Chiral phosphines, synthesis

Borane complexes of P-heterocycles as versatile precursors for the synthesis of chiral phosphine ligands used for asymmetric catalysis 98S1391. 

A similar situation occurs in trivalent phosphorus compounds, or phosphines. It turns out, though, that inversion at phosphorus is substantially slower than Inversion at nitrogen, so stable chiral phosphines can be isolated. (R)- and (5)-metbylpropylphenylphosphine, for example, are configurationally stable for several hours at 100 °C. We ll see the Importance of phosphine chirality in Section 26.7 in connection with the synthesis of chiral amino adds. 

Table 3.12 surveys current industrial applications of enantioselective homogeneous catalysis in fine chemicals production. Most chiral catalyst in Table 3.12 have chiral phosphine ligands (see Fig. 3.54). The DIP AMP ligand, which is used in the production of L-Dopa, one of the first chiral syntheses, possesses phosphorus chirality, (see also Section 4.5.8.1) A number of commercial processes use the BINAP ligand, which has axial chirality. The PNNP ligand, on the other hand, has its chirality centred on the a-phenethyl groups two atoms removed from the phosphorus atoms, which bind to the rhodium ion. Nevertheless, good enantio.selectivity is obtained with this catalyst in the synthesis of L-phenylalanine. 

In order to prepare a new range of ligands incorporating both sulfoximine and phosphine moieties, Tye et al. reported, in 2001, the synthesis of a novel chiral phosphine-sulfoximine, which was tested as a ligand in the copper-catalysed 1,4-addition of ZnEt2 to enones. Whilst the reaction of acyclic enones gave the corresponding racemic 1,4-products, the best result was obtained upon... 

Chiral phosphine based transition metal complexes are nsed as a powerful tool for asymmetric synthesis (3). A fundamental mechanistic nnderstanding is required for rhodium and mthenium catalyzed reactions. The starting point of those investigations was the clear and detailed stractnral description of the isolated pre catalyst system. 

Kovacik, I., Wicht, D.K., Grewal, N.S., Glueck, D.S., Incarvito, C.D., Guzei, I.A., and Rheingold, A.L., Pt(Me-Duphos)-catalyzed asymmetric hydrophosphination of activated olefins enantioselective synthesis of chiral phosphines,... 

Enantioselective hydrogenation of simple ketones catalyzed by BINAP/chiral diamine-Ru complexes is applied to the synthesis of biologically active compounds and a chiral phosphine ligand. Some examples are shown in Figure 32.44 [85 a, 87, 102, 128, 130, 135],... 

Much effort has been devoted to investigating chiral phosphine ligands for their synthesis and asymmetric catalytic hydrogenation potential, and such chiral phosphine ligands have been extensively used for catalytic asymmetric hydrogenation, both academically and industrially.14... 

A synthesis of novel chiral phosphine oxide aminal 113 has been developed by reacting phosphine oxide aldehyde 111 with diamine 112. The condensation gave a single diastereomer of the phosphine oxide aminal in 65% yield. This compound can be used as chiral auxiliary in asymmetric synthesis (Equation 15) <1996TA3431, 1996TL3051, 1996TL7465>. 

In 2001, a palladium-catalyzed asymmetric hydrosilylation of 4-substituted-but-l-en-3-ynes (146) was reported by Hayashi and co-workers [115]. It was found that a monodentate bulky chiral phosphine, (S)-(R)-bisPPFOMe, was effective for the asymmetric synthesis of the axially chiral allenes 147 and up to 90% ee was achieved (Scheme 3.75). The bulky substituent at the 4-position in 146 is essential for the selective formation of the allene 147 the reaction of nC6H13C=CCH=CH2 gave a complex mixture of hydrosilylation products which consisted of <20% of the allenylsilane. 

Addition of Hydrogen Phosphinates and Extension to Synthesis of P-Chiral Phosphinates. 50... 

A ferrocenyloxazoline with only one adjacent position available for deprotonation will lithiate at that position irrespective of stereochemistry. This means that the same oxazoline can be used to form ferrocenes with either sense of planar chirality. The synthesis of the diastereoisomeric ligands 311 and 313 illustrates the strategy (Scheme 143), which is now commonly used with other substrates to control planar chirality by lithiation (see below). Ferrocene 311 is available by lithiation of 305 directly, but diastereoselective silylation followed by a second lithiation (best carried out in situ in a single pot) gives the diastereoisomeric phosphine 313 after deprotection by protodesilylation ". ... 

The reduction of double bonds using chiral phosphine ligands as the precursors for the appropriate catalysts is a widely used strategy in the asymmetric synthesis of... 

Gilbertson. S.R. and Wang. X. (1999) The parallel synthesis of peptide based phosphine ligands. Tetrahedron, 55. 11609-11618 Gilbertson. S.R. and Wang. X. (1995) The combinatorial synthesis of chiral phosphine ligands. Tetrahedron Lett.. 37. 6475-6478. 

Gilbertson, S. R. Wang, X. The Combinatorial Synthesis of Chiral Phosphine Ligands, Tetrahedron Lett. 1996, 37, 6475. 

Synthesis of a New Chiral Phosphine and Its Application to Asymmetric Catalysis... 

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