Asymmetric hydrogenation of α,β-unsaturated phosphonates with Rh-BisP* and Rh-MiniPHOS catalysts: Scope and mechanism of the reaction

Abstract

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...

Stereoselective synthesis of GABOB, carnitine and statine phosphonates analogues

“…[69][70][71][72] Recently, Pizzano et al 73 reported the synthesis of enantiomerically pure (R)-GABOB P 7 via the highly enantioselective hydrogenation of enol ester phosphonate 84. Thus, the reaction of b-ketopropylphosphonate 83 with NaH followed by the addition of benzoyl chloride (BzCl) afforded the corresponding enol Z-84 as the only isomer isolable, which by catalytic hydrogenation in the presence of complex [Rh(cod) (85)]BF 4 , (cod = cycloocta-1,5-diene) gave the b-benzyloxyphosphonate (R)-86 in 87% yield and 99% ee.…”

Transition Metal‐Catalyzed Homogeneous Asymmetric Hydrogenation

“…Rh complexes of BPE, DuPhos [172] , t Bu -BisP * , t Bu -MiniPhos [173] , and 13 [174] are also studied for the hydrogenation of enol phosphate (Fig. 7.21 ).…”

An overview of stereoselective synthesis of α-aminophosphonic acids and derivatives

“…In 2004, Imamoto et al 151 described that the catalytic hydrogenation of dehydroaminophosphonate 248 in the presence of rhodium complex ( R,R )- t -BuBisP* 249 gave the ( R )-α-aminophosphonate 250 in 90% ee (Scheme 65). …”