The asymmetric hydrogenation of aryl- and alkyl-substituted enamides catalyzed by Rh-BisP complex affords optically active amides with very high ee values. The Rh-MiniPHOS catalyst gives somewhat less satisfactory results. Hydrogenation of the aryl-substituted enamides with (S,S)-BisP-Rh catalyst gives R-amides, whereas the t-Bu- and 1-adamantyl-substituted enamides give S-products with 99% ee. Reaction of [Rh(BisP)(CD(3)OD)(2)]BF(4) (11) with CH(2)=C(C(6)H(5))NHCOCH(3) (5) gives two diastereomers of the catalyst-substrate complex (12a,b), which interconvert reversibly by both intra- and intermolecular pathways as shown by EXSY data. Only one isomer in equilibrium with solvate complex 11 was detected for each of the catalyst-substrate complexes 17 and 18 obtained from CH(2)=C(t-Bu)NHCOCH(3) (6) or CH(2)=C(1-adamantyl)NHCOCH(3) (7). Hydrogenation of these equilibrium mixtures at -100 degrees C gave monohydride intermediates 19 and 20, respectively. In these monohydrides the Rh atom is bound to the beta-carbon. A new effect of the significant decrease of ee was found for the asymmetric hydrogenation of CH(2)=C(C(6)H(4)OCH(3)-o)NHCOCH(3) (21), when H(2) was substituted for HD or D(2).

A new class of chiral C2‐symmetric bis(trialkyl)phosphine ligands has been prepared and used in Rh(I)‐catalyzed asymmetric hydrogenation reactions. The ligands, 1,2‐bis(alkylmethylphosphino)ethanes 1a‐g(abbreviated as BisP*, alkyl = t‐butyl, 1‐adamantyl, 1‐methylcyclohexyl, 1,1‐diethylpropyl, cyclopentyl, cyclohexyl, isopropyl) and 1,2‐bis(alkylmethylphosphino)methanes 2a‐d(abbreviated as MiniPHOS, alkyl = t‐butyl, cyclohexyl, isopropyl, phenyl) are prepared by a simple synthetic approach based on the air‐stable phosphine–boranes. These new ligands give the corresponding Rh(I) complexes, which are effective catalytic precursors for the asymmetric hydrogenation of a representative series of dehydroamino acids and itaconic acid derivatives. Enantioselectivities observed in these hydrogenations are universally high and in many cases exceed 99%. X‐Ray characterization of four precatalysts, study of the pressure effects, deuteration experiments, and characterization of the wide series of intermediates in the catalytic cycle are used for the discussion of the possible correlation between the structure of the catalysts and the outcome of the catalytic asymmetric hydrogenation.

Excellent enantioselectivities up to 99.7% were achieved in the hydrogenation of (E)-beta-(acylamino)acrylates by the use of Rh(I)-complexes of electron-rich diphosphines, t-Bu-BisP and t-Bu-MiniPHOS. Low-temperature NMR experiments testify that monohydrides with beta-carbon atom of the substrate bound to rhodium are involved in the catalytic cycle.

A series of bis(phosphanes) (S P ,S PЈ )-R 1 (Me)PCH 2 CH 2 PЈR 2 R 3 (1a−k; R 1 , R 2 , and R 3 = 1-adamantyl, tert-butyl, cyclohexyl, cyclopentyl, isopropyl, methyl, phenyl; abbreviated as unsymmetrical BisP*) has successfully been synthesized, by coupling of the (R P )-configured tosylates 5a−d or mesylates 6a−g with lithiated (S P )-R 1 (Me)PH−BH 3 adducts. Asymmetric hydrogenations catalyzed by rhodium complexes of the unsymmetrical BisP* moieties as ligands revealed extremely high enantioselectivities − 99% (9b) and 98% (9e) − when the trisubstituted and tetrasubstituted dehydro-α-amino acid derivatives 8b and 8e, respectively, were used as substrates.

Optically active 1,2-bis(alkylmethylphosphino)ethanes and bis(alkylmethylphosphino)methanes are unique diphosphine ligands combining the simple molecular structure and P-stereogenic asymmetric environment. This work shows that these ligands exhibit excellent enantioselectivity in rhodium-catalyzed asymmetric hydrogenation of ␣,␤-unsaturated phosphonic acid derivatives. The enantioselective hydrogenation mechanism elucidated by NMR study is also described. The ␣-hydroxy-and ␣-aminophosphonic acids have an extremely rich and varied spectrum of biological activity (1, 2) that is stipulated by their ability to act as antagonists for amino acids inhibiting enzymes involved in the amino acids' metabolism. They can be used as herbicides (3, 4), antiviral drugs (5), antibiotics (6), and neurodrugs (7). Being able to affect the biological activity of cells (8), some of them can inhibit HIV protease (9) and alanine racemase (alafosfalin) (10). Peptide ␣-hydroxyphosphonates are known to be rennin inhibitors (11).The biological activity of the phosphonic acids highly depends on the absolute configuration of its ␣-chiral center. An excellent example is alafosfalin, [N-(L-alanyl)-L-1-aminoethyl]phosphonic acid (S,R)-diastereomer. Only this diastereomer unlike (R,R)-, (S,S)-, and (R,S)-diastereomers shows high antibacterial activity (12, 13).Development of the synthesis of optically active ␣-hydroxyand ␣-aminophosphonic acids has begun only recently (2, 15). ʈ Processes applying the catalytic amounts of the source of chirality are especially attractive. Thus, hydrophosphonylation of imines catalyzed by heterobimetallic complexes Ln-K-BINOL (16) and hydrophosphonylation of aldehydes catalyzed by analogous complexes Al-Li-BINOL (17) give the ␣-amino-and ␣-hydroxyphosphonic acids, respectively, with high enantiomeric excesses (ee's). Furthermore, the catalytic asymmetric Michael addition to ␣,␤-unsaturated phosphonates (18, 19) and the allylation reaction of ␣-acetylamino-␤-ketophosphonates (20) have been successfully used for the synthesis of phosphonic acid derivatives with the stereogenic centers in the ␣-or ␤-position.Another convenient approach to the synthesis of the acids is the asymmetric hydrogenation of the corresponding unsaturated precursors. By this means, the phosphorus analogs of ␣-aminoor ␣-hydroxycarboxylic acids were obtained with up to 96% ee by using the Rh complexes of chiral phosphine ligands such as (Ϫ)-BPPM (2S,4S) (21) and DuPHOS (22). Noyori and coworkers reported that ␣-substituted ␤-ketophosphonates were subjected to enantio-and diastereoselective hydrogenation by the use of the BINAP-Ru(II) complex to give the corresponding ␤-hydroxyphosphonates with exceedingly high ee's (94-98%) (23,24). Also worth mentioning is that optically active ␣-arylsubstituted ethylphosphonates, phosphorus analogs of 2-arylpropionic acids, were produced by Ir-and Ru-catalyzed asymmetric hydrogenation of ethenylphosphonates (25,26).On the other hand, we previously designed and synthesized new bidentate phosphine ligands, (S,S...