Sharpless-type ligands

The asymmetric epoxidation of functionalized alkenes still attracts considerable attention. Synthetic chemists continue to be in search of new and improved routes to epoxides, since they provide versatile intermediates for natural product synthesis. The topic of preparative techniques for chiral epoxides is seldom broached without the mention of the Sharpless epoxidation. Indeed, the impact of this protocol cannot be overestimated, as new applications continue to be reported. For example, linear poly(tartrate ester) ligands have been used this past year to generate a solid-supported Sharpless-type catalyst <97CC123>. 

A novel Sharpless-type asymmetric dihydroxylation ligand with a triazine core 285 was prepared by Bradley and co-workers in two, easy, high-yielding steps from readily available starting materials, and offered an economic alternative to other systems (Scheme 51). The catalyst was found to be active in the asymmetric dihydroxylation of alkenes, especially those of /ra r-geometry. 

Also fifteen years of painstaking work and the gradual improvement of the system, the Sharpless team announced that asymmetric dihydroxylation (AD) of nearly every type of alkene can be accomplished using osmium tetraoxide, a co-oxidant such as potassium ferricyanide, the crucial chiral ligand based on a dihydroquinidine (DHQD) (21) or dihydroquinine (DHQ) (22) and metha-nesulfonamide to increase the rate of hydrolysis of intermediate osmate esters 1811. 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

Recently a new ligand was introduced for terminal olefins with branching on the pendant substituent (Crispino, G. Jeong, K.-S. Kolb, H. C. Wang, Z.-M. Xu, D. Sharpless, K. B. J. Org. Chem. 1993, 58, 3785), but the phenanthryl ether ligand is on rare occasions still the best ligand for certain types of terminal olefins (the present acrolein acetal substrate is such a case). 

Figure 8.5. Ligands for the Sharpless AD process, (a) The phthalazine ligand (PHAL class), recommended for most substitution types [74,75]. (b) The diphenylpyrimidine ligand (PYR class), used for mono- and tetrasubstituted olefins...

In the presence of a chiral amine such as quinine, Sharpless has demonstrated asymmetric catalysis for this dihydroxylation reaction that is also accelerated by this type of ligand. The oxidizing agent (oxygen donor) is then amine oxide. This system compares with Jacobsen s efficient hydrolytic kinetic resolution shown in section 4, but extension to the industrial scale is more problematic with the Sharpless system. 

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