Double asymmetric hydrogenation of conjugated dienes: a self-breeding chirality route for C2 symmetric 1,4-diols.

The synthesis and double asymmetric hydrogenation of (Z,Z)-1,3-diene-1,4-diyl diacetates is described. In this reaction C2/meso ratios up to 85 : 15 and enantioselectivities up to 97% ee have been achieved. As the hydrogenation products can be converted into chiral 1,4-diols, key starting materials for the preparation of the best catalysts used, this catalytic system enables a self-breeding chirality process.

Broad Scope Synthesis of Ester Precursors of Nonfunctionalized Chiral Alcohols Based on the Asymmetric Hydrogenation of α,ß-Dialkyl-, α,ß-Diaryl-, and α-Alkyl-ß-aryl-vinyl Esters.

The catalytic asymmetric hydrogenation of trisubstituted enol esters using Rh catalysts bearing chiral phosphine-phosphite ligands (P-OP) has been studied. Substrates covered comprise α,ß-dialkyl, α-alkyl-ß-aryl, and α,ß-diarylvinyl esters, the corresponding hydrogenation products being suitable precursors to prepare synthetically relevant chiral nonfunctionalized alcohols. A comparison of reactivity indicates that it decreases in the order: α,ß-dialkyl > α-alkyl-ß-aryl > α,ß-diaryl. Based on the highly modular structure of P-OP ligands employed, catalyst screening identified highly enantioselective catalysts for α,ß-dialkyl (95-99% ee) and nearly all of α-alkyl-ß-aryl substrates (92-98% ee), with the exception of α-cyclohexyl-ß-phenylvinyl acetate which exhibited a low enantioselectivity (47% ee). Finally, α,ß-diarylvinyl substrates showed somewhat lower enantioselectivities (79-92% ee). In addition, some of the catalysts provided a high enantioselectivity in the hydrogenation of E/Z mixtures (ca. Z/E = 75:25) of α,ß-dialkylvinyl substrates, while a dramatic decrease on enantioselectivity was observed in the case of α-methyl-ß-anisylvinyl acetate (Z/E = 58:42). Complementary deuteration reactions are in accord with a highly enantioselective hydrogenation for both olefin isomers in the case of α,ß-dialkylvinyl esters. In contrast, deuteration shows a complex behavior for α-methyl-ß-anisylvinyl acetate derived from the participation of the E isomer in the reaction.

Features and Application in Asymmetric Catalysis of Chiral Phosphine-Phosphite Ligands.

Chiral phosphine-phosphites are a class of ligands for asymmetric catalysis characterized by two coordinating functionalities with different electronic properties. These ligands also possess a highly modular structure and, due to versatile synthetic processes, they can be tuned precisely in the catalyst optimization process. Research regarding the application of these ligands in several enantioselective catalytic processes has provided outstanding results in a good number of them. These processes include not only Rh catalyzed reactions, such as olefin hydrogenation and hydroformylation, but also other reactions, such as hydrogenation of olefins and imines by Ru complexes, of imines and N-heterocycles by Ir derivatives, allyl alkylation or conjugate addition by Cu catalysts, or hydrocyanation of olefins by Ni ones. Overall, the use of these ligands has led to the preparation of a wide variety of chiral building blocks with high enantiomeric excess. Therefore, phosphine-phosphites have become in an important class of ligands in asymmetric catalysis.

Highly enantioselective hydrogenation of N-aryl imines derived from acetophenones by using Ru-pybox complexes under hydrogenation or transfer hydrogenation conditions in isopropanol.

The asymmetric reduction of N-aryl imines derived from acetophenones by using Ru complexes bearing both a pybox (2,6-bis(oxazoline)pyridine) and a monodentate phosphite ligand has been described. The catalysts show good activity with a diverse range of substrates, and deliver the amine products in very high levels of enantioselectivity (up to 99 %) under both hydrogenation and transfer hydrogenation conditions in isopropanol. From deuteration studies, a very different labeling is observed under hydrogenation and transfer hydrogenation conditions, which demonstrates the different nature of the hydrogen source in both reactions.

Highly enantioselective hydrogenation of 1-alkylvinyl benzoates: a simple, nonenzymatic access to chiral 2-alkanols.

Going chiral! Highly enantioselective catalytic hydrogenations of enol esters 1 by using a Rh catalyst bearing a P-OP ligand are described (see scheme; NBD=norbornadiene). The catalytic system has a broad scope and allows the preparation of a wide range of chiral esters 2 bearing diverse alkyls or a benzyl group with high enantioselectivities. These esters can easily be converted in highly enantioenriched 2-alkanols.

Rhodium phosphine-phosphite catalysts in the hydrogenation of challenging N-(3,4-dihydronaphthalen-2-yl) amide derivatives.

The enantioselective catalytic hydrogenation of N-(3,4-dihydronaphthalen-2-yl) amides (1) with rhodium catalysts bearing phosphine-phosphite ligands 4 has been studied. A wide catalyst screening, facilitated by the modular structure of 4, has found a highly enantioselective catalyst for this reaction. This catalyst gives a 93% ee in the hydrogenation of 1a and also produces high enantioselectivities, ranging from 83 to 93% ee, in the hydrogenation of several OMe- and Br-substituted substrates. In contrast, the structurally related enol esters 2 are very reluctant to undergo hydrogenation. A coordination study of the representative enamide 1d has shown an unusual η(6)-arene coordination mode, over the typical O,C,C chelating mode for enamides, as the preferred one for this substrate in a Rh(I) complex. Deuteration reactions of 1c,d indicate a clean syn addition of deuterium to the double bond without an isotopic effect on the enantioselectivity.

Highly enantioselective imine hydrogenation catalyzed by ruthenium phosphane-phosphite diamine complexes.

Mildly does it: a highly enantioselective catalyst for the hydrogenation of N-aryl imines is described. This catalyst offers practical advantages because it operates under very mild conditions and is based on an Ru complex with a diamine as the sole chiral ligand.

Application of phosphine-phosphite ligands in the iridium catalyzed enantioselective hydrogenation of 2-methylquinoline.

The hydrogenation of 2-methylquinoline with Ir catalysts based on chiral phosphine-phosphites has been investigated. It has been observed that the reaction is very sensitive to the nature of the ligand. Optimization of the catalyst, allowed by the highly modular structure of these phosphine-phosphites, has improved the enantioselectivity of the reaction up to 73% ee. The influence of additives in this reaction has also been investigated. Contrary to the beneficial influence observed in related catalytic systems, iodine has a deleterious effect in the present case. Otherwise, aryl phosphoric acids produce a positive impact on catalyst activity without a decrease on enantioselectivity.

Rhodium diphosphite pincer complexes. Rare preferred in-plane olefin conformation in square-planar compounds.

Square-planar ethylene rhodium derivatives bearing pincer diphosphite ligands have been prepared and characterized, they display a rare in-plane coordination which, based on DFT calculations, has been mainly attributed to steric effects.

Tuning of the structures of chiral phosphane-phosphites: application to the highly enantioselective synthesis of alpha-acyloxy phosphonates by catalytic hydrogenation.

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.

Highly enantioselective hydrogenation of enol ester phosphonates catalyzed by rhodium phosphine-phosphite complexes.

Chiral phosphine-phosphites provide versatile catalysts for the highly enantioselective hydrogenation of alpha-acyloxy alpha, beta-unsaturated phosphonates.