Phosphine ligands, chiral tertiary

The use of chiral tertiary phosphine ligands has been studied most widely, but other chiral ligands such as carboxylic acids (15), imines (8,16), amides (17), amines (18), alkoxides (19), and hydroxammates (13) have been investigated, and we reported recently on some sulfoxide systems (29, 21). 

Two kinds of chiral tertiary phosphine ligands have been used in asymmetric hydrogenation experiments involving rhodium complexes the Horner and Monsanto groups have concentrated on ligands whose chirality is centered at an asymmetric phosphorus atom, and the New Hampshire and Paris groups have focused their attention mainly on phosphides that carry chiral carbon moieties. 

The development of the catalytic hydrogenation system based on RhCl(PPh3)3 and methods for the resolution of optical isomers of tertiary phosphines occurred around the same time (1965), and this led to the possibility of asymmetric catalytic hydrogenation of prochiral unsaturated substances with C=C, C=0, and C=N bonds using transition metal complexes with chiral phosphine ligands. Such tertiary phosphines are of three types ... 

Chiral phosphines are widely used as auxiliaries for various metal-catalyzed asymmetric reactions and can be prepared from stable phosphine-borane complexes. Secondary P-chiral phos-phine-boranes can be prepared by reductive lithiation of the corresponding tertiary phosphine-borane using LN (eq Likewise, P-chiral tertiary phosphine ligands can be produced by the reductive lithiation of phosphinite-boranes followed by alkylation, both proceeding with retention of configuration (eq 18). ... 

Morrison JD, Masler WF. Synthesis of methyl- and neomen-thyldiphenylphosphine. Epimeric, chiral, tertiary phosphine ligands for asymmetric synthesis. J. Org. Chem. 1974 i9 2y.21Q-112. 

Following Wilkinson s discovery of [RhCl(PPh3)3] as an homogeneous hydrogenation catalyst for unhindered alkenes [14b, 35], and the development of methods to prepare chiral phosphines by Mislow [36] and Horner [37], Knowles [38] and Horner [15, 39] each showed that, with the use of optically active tertiary phosphines as ligands in complexes of rhodium, the enantioselective asymmetric hydrogenation of prochiral C=C double bonds is possible (Scheme 1.8). 

During the late 1960s, Homer et al. [13] and Knowles and Sabacky [14] independently found that a chiral monodentate tertiary phosphine, in the presence of a rhodium complex, could provide enantioselective induction for a hydrogenation, although the amount of induction was small [15-20]. The chiral phosphine ligand replaced the triphenylphosphine in a Wilkinson-type catalyst [10, 21, 22]. At about this time, it was also found that [Rh(COD)2]+ or [Rh(NBD)2]+ could be used as catalyst precursors, without the need to perform ligand exchange reactions [23]. 

Using chiral phosphines as catalyst components, asymmetric induction may be expected if R R. This assumption was tested with acetophenone as substrate (R = Ph, R = Me) and two different optically active tertiary phosphines as ligands (S)-(+ )-PMePrPh and (S)-( — )-PMePh(CH2Ph). Only insignificant optical activity of the product was achieved in both cases (optical yields below 1%). High reaction temperature and/or the low coordination number of the intermediate complexes (lack of steric factors) may be the cause of this negative result. 

At about the time of Wilkinson s discovery, new schemes were developed by others for the preparation and configurational correlation of chiral phosphines (lOa-e). The combination of advances in homogeneous catalysis and chiral phosphine technology prompted research on chiral phosphine complexes. Horner et al. (11) were the first to hypothesize in print that rhodium complexes containing optically active tertiary phosphine ligands should effect the asymmetric hydrogenation of unsymmetrically substituted olefins. 

The relatively high optical purities obtained with the Rh-NMDPP system are particularly interesting from a practical viewpoint since the NMDPP ligand is prepared from an inexpensive, commercially available, chiral precursor, (-)-menthol (17). Tertiary phosphines chiral at phosphorus, on the other hand, are much less accessible and require a classic resolution step (see later discussion for details Section II. B). 

The two tertiary phosphine ligands may be replaced by a chelating ditertiary phosphine. The greatest application of the alkene route comes in asymmetric synthesis when chiral, ditertiary phosphine ligands are used. This topic is discussed... 

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