Asymmetric boranes

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>. 

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

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... 

SCHEME 19. Asymmetric borane reduction of ketones catalyzed by an oxazaphos-pholidine-borane complex. 

SCHEME 17. Synthetic application chiral secondary alcohols produced by the asymmetric borane reduction. 

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... 

Figure 48. Catalytic, asymmetric borane reduction with the new chiral La complex.

Asymmetric Borane Reduction. The reaction of ATBH with trimethylboroxine by refluxing in toluene affords the chiral B-methyl oxazaborolidine in high yield (eq 2) This oxaz-aborolidine can serve as an efficient catalyst for the asymmetric borane reduction ofprochiral ketones (eq 3). The corresponding chiral secondary alcohols are obtained in high yields with good enantioselectivities. 

The in situ generated catalyst from ATBH and trimethyl borate has also been used in the stereoselective reduction of a-oxoketoxime ethers to prepare the corresponding chiral 1,2-amino alcohols. Thus the asymmetric borane reduction of buta-2,3-dione monoxime ether followed by acidic work-up and subsequent reaction with benzyloxycarbonyl chloride affords a 90% yield of 7V-(Z)-3-aminobutan-2-ol with excellent enantioselectivities (eq 5). A trityl group in the oxime ether is required for high enantioselectivity. This method has been successively applied to both cyclic and acyclic a-oxoketoxime ethers. 

Reaction of ATBH with trimethyl borate in THF presumably affords the B-methoxy oxazaborolidine, which effectively catalyzes asymmetric borane reduction of prochi-ral ketones. Thus the borane reduction of acetophenone with the reagent prepared in situ from 0.1 equiv of ATBH and 0.12 equiv of trimethyl borate provides... 

The modified procedure for asymmetric borane reduction is applicable to the stereoselective synthesis of N-benzoylsphinganine. Reduction of a-oxoketoxime trityl ethers 1 and 2 using catalyst prepared in situ from (lB,2B,3S,5/ )-ATBH and trimethyl borate proceeds in high yields with high enantioselectivities (eq 6). Satisfactory results are obtained by employing the borane-Af, -diethylaniline complex as a reducing agent. In the reduction of substrate 1, the predominant diastereomer is threo. On the other hand, the... 

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. 

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>. 

The synthesis of various new chiral (o-hydroxyaryl)oxazaphospholidine oxides (139), derived from (S)-proline derivatives, from precursors (140) have been elaborated. This two-step reaction involves an unstable metallated intermediate that undergoes a fast 1,3-rearrangement with the formation of phosphorus-carbon bond. These catalysts have been successfully applied to the catalytic asymmetric borane reduction of numerous prochiral ketones with enantiomeric excess up to 84% ee (Scheme 35). ... 

Based on these studies, Vasella et al. have described the synthesis of a glyco-sylphosphine-borane complex 20 and its use as catalyst (2 mol%) in asymmetric borane reduction of acetophenone at 110 °C with an enantioselectivity up to 24% ee [29]. 

In 1996, our group initiated a program of research dealing with the asymmetric borane reduction of ketones using oxazaphospholidine oxide compounds as catalysts [34]. 

The monolith-type prolinol 165 was prepared from the (trimethylsilyl) ethoxycar bonyl (Teoc)-protected monomers (Scheme 3.48). Although the asymmetric borane... 

Dendrimer-supported prolinol derivahve 166 has been prepared and used as a chiral ligand in the asymmetric borane reduction ofindanones 167 and tetralones (Scheme 3.49) [99]. From substituted indanones or tetralones, ds and trans isomers were obtained in a near 1 1 ratio, tn the case of the reduction of substituted inda-none, the ds isomers had an ee of about 80%, whereas the trans isomers had an ee of about 95%. tn the case of tetralones, ee-values >90% ee were obtained for both the cis and trans isomers. 

Although the catalytic asymmetric borane reductions mentioned above are a powerful tool to obtain highly enantio-enriched alcohols, these require the use of a rather expensive and potentially dangerous borane complex. Sodium borohydride and its solution are safe to handle and inexpensive compared to borane complexes. Thus sodium borohydride is one of the most common industrial reducing agents. However its use in catalytic enantioselective reductions has been limited. One of the most simple asymmetric catalysts is an enantiopure quaternary armnonium salt that acts as phase-transfer catalyst. For instance, in the presence of the chiral salt 81 (Fig. 9), sodium borohydride reduction of acetophenone gave the secondary alcohol in 39% ee [124]. The polymer-supported chiral phase-transfer catalyst 82 (Fig. 10) was developed for the same reduction to give the alcohol in 56% ee [125]. 

Optically active P-hydroxysulfoximines which catalyze the asymmetric borane reduction of ketones [110], also catalyze the same reaction with sodium borohydride/trimethylsilyl chloride system as reducing agent [126]. Reduction of a protected a-hydroxyacetophenone afforded the alcohol with 90% ee. 

A study comparing asymmetric borane reductions of kctoxime ethers and /V-substituted ketimines mediated by selected chiral oxazaborolidines 8-14 has been carried out. The corresponding amines were obtained with up to 99% ee50-52. The enantioselective reduction of imines using chiral dialkoxyboranes has also been the subject of a study60. 

Asymmetric, borane-modified MPV reduction of a variety of aromatic ketones to their corresponding alcohols has recently (43) been reported using a chiral aluminum alkoxide catalyst shown in Figure 5. This compound was formed in situ from aluminum isopropoxide and (R)-l,r-binapthyl-diol in... 

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