Monodentate Phosphoramidites: A Breakthrough in Rhodium‐Catalysed Asymmetric Hydrogenation of Olefins

Abstract

Monodentate phosphoramidites based on BINOL or substituted BINOL are excellent ligands for the rhodium-catalysed asymmetric hydrogenation of olefins. Very high enantioselectivities were obtained with MonoPhos (7a) the simplest member of this class, a ligand that is prepared in a single step from BINOL and HMPT. Turnover numbers up to 6000 have been obtained in the hydrogenation of dehydroamino acid derivatives. Enantioselectivities in the hydrogenation of dehydroamino acids are solvent dependent; in non-protic solvents they range from 95 ± 99%. Itaconic acid and its dimethyl ester could be hydrogenated with 96 and 94% e.e., respectively. Hydrogenation of aromatic enamides gave the corresponding acylated amines in 86 ± 94% e.e. Several analogous phosphoramidite ligands have been prepared. Surprisingly, bidentate ligands gave poorer results, both in terms of rate as well as enantioselectivity. Taddol-based phosphoramidites led to poor e.e. and slow rates. Methyl substituents at the 3,3'-position of BINOL led to a sharply reduced rate and a somewhat lower enantioselectivity. Bromo substituents at the 6,6'-position led to a slightly reduced rate but little effect was seen on enantioselectivity. Use of octahydro-MonoPhos (11) gave results that were very similar to those obtained with 7a. The rate of the reaction is dependent on the hydrogen pressure, however, the enantioselectivity is not affected. The rate of the dehydroamino acid hydrogenation also increases if the ligand to rhodium ratio is reduced from 2.2 to 1.5 or even to 1.0; yet, there is no deleterious effect on the enantioselectivity. Catalytic activity ceases with L/Rh 3 when dehydroamino acid derivatives were used as substrate. The reaction shows a positive non-linear effect, which confirms the presence of Rh-complexes with more than one ligand. Following the hydrogenation of methyl 2-acetamidocinnnamate with Rh(nbd) 2 BF 4 /7a by electrospray mass spectrometry showed the presence of several rhodium species. Notable are the presence of [Rh(7a)] 3 and [Rh(7a)] 4 . There is at present insufficient evidence to conclude if the active catalytic species carries one or two ligands. In view of the low cost of MonoPhos this invention might well lead to a broader application of asymmetric olefin hydrogenation for the production of enantiopure amino acids and amines.

Enantioselective Hydrogenation of Enamines with Monodentate Phosphorus Ligands

“…For the hydrogenation of N-(1-(4-chlorophenyl) vinyl)acetamide (7e, Table 8.1) with ligand 4, the product amine 8e was produced in only 44% ee with the opposite configuration compared to the product obtained with MonoPhos ligand. In contrast, the introduction of substituents such as Br at the 6-and 6 0 -positions of MonoPhos, ligand 5, has little effect on the enantioselectivity [24].…”

Asymmetric Hydrogenation of Imines

“…Pizzano et al reported the synthesis of chiral biphenyl-based phosphine-phosphite ligands and evaluated their efficacy in hydrogenating N-arylimine substrates, giving up to 85% ee [77]. Although the monodentate phosphoramidite ligands such as MonoPhos (Scheme 26) have been widely used in the hydrogenation of substrates of enamides [78] and olefins [79], the search for their usefulness in Ir-catalyzed imine hydrogenation have been limited. With an additional achiral nitrogen donor such as 2,6-lutidine and acridine, Faller et al were able to prepare a cationic Ir complex of MonoPhos with BARF as the counterion.…”

Catalytic asymmetric transformations with fine-tunable biphenol-based monodentate ligands

“…[7][8][9]13 Since the early work of Reetz and Mehler, 51 Feringa and co-workers, 7,52 and Claver et al, 53 a number of new monodentate phosphorus ligands have been developed. 4,[7][8][9][10][11][12][13]54 However, newer and more efficient chiral ligands along this line are clearly needed to achieve excellent enantiopurity and high catalyst efficiency for particular substrates and reactions. We describe here the application of a new class of chiral biphenol-based monophosphite ligands 13 to the Rh(I)-catalyzed asymmetric hydrogenation of dimethyl itaconate and discussions about the possible active catalyst species.…”