Asymmetric reduction oxazaborolidine catalyst

The aziridine carbinols are also effective ligands in the preparation of oxazaborolidine catalysts for the asymmetric ketone reduction with borane (Fig. 4) [551. 

Kragl and Wandrey made a comparison for the asymmetric reduction of acetophenone between oxazaborolidine and alcohol dehydrogenase.[59] The oxazaborolidine catalyst was bound to a soluble polystyrene [58] and used borane as the hydrogen donor. The carbonyl reductase was combined with formate dehydrogenase to recycle the cofactor NADH which acts as the hydrogen donor. Both systems were run for a number of residence times in a continuously operated membrane reactor and were directly comparable. With the chemical system, a space-time yield of 1400 g L"1 d"1 and an ee of 94% were reached whereas for the enzymatic system the space-time yield was 88 g L 1 d"1 with an ee of >99%. The catalyst half-life times were... 

Oxazaborolidine catalysts behave like an enzyme in the sense of binding with both ketone and borane, bringing them close enough to undergo reaction and releasing the product after the reaction. Thus these compounds are referred to as chemzymes by Corey.78 The oxazaborolidines listed in Figure 6-6 are representative catalysts for the asymmetric reduction of ketones to secondary alcohols. 

Addition of triethylamine to the oxazaborolidine reaction system can significantly increase the enantioselectivity, especially in dialkyl ketone reductions.79 In 1987, Corey et al.80 reported that the diphenyl derivatives of 79a afford excellent enantioselectivity (>95%) in the asymmetric catalytic reduction of various ketones. This oxazaborolidine-type catalyst was named the CBS system based on the authors names (Corey, Bakshi, and Shibata). Soon after, Corey s group81 reported that another fi-methyl oxazaborolidine 79b (Fig. 6-6) was easier to prepare and to handle. The enantioselectivity of the 79b-catalyzed reaction is comparable with that of the reaction mediated by 79a (Scheme 6-36).81 The -naphthyl derivative 82 also affords high enantioselectivity.78 As a general procedure, oxazaborolidine catalysts may be used in 5-10 mol%... 

Asymmetric reduction of aryl a-ketoimines, by the use of oxazaborolidine catalysts, gives a good ee of the resultant alcohol (equation 82)332. The product is an arylethanolamine which is a synthetic target (e.g. /1-blockers) and a useful intermediate. 

A polymer-enlarged homogeneously soluble oxazaborolidine catalyst for the asymmetric reduction of ketones by borane, Tetrahedron Asymm. 1997, 8, 1975-1977. 

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. 

The use of chiral oxazaborolidines as catalysts for the enantioselective addition of alkynylboranes to aldehydes took place in a manner analogous to the asymmetric reduction of ketones with boranes mediated by proline-derived oxazaborolidines (Equation (127)).587 Addition of alkynylboranes to A-aziridinylimines provided a convenient method to prepare allenes from carbonyl compounds (Equation (128)).5... 

We have also examined the use of chiral bi-2-naphthol to resolve some other racemic amino alcohols. The S-diphenylpyrrolidinemethanol S-10, synthesised from S-proline is useful in the preparation of the CBS oxazaborolidine catalyst,16 widely used in catalytic asymmetric reductions. Accordingly, the corresponding R-10 enantiomer is also a valuable chiral compound. 

The use of oxazaborohdines as asymmetric reduction catalysts and the enantioselectivity of diphenyloxazaborohdine reduction of ketones have been reviewed. Large-scale practical enantioselective reduction of prochiral ketones has been reviewed with particular emphasis on the Itsimo-Corey oxazaborolidine and Brown s 5-chlorodiisopinocampheylborane (Tpc2BCl) as reagents. Brown himself has also reviewed the use of Ipc2BCl. Indohnoalkylboranes in the form of dimers have been confirmed by B NMR as the products of the reduction of trifluoroacetylindoles by diborane. ... 

In particular, asymmetric reduction of ketones to alcohols has become one of the more useful reactions. To achieve the selective preparation of one enantiomer of the alcohol, chemists first modified the classical reagents with optically active ligands this led to modified hydrides. The second method consisted of reaction of the ketone with a classical reducing agent in the presence of a chiral catalyst. The aim of this chapter is to highlight one of the best practical methods that could be used on an industrial scale the oxazaborolidine catalyzed reduction [1]. 

One of the most powerful asymmetric catalytic reductions of ketones is borane reduction with oxazaborolidine catalyst [92, 93]. Various types of polymer-supported chiral amino alcohols have been prepared and used for the formation... 

Scheme 7.3. Catalytic cycle for the asymmetric reduction of a ketone with an oxazaborolidine catalyst [29,35,36],...

For the oxazaborolidine (27), ab initio molecular orbital calculations <94JA8516> and semiempirical methods <93JOC799, 94TA903> have been used to investigate possible transition-state assemblies that correspond to catalyst-borane complexes in asymmetric reduction pathways. Various key intermediates have been proposed depending on the level of theory adopted. 

The use of oxazaborolidine catalysts in asymmetric reductions of ketones has been extensively studied by Corey et al. Recently, a polymer-bound oxazaborolidine Scheme 3.6.5) was developed and successfully used in the asymmetric reduction of acetophenone. 1-Phenylethanol was obtained in 93% yield and 98% enantiomeric excess. 

A more-efficient method for asymmetric reduction uses the chiral inducing agent as a catalyst. A suitable system involves the oxazaborolidine 111, which can be prepared from the corresponding amino-alcohol and methylboronic acid, or is available commercially in either enantiomeric form Addition of borane to this... 

Scheme 5. Mechanism of the asymmetric reduction of carbonyl compounds (e. g. 25) with borane and chiral oxazaborolidine catalysts (e. g. 26).

The past fifteen years witnessed the development of oxazaborolidines as catalysts for various organic reactions (44). The Itsuno-Corey asymmetric reduction is a prominent example (Figure 12) (45, 46). This chemistry led... 

Chiral oxazaborolidine catalysts were applied in various enantioselective transformations including reduction of highly functionalized ketones/ oximes or imines/ Diels-Alder reactions/ cycloadditions/ Michael additions, and other reactions. These catalysts are surprisingly small molecules compared to the practically efficient chiral phosphoric acids, cinchona alkaloids, or (thio)ureas hence, their effectiveness in asymmetric catalysis demonstrates that huge substituents or extensive hydrogen bond networks are not absolutely essential for successful as5unmetric organocatalysis. 

Borane is one of the most common agents for reducing C=0 and C=N bonds and its applications for the enantioselective reduction of ketones and imines have been extensively studied in past decades [77]. Among such agents, the Corey-Bakshi-Shibata (CBS) catalyst, a chiral oxazaborolidine complex, which was discovered by Itsuno in 1981 [78] and further developed by Corey in 1987 [79], was widely considered as the most successful catalytic system. Several excellent reviews are already available [77a, 80]. In this chapter, we only give limited coverage of the organocatalytic asymmetric reduction of ketones by catalytic systems other than chiral oxazaborolidines. 

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