Diene enantioselective dihydroxylation

Landais has extended his desymmetrization of dienes from dihydroxylation approaches to a cyclopropanation reaction. A Cu-pybox complex provides the highest enantioselectivities and good diastereoselectivity in the asymmetric cyclopropanation of the silyl-substituted cyclopentadiene 210 ... 

Excellent chemoselectivity in the enantioselective dihydroxylation of dienes has been observed with substrates such as 324 (Equation 51) and 326 (Equation 52) [218], An interesting expansion of this methodology was recently reported by Donohoe, who discovered that 1,5-dienes participated smoothly in highly diastereoselective osmium-catalyzed oxidative cyclization reactions [219]. This mild oxidation method was combined with an initial asymmetric catalytic dihydroxylation reaction to give optically active tetrahydrofurans, as illustrated by the conversion of 328 into 330 (95 % ee. Scheme 9.42) [220]. 

When asymmetric epoxidation of a diene is not feasible, an indirect route based on asymmetric dihydroxylation can be employed. The alkene is converted into the corresponding syn-diol with high enantioselectivity, and the diol is subsequently transformed into the corresponding trans-epoxide in a high-yielding one-pot procedure (Scheme 9.5) [20]. No cpirricrizalion occurs, and the procedure has successfully been applied to natural product syntheses when direct epoxidation strategies have failed [21]. Alternative methods for conversion of vicinal diols into epoxides have also been reported [22, 23]. 

This strategy can be applied to the synthesis of vinylepoxides, since high enantioselectivity and good regioselectivity can often be obtained in asymmetric dihydroxylation of dienes, resulting in vinylic diols [24, 25], Transformation of the diols into epoxides thus represents an alternative route to vinylepoxides. This strategy was recently employed in the synthesis of (+)-posticlure (Scheme 9.6) [26]. 

As an example of conversion of complex 111 to 113, optically pure complex 126 was used for the enantioselective total synthesis of shikimic acid (129) [30]. The hydroxy-substituted diene complex 127 was prepared from 126. Silylation and decomplexation of 127 gave 128. Stereoselective dihydroxylation of the more reactive double bond of the decomplexed silyl ether derivative 128, followed by desilylation afforded (—)-methyl shikimate (129). 

When applied to penta-1,4-diene, the Sharpless asymmetric dihydroxylation forms a 1 1 mixmre of (25,45)- and (25,4/ )-penta-l,2,4,5-tetrols 478 and 479, which can be converted to diepoxides 480 and 481, respectively [214] (Scheme 13.110). A stereo- and enantioselective synthesis of 480 is possible starting from l,5-dichloropenta-2,4-dione applying Noyori s asymmetric hydrogenation [215]. 

Double AD of dienes is an interesting way to enhance the enantioselectivity of the first dihydroxylation reaction. This amplification process, which has been applied to many other asymmetric reactions, usually results in significant improvement of the enantiopurity of the bis dihydroxylated product. Momose [ 140] has studied in detail the double AD of several non-conjugated dienes, during his elegant synthesis of a range of optically active nitrogen heterocycles (Scheme 62). 

In a simplified catalytic cycle, reversible coordination of the dienophile to the Lewis acid (LA) activates the substrate toward diene cycloaddition. In the catalyst turnover event, the Lewis acid-product complex dissociate to reveal the de-complexed cycloadduct and regenerated catalyst (Scheme 2). While this catalytic cycle neglects issues of product inhibition and nonproductive catalyst binding for dienophiles having more than one Lewis basic site, the gross features of this process are less convoluted than many other enantioselective reactions e.g., olefin dihydroxylation, aldol reactions), a fact which may provide insight as to why this process is frequently used as a test reaction for new Lewis acid catalysts. 

The c/s-dihydroxylation reaction catalyzed by these dioxygenases is typically highly enantioselective (often >98% ee) and, as a result, has proven particularly useful as a source of chiral synthetic intermediates (2,4). Chiral cis-dihydrodiols have been made available commercially and a practical laboratory procedure for the oxidation of chlorobenzene to IS, 2S)-3-chlorocyclohexa-3,5-diene-l,2-c diol by a mutant strain of Pseudomonas putida has been published (6). Transformation with whole cells can be achieved either by mutant strains that lack the second enzyme in the aromatic catabolic pathway, cw-dihydrodiol dehydrogenase (E.C. 1.3.1.19), or by recombinant strains expressing the cloned dioxygenase. This biocatalytic process is scalable, and has been used to synthesize polymer precursors such as 3-hydroxyphenylacetylene, an intermediate in the production of acetylene-terminated resins (7). A synthesis of polyphenylene was developed by ICI whereby ftie product of enzymatic benzene dioxygenation, c/s-cyclohexa-3,5-diene-1,2-diol, was acetylated and polymerized as shown in Scheme 2 (8). 

Dienes are interesting substrates for the dihydroxylation reaction. In cases where the diene is symmetrical the enediols are isolated in good yield and enantioselectivity. For example, diene (5.21) affords the enediol (5.24). 

The oxidative functionalization of olefins mediated by transition metal oxides leads to a variety of products including epoxides, 1,2-diols, 1,2-aminoalcohols, and 1,2-diamines [1]. Also the formation of tetrahydrofurans (THF) from 1,5-dienes has been observed, and enantioselective versions of the different reactions have been developed. Although a lot of experimental data has been available, the reaction mechanisms have been a subject of controversial discussion. Especially, osmium (VIII) complexes play an important role there, as the proposal of a stepwise mechanism [2] for the dihydroxylation (DH) of olefins by osmium tetroxide (OSO4) had started an intense discussion about the mechanism [2—11],... 

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