Sharpless synthesis

The Sharpless synthesis (Scheme 17.13) begins with the asymmetric epoxidation of cinnamyl alcohol (50) using (-l-)-di-isopropyl tartarate (DIPT) as the chiral ligand for the... 

Finally, the asymmetric arylation of 60 has also been reported, although the yields and ee s are more modest (Scheme 15) [53]. Hydrolysis of the product 61 conveniently gives the 1,3-diol 62, an intermediate in the Sharpless synthesis of fluoxetine [54]. 

Bolm C, Barry K (1988) Sharpless synthesis of a C3-symmetric phospha[2.2.2]cyclophane. Tetrahedron Eett 29 5101-5104... 

In the last fifteen years macrolides have been the major target molecules for complex stereoselective total syntheses. This choice has been made independently by R.B. Woodward and E.J. Corey in Harvard, and has been followed by many famous fellow Americans, e.g., G. Stork, K.C. Nicolaou, S. Masamune, C.H. Heathcock, and S.L. Schreiber, to name only a few. There is also no other class of compounds which is so suitable for retrosynthetic analysis and for the application of modem synthetic reactions, such as Sharpless epoxidation, Noyori hydrogenation, and stereoselective alkylation and aldol reactions. We have chosen a classical synthesis by E.J. Corey and two recent syntheses by A.R. Chamberlin and S.L. Schreiber as examples. 

Fig. 8. Use of Sharpless asymmetric epoxidation for the preparation of an intermediate in the synthesis of FK-506 (105), where represents the chiral...

By employing Sharpless epoxidation as a key step, a multistep chemical synthesis of (E)-pantolactone has also been reported (55). 

Both saturated (50) and unsaturated derivatives (51) are easily accepted by lipases and esterases. Lipase P from Amano resolves azide (52) or naphthyl (53) derivatives with good yields and excellent selectivity. PPL-catalyzed resolution of glycidyl esters (54) is of great synthetic utiUty because it provides an alternative to the Sharpless epoxidation route for the synthesis of P-blockers. The optical purity of glycidyl esters strongly depends on the stmcture of the acyl moiety the hydrolysis of propyl and butyl derivatives of epoxy alcohols results ia esters with ee > 95% (30). 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

The phenyl group became a practical protective group for carboxylic acids when Sharpless published a mild, effective one-step method for its conversion to a carboxylic acid. It has recently been used in a synthesis of the amino acid statine, where it served as a masked or carboxylic acid equivalent. ... 

The Sharpless epoxidation is one of the most important of the newer organic reactions. Although limited to allylic alcohols, it has found wide application in natural product synthesis. 

For his work on chirally catalyzed oxidation reactions, representing a major contribution to the development of catalytic asymmetric synthesis, K. B. Sharpless was awarded the Nobel Prize for chemistry in 2001. ... 

A different approach to making chiral drugs is asymmetric synthesis. An optically inactive precursor is converted to the drug by a reaction that uses a special catalyst, usually an enzyme (Chapter 11). If all goes well, the product is a single enantiomer with the desired physiological effect In 2001, William S. Knowles, Ryogi Noyori, and K. Barry Sharpless won the Nobel Prize in chemistry for work in this area. 

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