Chiral monodentate phosphites

The chiral monodentate phosphites presented in Scheme 28.6 are easily prepared from a diol, phosphoms trichloride, and an alcohol. Usually, the diol is converted into the corresponding phosphoro chloridite, followed by reaction... 

Chiral monodentate phosphites and phosphoramidites are also effective ligands for Rh-catalyzed asymmetric hydrogenation of enamide substrates. As seen in the structure of MonoPhos illustrated in Figure 1.2, combination of the mod-ihed BINOF backbone and the amine part gives a structural variety to this type of ligand. Combinatorial methods are effective for optimization of the chiral structures.Elucidation of the hydrogenation mechanism catalyzed by the MonoPhos-Rh complex is in progress." ... 

Monodentate phosphites are another type of prominent monodentate phosphorus ligands applied in asymmetric hydrogenation of enamides for the synthesis of chiral amines. Chiral monodentate phosphites can be easily prepared from a chiral diol and an alcohol. Generally, the chiral diol was first reacted with a phosphorus trichloride to form a phosphorochloridite, followed by the reaction with an appropriate alcohol to yield a chiral monodentate phosphite [35[. The reaction of an alcohol with phos phorus trichoride to yield a phosphorodichloridite, which was then treated with a chiral diol, is also a good procedure for the synthesis of chiral monodentate phosphites [36]. 

Reetz, M. T. Mehler G. Meiswinkel, A. Mixtures of chiral monodentate phosphites, phosphonites and phosphines as ligands in Rh-catalyzed hydrogenation of N-acyl enamines Extension of the combinatorial approach. Tetrahedron Asymmetry 2004,15,2165-2167. 

However, it is possible that the heterocatalyst becomes the dominant one, either if it is more stable and thus formed in large excess, or if it is a more active, kinetically dominant catalyst. Recently, both Reetz et al. and Feringa/Min-naard/de Vries et al. have shown that this approach can be beneficial. Earlier attempts by Chen and Xiao using mixtures of monodentate phosphites based on bisphenol and a chiral alcohol were not successful [39]. In our experience, the majority of catalysts based on mixtures of monodentate ligands show a poorer performance than the individual homo-catalysts. However, in a few instances there is a positive effect. 

Compared with the simple monophosphites, the monodentate phosphites derived from the easily available carbohydrates afforded considerably higher enantioselec tivities in the asymmetric hydrogenation of enamides. Zheng and coworkers developed a series of binaphthyl carbohydrate monodentate phosphites from D fructose and d glucose. The phosphite 29 (Scheme 8.11) exhibited a better enantioselectivity in the rhodium catalyzed asymmetric hydrogenation of arylena mides [37]. Fructose and glucose derived phosphites have several chiral centers and... 

It also has been found that chiral monodentate phosphine derivatives can be used in place of the diphosphine. Reetz et al. studied the kinetics of a Rh(I) system with chiral phosphite ligands. The rate is first-order in pressure and is optimum for a 2 1 ratio of phosphite Rh. These authors suggest that the reaction follows the olefin route, with the rate-limiting step being the oxidative addition of Hj, and that the active catalyst retains two phosphite ligands. The R configuration of the phosphite prixluces mainly the R-enantiomer from itaconic acid dimethyl ester. Calculations indicate that this comes from the major catalyst-substrate complex. 

FIGURE 29.1. Examples of chiral monodentate phosphorous-containing ligands phosphites, phos-phoramides, phosphordiamides, phosphinites, phosphonites, aminophosphonites, and aminophosphines. 

Rhodium complexes, formed in situ with [Rh(COD)2]BF4 and monodentate chiral spiro phosphite and phosphine ligands, catalyse the AH of both (Z)- and (E)-P-arylenamides with up to 97% ee. A library of 19 chiral binol-monophosphite ligands containing a phthalic acid secondary bis-amide group has been synthesized and screened for use in stereocontrol of rhodium-catalysed hydrogenation of several prochiral dehydroamino esters and enamides. Spectroscopic and computational studies... 

The use of copper catalysts based on chiral phosphorus ligands to assist 1,4-additions of dialkylzinc reagents has in recent years produced major breakthroughs, with excellent enantioselectivities. A number of monodentate and bidentate phos-phoramidites, phosphites, phosphonites, and phosphines are now available as chiral ligands for alkyl transfer to a variety of cyclic and acyclic enones. So far. 

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