Oxazaborolidine catalysts

Reduction of carbonyl compounds with chiral oxazaborolidine catalysts 98AG(E)1987. 

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

Corey, E.J. Helal, C.J. (1998) Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method. Angewandte Chemie International Edition, 37, 1986-2012. 

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

Fig. 5.7. Crystal structure of borane complex of a,a-diphenylprolinol oxazaborolidine catalysts. Reproduced from...

The use of such an oxazaborolidine system in a continuously operated membrane reactor was demonstrated by Kragl et /. 58] Various oxazaborolidine catalysts were prepared with polystyrene-based soluble supports. The catalysts were tested in a deadend setup (paragraph 4.2.1) for the reduction of ketones. These experiments showed higher ee s than batch experiments in which the ketone was added in one portion. The ee s vary from 84% for the reduction of propiophenone to up to >99% for the reduction of L-tetralone. The catalyst showed only a slight deactivation under the reaction conditions. The TTON could be increased from 10 for the monomeric system to 560 for the polymer-bound catalyst. 

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%... 

The effect of changing the position of the electron-donating atom in the side chain R of oxazaborolidine catalysts 367 was studied systematically for the reaction between cyclopentadiene and methacrolein. The enantioselectivity proved to be controlled by the presence of electron-donor atoms at positions 2 and 4 of the side chain. The effect was especially apparent in the formation of 366 from cyclopentadiene with a-bromoacrolein (365) (equation 105, Table 20), which is more electron-poor than methacrolein232. 

Very high enantioselectivities were obtained in the reaction between cyclopentadiene and a-bromoacrolcin using (S )-tryptophan derived oxazaborolidine catalyst (S)-369b. The Diels-Alder adduct (2R)-366 was obtained with at least 99% enantiomeric excess233. 

Cross-linked polymers bearing IV-sulfonyl amino acids as chiral ligands were converted to polymer bound oxazaborolidine catalysts by treatment with borane or bromoborane. In the cycloaddition of cyclopentadiene with methacrolein, these catalysts afforded the same enantioselectivities as their non-polymeric counterparts238. 

The proposed catalytic cycle for reduction of acetophenone is illustrated in Figure 1.28. The (5)-oxazaborolidine catalyst (5)-28A has both Lewis acidic and basic sites, and its borane adduct 28B acts as a chiral Lewis acid. The B center in the borolidine ring selectively interacts with a stericaUy more accessible electron... 

Scheme 5.4. Enantionselective Reduction of Ketones Using Oxazaborolidine Catalyst... 

The characteristic feature of the aforementioned oxazaborolidine catalyst system consists of a-sulfonamide carboxylic acid ligand for boron reagent, where the five-membered ring system seems to be the major structural feature for the active catalyst. Accordingly, tartaric acid-derived chiral (acyloxy)borane (CAB) complexes can also catalyze the asymmetric Diels-Alder reaction of a,P-unsaturated aldehydes with a high level of asymmetric induction [10] (Eq. 8A.4). Similarly, a chiral tartrate-derived dioxaborolidine has been introduced as a catalyst for enantioselective Diels-Alder reaction of 2-bromoacrolein [11] (Eq. 8A.5). 

Kiyooka et al. have shown that the asymmetric aldol reaction of ketene silyl acetals is promoted by 20 mol % of oxazaborolidine catalyst derived from (5)-valine with enantioselectivity employing nitromethane as the solvent [47]. 

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. 

S -Methyl lactate gives a poor ee in hydroboration of acetophenone, but ZnCl2 raises it.322 A molecular orbital method has looked at the enantioselectivities associated with four oxazaborolidine catalysts acting on phenyl methyl ketone.323 0>... 

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

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

Corey EJ, Helal CJ (1998) Reduction of carbonyl compounds with chiral oxazaborolidine catalysts a new paradigm for enantioselective catalysis and a powerful new synthetic method. Angew Chem Int Ed 37 1986-2012... 

Addition of lithium bis(trimethylsilyl)amide to perfhiorinated ketones and solvolysis of the N-Si bond in methanol resulted the formation of stable, isolable N-H imine Z-E isomer mixtures along with a methanol adduct. Enantioselective reduction of these three-component mixtures with oxazaborolidine catalysts and catecholborane provided trifluoromethylated amines in 72-95% yields and 75-98% ee 267... 

Mechanistic studies41"43 by Dixon and Jones excluded the possibility of dimeric catalytic species because a linear dependence was observed between the catalyst s enantiopurity and the reaction s enantioselectivity.43 The test reaction was the desymmetrization of meso-imide 22 using chiral oxazaborolidine catalysts. The sense of the enantioselectivity of the reduction was established by conversion of hydroxy lactam 23 to the known ethoxy lactam 24 (Scheme 17.6). 

Nickel boride prepared from Nil2 and two equivalents of LiBH4 [42] was utilized as an oxazaborolidine catalyst support (Scheme 4) [43]. Reaction of nickel boride with 0.1 equivalents of chiral amino alcohol in THF at room temperature gave the anchored catalyst 6, which produced chiral alcohols in optical yields of up to 95%, and which furthermore showed higher activity as regards the reduction of acetophenone derivatives than that of the corresponding homogene-... 

R) -1 on a preparative scale. Variation of several reaction parameters such as catalyst loading, solvent, temperature, and addition order, have led to the development of an optimized procedure for this reduction. To achieve a selectivity of >90% ee, the reaction requires the use of 10 mol% of the oxazaborolidine catalyst, which is easily prepared in two steps from natural proline4 or in one step from commercially available... 

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. 

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