organophosphorus borane complexes 22 and 23 is-... 

In 1996, the enantioselective borane reduction of imines catalyzed by an oxazaphospholidine-borane complex in refluxing toluene has been described. Thus, optically active amines have been obtained with enantioselectivities up to 63% [33]. 

On the basis of such hypothesis, the synthesis and use of new phosphine oxides from (S)-prolinol has been realized. Thus, enantioselective borane reduction of chloroacetophenone at 60 °C in THF in presence of 1 mol% of 24 led to the expected alcohols in up to 94% ee [34]. 

As described in the catalytic enantioselective borane reduction of ketones using oxazaphospholidine-borane complexes, a mechanistic rationale has been proposed. Nevertheless, this mechanism cannot fully explain the enantioselec-tivity encountered. 

These different complexes have been used as catalysts in the enantioselective borane reduction of acetophenone (THF, r.t.) (Table 4) and the results obtained have permitted one to discover several key features about the catalyst essential for high activity. 

Table 5. Enantioselective borane reduction of various ketones with 2 mol% of 46...

The first successful example of the enantioselective borane reduction of aryl alkyl ketones was performed by using (S)-diphenylvalinol 2. The corresponding alcohols are obtained in up to 100% ee using borane-THF and 0.5 equiv. of 2 in... 

The structurally more rigid (S)-prolinol-based amino alcohol was introduced early in the study of borane reductions [18]. Sterically more hindered ox-azaborolidines 4 (Fig. 1) based on (S)-(-)-diphenylhydroxymethylpyrrolidine have been prepared by Corey [23,25]. These catalysts have been widely used for the borane reduction of various kinds of ketones. After these successful results had appeared for asymmetric ketone reduction, several oxazaborohdines (Fig. 1) were prepared. Many of them were successfully used in the reduction of aromatic ketones. Selected results of enantioselective borane reduction using various oxazaborohdines are shown in Scheme 4. The table to this scheme shows only the data obtained from the reduction of acetophenone as a representative aromatic ketone. In most cases, high enantioselectivity is obtained in the nearly quantitative yield. 

Enantioselective Borane Reduction with Other Lewis Acid Catalysts... 

Fu, l.-P. and Uang, B.-J., Enantioselective borane reduction of aromatic ketones catalyzed by chiral aluminum alkoxides. Tetrahedron Asymmetry, 12 1,45-48, 2001. Experimental- Al[OCH(CH3)2]3 was obtained from commercial manufacture (Oiat-tem Chemicals) and maintained in liquid form by storage at 85"C in a sealed can for >6 months. Double distilled A1[0(CH3)CH2CH2CH3]3 was used as supplied from commercial production (Chattem Chemicals). 70 30 wt% AlP/ASB was prepared from freshly made commercial aluminum isopropoxide and aluminum sec-butoxide. Tolu-... 

COREY Oxidizing reagents for alcohols 78 COREY Enantioselective borane reduction 77 COREY Homologatne epaxidation 78 COREY - KIM Oxidizing reagent 79 COREY-WINTERAlkenesynthesis 80 CORNFORTH Rearrangement 81 Crafts 131... 

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