Boranes reduction of ketones

Scheme 10.55 Borane reductions of ketones with p-hydroxy sulfoximine ligand.

In order to avoid the use of a rather expensive and potentially dangerous borane complex, Bolm et al. have developed an improved procedure for the borane reduction of ketones, which involved two inexpensive reagents namely NaBH4 and TMSCI. The reduction of a series of ketones was examined applying these novel reaction conditions and the same p-hydroxy sulfoximine ligand to that described above (Scheme 10.56). For most ketones, both the level of asymmetric induction and the yield compared favorably to the precedent results. 

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. 

Scheme 10.60 Borane reductions of ketones with L-methionine-derived S/N ligand.

Scheme 10.65 Ga-catalysed borane reductions of ketones with MTBH2 ligand.

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. 

Bis(pyrazolyl)borate copper complex 47 has been employed as a catalyst in the homogeneous and heterogeneous styrene epoxidation reactions <00JCS(CC)1653>. Pyrazole palladacycles 48 have proven to be stable and efficient catalysts for Heck vinylations of aryl iodides <00JCS(CC)2053>. An asymmetric borane reduction of ketones catalyzed by N-hydroxyalkyl-/-menthopyrazoles has been reported <00JHC983>. 

Enantioselective borane reduction of ketones catalyzed by chiral oxazaborolidines. 

Corey extended the utility of this catalytic hydroboration chemistry remarkably (38). Scheme 15 shows some examples of the highly en-antioselective asymmetric borane reduction of ketones. The well-designed chiral oxazaborolidines, which act as catalyst precursors, have... 

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

Scheme 11.1 also summarizes other impressive examples of the performance of the CBS method [1-8]. Several excellent reviews on the CBS method have appeared recently [1, 2], and no detailed discussion of the development of the process or substrate scope shall be presented in this review. Please note, however, that the oxazaborolidine-catalyzed borane reduction of ketones is a prime example of bi-functional catalysis [2, 9] - as shown in Scheme 11.2, the current mechanistic picture involves simultaneous binding of both the ketone and the borane to the Lewis-acidic (boron) and Lewis-basic (nitrogen) sites of the catalyst A. In the resulting ternary complex B, the reaction partners are synergistically activated toward hydride transfer. 

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... 

Phosphoric amide catalysts for the borane reduction of ketones ... 

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). 

Reduction of C=0 and C=N Bonds. Asymmetric reductions of prochiral ketones (19) to the corresponding chiral alcohols (20) using (S)-proline-modified borohydride reagents as the reductant have been published. The borane reductions of ketones (19) employing (S)-proline as chiral mediator proceeds with enantiomeric... 

Oxazaborolidines have been found to be a unique catalyst for asymmetric borane reduction of ketones and imines [35,36]. Coordination of BH3 to the nitrogen atom of 24 serves to activate BH3 as a hydride donor and to increase the Lewis acidity of the boron atom (Eq. 9). The Lewis acidity of the boron atom in the oxazaborolidine plays an important role in the reduction. Several types of polymer-supported oxazaborolidine have been reported and are considered to be polymer-supported boron-based Lewis acids. 

The first report of a polymer-supported oxazaborolidine appeared in 1985 [37]. The polymer-supported chiral ligand amino alcohol (27) was prepared by reaction of chlor-omethylated polystyrene resin and enantiopure amino alcohol 26 with a phenolic hydroxyl group (Eq. 10). Borane reduction of ketones by use of polymer-supported oxazaborolidines proceeded very smoothly to give the corresponding chiral alcohol in quantitative yield. For example, the reduction of butyl phenyl ketone afforded 1-phe-nylpentan-l-ol in 97 % ee (27, Eq. 11). This is somewhat higher than that obtained by... 

Use of thiaprohnol amino alcohols as hgands for enantioselective borane reduction of ketones and of a fiuorotitanium-TADDOLate to catalyse reduction of benzaldehyde has been described above imder OrganometaUics and Allylation Reactions, respectively. 

Pyrazole and 3,5-dimethylpyrazole were effective stoichiometric catalysts in the Baylis-Hillman reaction of cyclo-pentenone 892 with /i-nitrobenzaldehyde 893 in basic media to give adducts 894 in good yields (Equation 190) <2004TL5171>. An asymmetric borane reduction of ketones catalyzed by AT-hydroxyalkyl-Z-menthopyrazoles has been reported <2000JHC983>. 3-Aryl-/-menthopyrazoles 895 were assessed for their catalytic activity for asymmetric Diels-Alder reactions <2002JHC1235, 2003JHC773>. 

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

A disulfide-linked bis(aminoethanol) 82 prepared from L-cystine also catalyzes the borane reduction of ketones. Other oxazaborolidine derivatives are obtained from 83, 84, " and 85, " and polymer-bound species. Those derived from the ephedra bases find use in the asymmetric reduction of imines. bicyclic oxazaborolidine generated... 

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... 

In 1996, our group initiated a program of research dealing with the asymmetric borane reduction of ketones using oxazaphospholidine oxide compounds as catalysts [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. 

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