Asymmetric synthesis hydrocarboxylation

Scheme 5. Asymmetric synthesis of profens by hydrocarboxylation of aryl olefins.

More effective regio- and enantiosclcctivc asymmetric synthesis of branched optically active free carboxylic acids via palladium-catalyzed hydrocarboxylation of alkenes is achieved in the presence of (-)-(/ )- or ( + )-(5)-2,2/-(l,r-binaphthyl)phosphoric acid23. 

The results of asymmetric hydrocarboxylation of aliphatic alkenes are compiled in Table 11 and rarely exceed 20% ee. Thus, with the catalytic systems used up to now, this method is not yet conveniently applicable to the asymmetric synthesis of carboxylic acids. The new catalytic systems used for hydrocarboxylation of styrenes and heterofuuctionalized alkenes may give better results, if applied to these substrates. 

The hydroesteriflcation and hydrocarboxylation reactions catalyzed by transition metals and their complexes demonstrate the versatility of these processes. Palladium complexes are particularly useful catalysts for these reactions. Indeed, the hydrocarbonylation of a large variety of substrates has been selectively achieved by using palladium catalysts in homogeneous, heterogeneous, or biphasic systems. The results obtained for the thiocar-bonylation showed excellent regio- and stereoselectivity control for most substrates. It is anticipated that the prochiral nature of most of the reactants and products will open a new venue for the asymmetric synthesis of acids, esters, and thioesters of substantial development in the future. 

Alper H, Hamel N. Asymmetric-synthesis of acids by the palladium-catalyzed hydrocarboxylation of olefins in the presence of (R)-(—)-l,l -binaphthyl-2,2 -diyl or (S)-(- -)-l,l -binaphthyl-2, 2 -diyl hydrogen phosphate. J. Am. Chem. Soc. 1990 112 2803-2804. 

Since the discovery and development of highly efficient Rh catalysts with chiral diphosphites and phosphine-phosphites in the 1990s, the enantioselectivity of asymmetric hydroformylation has reached the equivalent level to that of asymmetric hydrogenation for several substrates. Nevertheless, there still exist substrates that require even further development of more efficient chiral ligands, catalyst systems, and reaction conditions. Diastereoselective hydroformylation is expected to find many applications in the total synthesis of complex natural products as well as the syntheses of biologically active compounds of medicinal and agrochemical interests in the near future. Advances in asymmetric hydrocarboxylation has been much slower than that of asymmetric hydroformylation in spite of its high potential in the syntheses of fine chemicals. 

In spite of its potential apphcability in fine chemical synthesis, asymmetric hydrocarboxylation seems to be waiting for a conceptual improvement to meet practical interests. 

Only recently have better results for asymmetric hydrocarboxylation and interesting applications to stereoselective organic synthesis been achieved. Earlier results are extensively reviewed together with other catalytic methods7-13 39-4,1. As in asymmetric hydroformylation a simple model can be applied to predict the prevailing antipode and regioisomer in the reaction products of asymmetric hydrocarboxylation12. 

Asymmetric hydrocarboxylation may be applied to the synthesis of chiral A -protected amino carboxylic acids, pyrrolidones or proline precursors. With this synthetic target in mind hydrocarboxylation of/f-substituted A -vinyl- and A -allylphthalimides is catalyzed with palla-dium(ll) chloride in the presence of the chiral phosphanes Diop or DIOCOL28. Although high product selectivities and regioselectivities are achieved, only very low asymmetric inductions are observed (up to 4% ee)28. Until now the best results in a vinyl imide hydrocarboxylation are achieved with, V-vinylsuccinimide in the presence of palladium(II) chloride and (-)-Diop with a 17.1 % ee12. 

Although no experimental details have been reported as yet, these results offer new, interesting applications of asymmetric hydrocarboxylation in the stereoselective synthesis of chiral hetero-functionalized carboxylic acids. 

Becker Y, Eisenstadt A, Stille JK. Asymmetric hydro-formylation and hydrocarboxylation of enamides-synthesis of alanine and proUne. 7. Org. Chem. 1980 45 2145-2151. 

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