Valine asymmetric reduction

Later, Maikov and Kocovsky reported the asymmetric reduction of imines with A -methyl L-valine derivative 37 with high yield and enantioselectivity (Scheme 29) [103]. 

High stereoselectivities (94-100 %) are attained in the reduction of aromatic ketones by use of a new chiral borane complex with (S)-2-amino-3-methyl-l,l-diphenylbutan-l-ol,(S-68) readily prepared in two steps from (S)-valine, in an experimentally convenient procedure961. (S)-Valine methyl ester hydrochloride was converted with excess of phenylmagnesium bromide into (S-68). The same treatment of (R)-valine gave (R-68). In a typical asymmetric reduction the reagent, prepared from (S-68) and borane, and the ketone (69) in tetrahydrofuran were kept at 30 °C for some hours. The corresponding alcohols were obtained in high optical purity. (S-68) could be recovered to more than 80% without racemization 96). 

On a poly-L-valine-coated graphite electrode, the asymmetric reduction of the C=C bond in 2-methylcoumarin and in citraconic acid produced ee s of 43% and 25%, respectively Earlier, methyldihydrocoumarin was obtained only with an ee of 18.6% using spartein as an asymmetric inductor... 

Asymmetric reduction ofketimmes found to achieve high enaniioselectix of Itsuno, prepared from BH.t and (S derived from (S)-valine, (12,31). is the Like Corey s oxazaborolidines derised amounts. The highest enantioselectiv aromatic ketones (as high as 88% ce of N-r-butylimines of aryl ketones (8<> dialkyl ketones with 1 results in ( -... 

Asymmetric reduction of ketimines to sec-aminesf Of the various hydride reagents found to achieve high enantioselective reduction of ketones, the oxazaborolidine 1 of Itsuno, prepared from BH3 and (S)-(—)-2-amino-3-methyl-I,l-diphenylbutane-l-ol, derived from (S)-valine, (12,31), is the most effective in terms of asymmetric induction. Like Corey s oxazaborolidines derived from (S)-proline, 1 can also be used in catalytic amounts. The highest enantioselectivities obtain in reduction of N-phenylimines of aromatic ketones (as high as 88% ee). The enantioselectivities are lower in the case of N-t-butylimines of aryl ketones (80% ee). Reduction of N-phenylimines of prochiral dialkyl ketones with 1 results in 10-25% ees. 

Maikov, Kocovsky, and co-workers have developed different L-valine-based Lewis basic catalysts such as 81 [176, 177], for the efficient asymmetric reduction of ketimines 76 with trichlorosilane 2, or catalyst 82 [178] with a fluorous tag, which allows an easy isolation of the product and can be used in the next cycles, while preserving high enantioselectivity in the process. Sigamide catalyst 83 [179, 180] and Lewis base 84 [181] were employed in a low amount (5 mol%) affording final chiral amines 80 with high enantioselectivity (Scheme 30) [182]. Interestingly, 83 was used for the enantioselective preparation of vicinal a-chloroamines and the subsequent synthesis of chiral 1,2-diaryl aziridines. In these developed approaches the same absolute enantiomer was observed in the processes. 

Fig. U.4 Reaction sequence showing how a small e.e. of the reagent is converted to a large e.e. of the product by a metal-assisted reaction. In the case shown, a 1 % e.e. of L-valine produced a 51 % e.e. of L-pyrimidine alcohol by the reductive asymmetric transfer of an isopropyl group from zinc to the carbonyl carbon of the...

Subsequently, List reported that although the method described above was not applicable to the reduction of a,P-unsaturated ketones, use of a chiral amine in conjunction with a chiral anion provided an efficient and effective procedure for the reduction of these challenging substrates [210]. Transfer hydrogenation of a series of cyclic and acyclic a,P-unsaturated ketones with Hantzsch ester 119 could be achieved in the presence of 5 mol% of valine tert-butyl ester phosphonate salt 155 with outstanding levels of enantiomeric control (Scheme 64). A simple mechanistic model explains the sense of asymmetric induction within these transformations aUowing for reliable prediction of the reaction outcome. It should also be noted that matched chirality in the anion and amine is necessary to achieve high levels of asymmetric induction. 

Reductive amination reactions of keto acids are performed with amino acid dehydrogenases. NAD-dependent leucine dehydrogenase from Bacillus sp. is of interest for the synthesis of (S)-fert.-leucine [15-17]]. This chiral compound has found widespread application in asymmetric synthesis and as a building block of biologically active substances. The enzyme can also be used for the chemoenzy-matic preparation of (S)-hydroxy-valine [18] and unnatural hydrophobic bran-ched-chain (S)-amino acids. NAD-dependent L-phenylalanine dehydrogenase from Rhodococcus sp. [19] has been used for the synthesis of L-homophenyl-alanine ((S)-2-Amino-4-phenylbutanoic acid) [9]. These processes with water-soluble substrates and products demonstrate that the use of coenzymes must not... 

Asymmetric variants of imine reduction have also been developed towards enantiopure aziridines. Reduction of chiral /V-tert-butanesulfinyl a-halo imines afforded enantiopure aziridines in good to excellent yields <07JOC3211>. Enantioselective catalytic reduction of a-chloroimines utilizing metal-free L-valine-derived formamide 45 followed by base-mediated ring closure provided aziridines with preserved enantiopurity <07AG(I)3722>. 

Asymmetric hydride reduction using Hantzsch ester has recently been extensively explored in organocatalysis using iminium-based catalysts or Brpnsted acid catalysts [72a-c], As an advance to their asymmetric conterion-directed catalysis (ACDC), List and coworkers found that the combination of simple primary amino acids such as L-valine with a chiral phosphoric acid led to an effective primary aminocatalyst for asymmetric transfer hydrogenation of a,P-unsaturated ketones (Scheme 5.43) [72d]. The catalysis could be applied to a range of substrates with good yields and excellent enantioselectivity. 

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