Chiral tertiary phosphine

Advances in the use of anionic stereogenic phosphorus have been interesting. Acylation of lithium o-anisylphenylphosphide with chloro-formates bearing chiral alkyl groups provided a diastereomeric mixture that could be induced to undergo an inversion at phosphorus (at relatively low temperature) to form the more favorable diastereoisomer in a crystalline lattice.186 Subsequent conversion to the quaternary phos-phonium species was followed by removal of the acyl group and isolation of the chiral tertiary phosphine as the borane derivative (Equation 3.10). 

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). 

In 1968, the first homogeneous asymmetric hydrogenation was reported independently by Homer and Knowles (8). The Wilkinson complex and related complexes modified by the incorporation of a chiral tertiary phosphine, such as P(C6H5)(n-C3H7)(CH3), catalyzed the hydrogenation of certain hydrocarbon olefins in optical yields of 3-15%. 

Wilkinson s (I) discovery that the soluble rhodium(I) phosphine complex, [Rh(PPh3)3Cl], was capable of homogeneous catalytic hydrogenation of olefins immediately set off efforts at modifying the system for asymmetric synthesis. This was made possible by the parallel development of synthetic methods for obtaining chiral tertiary phosphines by Horner (2) and Mislow (3,4, 5). Almost simultaneously, Knowles (6) and Horner (7) published their results on the reduction of atropic acid (6), itaconic acid (6), a-ethylstyrene (7) and a-methoxystyrene (7). Both used chiral methylphenyl-n-propyl-phosphine coordinated to rhodium(I) as the catalyst. The optical yields were modest, ranging from 3 to 15%. 

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. 

Homogeneous rhodium(I)-chiral tertiary phosphine catalysts have been used to hydrogenate ketones directly and to hydrosilylate ketones and imines thus accomplishing, after hydrolysis, indirect hydrogenation. 

Preparation. - Supercritical nitrous oxide has been shown to oxidise phosphines to the related phosphine oxides under mild conditions, allowing a simple isolation of products. Oxidation of precursor phosphines by hydrogen peroxide is the final step in the synthesis of the chiral functionalised phosphine oxides (219) and (220). A novel resolution procedure for the preparation of P-stereogenic phosphine oxides is afforded by the reactions of racemic chiral tertiary phosphines with an optically pure camphorsulfonyl azide, followed by separation of the diastereoisomeric phosphazenes, and acid... 

Coordination chemistry and catalytic applications of metal complexes with chiral tertiary phosphines... 

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). ... 

The racemization of chiral tertiary phosphines in many cases is an interesting route to unavailable enantiomers [15]. For example, the thermodynamically controlled pyramidal inversion of tertiary phosphines is useful synthetically. The facile acid-catalyzed racemization of secondary phosphines involves formation of an... 

The transformation of readily available enantiopure //-menthylphosphinates 2 into chiral phosphinous acid boranes 5 permits the elaboration of bulky P-stereogenic secondary phosphine boranes. Taking advantage of the synthetic potential of these compounds, abroad range of hindered P-chiral tertiary phosphine boranes 6 were prepared with excellent enantiomeric excesses [12,13]. Phosphinous acid 5 can easily be converted into one or the other enantiomer of the secondary phosphines boranes (Sp)- or (/ p)-6 by stereoselective reduction or substitution of the phosphinite borane derivatives, respectively (Scheme 4 and Table 1). 

Diastereomer (Fp)-24 is a versatile F-stereogenic building block for the preparation of chiral tertiary phosphines. Cross-coupling of (Fp)-24 with aryUialogenides and Pd(OAc)2 gives (5p)-30 in good yields, and subsequent oxidative cleavage delivers (Fp)-29 in 81% yield. Compound (Sp)-30 can be oxidized to form (Fp)-29... 

Scheme 12 Glucofuranosyl method for the synthesis of P-chiral tertiary phosphine oxides 36...

Buono developed a very effective synthesis of chiral tertiary phosphine oxide starting from oxazaphospholidines. The enantiomerically pure oxazaphospholidine (Rp)-122 was prepared from PhP(NMe2)2 and (,S)-(+)-prolinol. Subsequent treatment of 122 with a variety of acids followed by hydrolysis gave both enantiomers of tert-butylphenylphosphine oxide 4c. It was found that the acid controlled the stereochemistry of the enantiomer obtained. By using acids of high acidity or Amberlyst 15 resin, (-h)-(R)-4c was obtained with good yields and enantioselec-tivities. When acids of low acidity were used, ( )-(,S)-4c was the preferred enantiomer. For example, / -toluenesulfonic acid (PTSA) afforded (R)-4c in 88% yield and 91% ee. After a recrystaUization the optically pure compound (/ )-(-t)-4c was obtained with >99% ee (Scheme 37) [67]. 

Alkylation or arylation of silylated alkylarylphosphines 214 instead of P-H phosphines for the preparation of chiral tertiary phosphines in some cases led to an appreciable increase of enantioselectivity. For example, as reported by Toste and Bergman [133], the reaction of arylsubstituted iodides with silylphosphines 214 catalyzed by Pd(Et-FerroTANE)Cl2, in the presence of -dimethyl-W,W,Af-pro-pylene (DMPU) led to the formation of P-chiral tertiary phosphines 215 with 55-98% ee (Scheme 69). 

It is easy to predict that the basic efforts in studying the chemistiy of chiral tertiary phosphines and phosphine oxides will be concentrated in this... 

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. 

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