Bisphosphine catalysts

A class of chiral bisphosphines based on 3,4-bis(diphenylphosphino)pyrrolidines (9) has been developed by Degussa and the University of Munich. Rhodium-bisphosphine catalysts of this class can reduce a variety of enamides to chiral amino acid precursors with high enantioselectivities. These catalysts are extremely rapid and can operate with high S/C ratios (10,000-50,000) under moderately high hydrogen pressure (150-750 psig). Contrary to other rhodium catalysts that contain... 

Takasago has patented an alternate route to /-menthol (22) (Scheme 12.36).131 Chirality is set by the rhodium catalyzed asymmetric hydrogenation of piperitenone (108). Although many chiral biaryl bisphosphines catalysts have been used, DTMB-SegPHOS (107c) produced pulegone (109) in 90% yield and 98% ee with an S/C ratio of 50,000.131... 

The next quantum leap in catalysis after DuPhos has been the development of the ruthe-nium-diamine-bisphosphine catalysts (JST). This combination of ligands on ruthenium produces a highly active and enantioselective catalyst for the reduction of aryl ketones at mild conditions. Although this technology is relatively young, the potential is strong for many industrial processes that use this catalyst system. 

An additional problem that has been partially overcome with the newer catalysts is the control of the E Z stereochemistry of the resulting products. For example, in the synthesis of epotholone, the Danischefsky group examined the stereochemistry as a function of the substituents around the ring [24]. With Ru-2, the Z stereochemistry of the product was found to be controlled by subtle conformational changes induced by substituents. That the Ru-2 and other bisphosphine catalysts gave the kinetically controlled product was demonstrated in a simple system (Figure 6.9). 

The bisphosphine catalyst Ru-2 would react only slowly with electron-defident olefins in RCM reactions. As shown below, the reaction between a terminal olefin and an acrylate using Ru-2 gave none of the cross product. With the more electron-donating ligand in Ru-4, the same reaction gave the substituted acrylate as the major product [40]. 

Two factors contribute to the success of this reaction the outstanding enantio-selectivity achieved, and efficiency of the catalyst (i.e, high turnover). The above analysis emphasizes only the former, but the latter also varies with the nature of the chiral bisphosphine ligand and the structure of the substrate. The structural features of the substrate and the catalyst are mutually optimal in the example cited above. Perturbation of any of these features usually lowers either the enantioselectivity or the turnover rate. The range of substrates that are amenable to asymmetric hydrogenation with this catalyst system is, therefore, limited. Figure 7.9 illustrates the classes of substrate that can be accomodated by cationic rhodium bisphosphine catalysts [104]. For a more extensive summary, see ref. [110]. 

In 2008, Hamada and colleagues employed homogeneous chiral nickel-bisphosphine catalysts for DKR. Indeed, hydrogenations through DKR of a series of a-amino-jS-ketoester hydrochlorides into the corresponding anti )S-hydroxy-a-amino esters were achieved using a combination of nickel acetate... 

Selke, R., Holz, J. and Riepe, A., Impressive enhancement of the enantioselectivity for a hydroxy-containing rhodium(I) bisphosphine catalyst in aqueous solution by micelle-forming amphiphiles, Chem. Eur. J., 1998, 4, 769, and references cited therein. For a recent application, see Grassert, I., Schmidt, U., Ziegler, S., Fischer, C. and Oehme, G., Use of rhodium complexes with amphiphilic and nonamphiphilic Ugands for the preparation of chiral of-aminophosphonic acid esters by hydrogenation in micellar media. Tetrahedron Asymmetry, 1998, 9, 4193. 

A method for the asymmetric hydrogenation of seven-membered cyclic imines of benzodiazepinones and benzodiazepines has recently been published. The chiral cyclic amines generated from these reactions make up the cores of many natural products and clinical drugs. Iridium-bisphosphine catalyst systems were investigated and found to give promising enantios-electivities which could be improved upon addition of morpholine tri-fluoroacetate. The optimum conditions, applied to model compound 50, are shown in Scheme 14.19, giving 51 in excellent enantioselectivity and complete conversion. 

As far as the oxidative addition is concerned, two different mechanisms are proposed for this step a concerted mechanism and a nucleophihc attack mechanism. Calculations on the concerted mechanism show that the size of the phosphine does not significantly affect this process for monophosphine catalytic systems. In fact, it is experimentally shown that the rate constants for the oxidative addition depend more on the identity of the halide of the ArX electrophihc reactant than of the steiic bulk of the phosphine ligands. The nature of the phosphine ligand may affect this process not because of the oxidative addition elementary step itself (where the effect is rather small), but due to its own intrinsic capability of generating mono- or bisphosphine catalysts. The oxidative addition process in monophosphine systems are more favorable than in their bisphosphine counterparts. In fact, the most active phosphine ligands known are the bulky and electron-rich dialkylbiaryl phosphines developed by Buchwald s group. 

On the other hand, in the nucleophilic attack mechanism an inversion of configuration on the organic reaction was observed. For the particular case of sp carbon atoms in a-sulfoxide systems the mechanism was proposed to be rather similar for both the mono- or bisphosphine catalysts. 

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