Chiral phosphorus

Although unsynunetrically substituted amines are chiral, the configuration is not stable because of rapid inversion at nitrogen. The activation energy for pyramidal inversion at phosphorus is much higher than at nitrogen, and many optically active phosphines have been prepared. The barrier to inversion is usually in the range of 30-3S kcal/mol so that enantiomerically pure phosphines are stable at room temperature but racemize by inversion at elevated tempeiatuies. Asymmetrically substituted tetracoordinate phosphorus compounds such as phosphonium salts and phosphine oxides are also chiral. Scheme 2.1 includes some examples of chiral phosphorus compounds. 

Valentine DJ (1984) Preparation of the enantiomers of compounds containing chiral phosphorus centers. In Morrison JD, Scott JW (eds) Asymmetric synthesis, vol 4. Academic Press, New York, chap 3... 

Chiral Phosphorus and Sulfur-Containing Compounds in Asymmetric Synthesis. 

Variation in catalyst and ligand can lead to changes in both regio- and enantio-selectivity. For example, the hydroboration of vinyl arenes such as styrene and 6-methoxy-2-vinylnaphthalene can be directed to the internal secondary borane by use of Rh(COD)2BF4 as a catalyst.166 These reactions are enantioselective in the presence of a chiral phosphorus ligand. 

Platinum complexes with chiral phosphorus ligands have been extensively used in asymmetric hydroformylation. In most cases, styrene has been used as the substrate to evaluate the efficiency of the catalyst systems. In addition, styrere was of interest as a model intermediate in the synthesis of arylpropionic acids, a family of anti-inflammatory drugs.308,309 Until 1993 the best enantio-selectivities in asymmetric hydroformylation were provided by platinum complexes, although the activities and regioselectivities were, in many cases, far from the obtained for rhodium catalysts. A report on asymmetric carbonylation was published in 1993.310 Two reviews dedicated to asymmetric hydroformylation, which appeared in 1995, include the most important studies and results on platinum-catalogued asymmetric hydroformylation.80,81 A report appeared in 1999 about hydrocarbonylation of carbon-carbon double bonds catalyzed by Ptn complexes, including a proposal for a mechanism for this process.311... 

The reaction proceeds with retention of configuration at phosphorus, as has been demonstrated in several elegant experiments using chiral phosphorus precursors.144 146-152... 

Denmark, S.E. and Miller, PC., Asymmetric [2,3]-Wittig rearrangements with chiral, phosphorus anion-stabilizing groups, Tetrahedron Lett., 37, 6631, 1995. 

To date, following significant contributions by Knowles, Kagan, Noyori, and Burk et al., thousands of efficient chiral phosphorus ligands with diverse structures have been developed for asymmetric hydrogenation, and their catalytic asymmetric hydrogenation processes have been extensively utilized in both academic research and industry. 

Applications of Chiral Phosphorus Ligands in Asymmetric Hydrogenation... 

Hydrogenation of ct-dehydroamino acid derivatives has been a typical reaction to test the efficiency of new chiral phosphorus ligands. Indeed, a number of chiral phosphorus ligands with great structural diversity are found to be effective for the Rh-catalyzed hydrogenation of a-dehydroamino acid derivatives. Since (Z)-2-(acetamido)cinnamic... 

Asymmetric hydrogenation of 3,4-hydroisoquinolines with Ir-chiral phosphorus ligand complexes has been studied. Although the highest enantioselectivity to date is obtained with a chiral titanocene catalyst,308,308a 308c chiral BCPM-Ir or BINAP-Ir complexes with additive phthalimide or F4-phthalimide have shown some good selectivity. Some examples are listed in Table 24. 

The development of chiral phosphorus ligands has made undoubtedly significant impact on the asymmetric hydrogenation. Transition metal catalysts with efficient chiral phosphorus ligands have enabled the synthesis of a variety of chiral products from prochiral olefins, ketones, and imines in a very efficient manner, and many practical hydrogenation processes have been exploited in industry for the synthesis of chiral drugs and fine chemicals. 

A remarkable number of chiral phosphorus ligands (phosphoramidites, phosphites, and phosphines with modular structures) have been introduced into the copper-catalyzed conjugate addition of R2Zn reagents, and high enantio-selectivities (>90%) are now possible for all three different classes of substrates 2-cyclohexenones and larger ring enones, 2-cyclopentenones, and acyclic enones. 

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