Tuning of the Structures of Chiral Phosphane‐Phosphites: Application to the Highly Enantioselective Synthesis of α‐Acyloxy Phosphonates by Catalytic Hydrogenation

Abstract

A family of new chiral phosphane-phosphites 5 has been prepared and employed in the synthesis of rhodium complexes of formulation [Rh(cod)(5)]BF4 (7). The use of bulky phosphane or phosphite groups in the preparation of 7 avoids the formation of undesired disubstituted complexes, one of which (9 a) has been isolated and characterized. Ligands 5 display important differences from the bulkier phosphane-phosphites 1: complexes 7-unlike their rigid [Rh(cod)(1)]BF4 counterparts-show fluxional behaviour in solution, consistent with backbone oscillation around the coordination plane. A detailed screening of ligands 1 and 5 in catalytic asymmetric hydrogenations of enol phosphonates 12 demonstrated a critical influence of the steric characteristics of the phosphane-phosphite in the course of the reaction, and optimization of the two phosphorus functionalities resulted in the production of versatile and efficient catalysts for this class of hydrogenations: enantioselectivities of up to 98% ee were thus obtained with substrates bearing an alkyl substituent in the beta-position, while for their challenging aryl counterparts values of up to 92% ee were achieved. The coordination mode of phosphonate 12 a towards a Rh phosphane-phosphite fragment has also been investigated and a preference of the olefin fragment to occupy the position cis to the phosphite group has been observed. From this observation an interpretation of the configurations of the hydrogenated phosphonates has also been made.

The synthesis of P-stereogenic MOP analogues and their use in rhodium catalysed asymmetric addition

“…The few cases where such hybrid ligands were studied have proved inconclusive. Thus, for example, in the case of asymmetric hydroformylation, Pizzano and co-workers found that their PeOP ligands which combined both axial and P-stereogenicity were less selective than their ligands without P-stereogenicity, suggesting that the chiralities were not co-operative [4,5].Conversely, Buchwald and co-workers have reported significantly improved ees when their P-stereogenic binaphthyl substituted monophosphines were tested in palladium catalysed asymmetric vinylation and arylation reactions [6,7]. Previously our group have reported the novel synthesis of P-stereogenic MOP analogues ( Fig.…”

Highly Enantioselective Hydrogenation of Enol Ester Phosphonates: A Versatile Procedure for the Preparation of Chiral β‐Hydroxyphosphonates

“…Thus, among the catalysts investigated, that derived from phosphane–phosphite 4 b produced excellent results, giving full conversion and affording 2 a with excellent chemo‐ and enantioselectivity (Table 1, entry 2). Interestingly, catalysts based on ligands 4 a and 4 b had low activity in the hydrogenation of related α‐acyloxyphosphonates 16b…”

Readily available chiral phosphine–aminophosphine ligands derived from 1-phenylethylamine for Rh-catalyzed enantioselective hydrogenations

“…[3,5-bis(trifluoromethyl)phenyl]phosphino}-(S)-1- [2-(diphenylphosphino) 6,53.7,122.8,123.1 (q,J = 271 Hz),125.7,127.6,128.5,128.6,128.9,129.5,130.7,130.9,131.1,131.8,131.9,133.7,133.9,134.1,144.0,144.2,149.7;: m/z = 761.1280, calcd for C 36 H 25 F 12 NP 2 (M + ): 761.1271. (3,5-difluorophenyl)phosphino]-(S)-1- [2-(diphenylphosphino) 2,45.9,59.8,125.1,126.5,126.9 (J = 271 Hz),127.4,128.4,128.5,128.6,128.7,129.1,133.7,133.9,134.1,134.7,134.9,135.5,135.7,140.8,148.9 3, 22.7, 59.9, 126.8, 126.9, 128.4, 128.5, 128.6, 128.8, 129.1, 131.8, 132.0, 132.7, 132.9, 133.8, 134.0, 137.6, 150.2, 150.5 7,59.8,122.8,123.2 (q,J = 271 Hz),126.2,127.8,128.5,…”

“…However, this does not mean that C 2 symmetry is essential for ligand design. In fact, the past decade has witnessed significant advancement in the use of unsymmetrical hybrid bidentate phosphorus ligands such as phosphine-phosphoramidite ligands, 6 phosphine-phosphite ligands 7 , and phosphine-aminophosphine ligands 8 for catalytic asymmetric hydrogenation. These types of ligands normally display excellent performance in a variety of asymmetric hydrogenations, comparable to or even higher than those obtained with C 2 -symmetrical ligands.…”