Sharpless asymmetric dihydroxylation Diastereoselectivity

Moitessier, N., Maigret, B., Chretien, F., Chapleur, Y. Molecular dynamics-based models explain the unexpected diastereoselectivity of the Sharpless asymmetric dihydroxylation of allyl D-xylosides. Eur. J. Org. Chem. 2000, 995-1005. 

Scheme 50. Characterization of a Synthesis o/lOO, in Which the CJ Building Block Supplies the First Stereogenic Center. The other stereogenic centers are diastereoselectively introduced by Sharpless asymmetric dihydroxylation of the aUcenyl-substituted furan or by Zn(BH4)2 reduction of the Cjg furan cleavage product, respectively [99d]...

The enantiomerically pure 2,3-unsaturated aldonic lactone 2 was prepared following Sharpless asymmetric dihydroxylation of 2-vinylfuran to give 1 (Scheme 1). The chain-extended aldonolactones 4 and 5 were prepared from the P-keto ester 3 by use of a diastereoselective reduction with either d- or L-tartaric acid in conjuction with sodium borohydride (Scheme 2). Reaction of Meldrum s acid (5a) with D-aldopentoses and hexoses gave 3,6-anhydro-2-deoxy-aldono-... 

Olefin 104 was then subjected to a Sharpless asymmetric dihydroxylation which proceeded with moderate diastereoselectivity, leading to an inseparable mixture of the diols 105a and 105b (d.r. 71 29) (Scheme 29). Fortunately, when the mixture of 105a and 105b was submitted to the following three-step sequence, for example, selective protection of primary alcohol, mesylation, and then cyclization, the major isomer 106a could be isolated in pure form. Two further deprotection steps were necessary to provide the hyacinthacine Bi 3 in 45.5% overall yield and 13 steps from lactam 101. In paraUel,... 

Sharpless asymmetric dihydroxylation of 24 with AD-mix a or fi did not improve the diastereoselectivity. 

Next, dihydroxylation of homoaUyl alcohol 2.201 was examined for the installation of the stereoselective epoxide (Scheme 2.42). The hydroxyl in 2.201 was protected as the methyl ether 2.202, which was subsequently subjected to Sharpless asymmetric dihydroxylation reaction [149] conditions to afford 2.203, however, no diastereoselectivity was observed and the reaction resulted in the oxidation of the dithiane group under such oxidation reaction conditions. 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

Stilbene diols such as 3 are gaining prominence both as synthetic intermediates and as effective chiral auxiliaries. While the diols can be prepared in high by Sharpless dihydroxylation, it would be even more practical to prepare them by direct asymmetric pinacol coupling. N. N. Joshi of the National Chemical Laboratory in Pune reports (J. Org. Chem. 68 5668,2003) that 10 mol % of the inexpensive Ti salen complex 2 is sufficient to effect highly enantioselective and diastereoselective pinacol coupling of a variety of aromatic aldehydes. Most of the product diols are brought to >99% by a single recrystallization. 

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