Chiral ligands, lithium aluminum hydride

In summary, many attempts have been made at achieving enantioselective reduction of ketones. Modified lithium aluminum hydride as well as the ox-azaborolidine approach have proved to be very successful. Asymmetric hydrogenation catalyzed by a chiral ligand-coordinated transition metal complex also gives good results. Figure 6-7 lists some of the most useful chiral compounds relevant to the enantioselective reduction of prochiral ketones, and interested readers may find the corresponding applications in a number of review articles.77,96,97... 

Similar results were obtained with lithium aluminum hydride, using 4 as the chiral ligand, by complexing the dihydridoaluminate-ketone adduct in the transition state, as shown220 in Structure 9. In this case, the optical yield stays below 5%. In all cases described, the S isomer is formed in excess.220... 

Chiral Ligand of L1A1H4 for the Enantioselective Reduction of Alkyl Phenyl Ketones. Optically active alcohols are important synthetic intermediates. There are two major chemical methods for synthesizing optically active alcohols from carbonyl compounds. One is asymmetric (enantioselective) reduction of ketones. The other is asymmetric (enantioselective) alkylation of aldehydes. Extensive attempts have been reported to modify Lithium Aluminum Hydride with chiral ligands in order to achieve enantioselective reduction of ketones. However, most of the chiral ligands used for the modification of LiAlHq are unidentate or bidentate, such as alcohol, phenol, amino alcohol, or amine derivatives. 

Asymmetric Reductions. Asymmetric reductions of prochiral ketones to optically active secondary alcohols have been extensively studied. The most common method involves the use of chiral unidentate or bidentate ligands in conjunction with Lithium Aluminum Hydride. However, an (5)-aspartic acid derived tridentate ligand has been shown to be very effective in certain cases, presumably due to the rigidity of aluminum complex (4) (eq 5-7). ... 

Reduction of Prochiral Ketones. BINOL has been used as the chiral ligand of the reagent BINAL-H (see Lithium Aluminum Hydride-2,2 -Dihydroxy-1,1 -binaphthyl, Vol. B) for asymmetric reduction. The reagent reduces prochiral unsaturated ketones to the corresponding secondary alcohols in up to 90% yield and >90% ee (eq 7) (f )-BINAL-H leads to the (i )-alcohols while (S)-BINAL-H gives the (S)-alcohols. 

Asymmetric hydrogenation. L-Proline has been convened into a series of (S)-2-(aminomethyl)pyrrolidines, such as (S)-2-(anilinomethyl)pyrrolidine (1), d + 19.7°, obtained as shown in equation (I). The product is an efficient chiral ligand for asymmetric reduction of various ketones by lithium aluminum hydride. 

Whilst we were synthesizing (R,R,/ ax)-20a and (5,5,l ax)-20b, RajanBabu and Saha reported their use in the catalytic hydrovinylation of styrene derivatives [66]. However, their 16% yield of the preceding primary phosphine can be improved to quantitative levels [38, 39] by using lithium aluminum hydride in conjunction with chlorotrimethylsilane, and their 5% yield of the phospholanes can now be rationalized at least in part by our isolation of the phenolic compounds R,R,R )-2 a and (5,5,/ ax)-21b. These phenolic phospholanes should prove to be interesting L-X ligands in their own right the parent 2-diphenylphosphino derivative has already been shown to be an effective chiral base in the asymmetric aza-Baylis-Hillman transformations of A-sulfonated imines, by virtue of its phenolic residue [67]. 

---