Selective Perhydroxylation of Squalene: Taming the Arithmetic Demon

Abstract

Osmium-catalyzed asymmetric dihydroxylation, which produces 1,2-diols of high enantiopurity from prochiral olefins, is an example of the synthetic catalysts that have been developed that rival enzymes in their efficiency and high enantioselectivity. Although the asymmetric dihydroxylation catalyst lacks an enzyme's ability to effectively distinguish among the subtly different olefinic sites in a polyolefin such as squalene, this very inability permits it to bring about the "exhaustive" polyhydroxylation of squalene to give a dodecahydroxy derivative. Twelve chemical and stereochemical events proceed in tandem with a remarkable average yield of 98 percent per step, giving 1 out of the 36 possible stereoisomers in (0.98)12 = 78.9 percent overall yield.

Multi-Bond Forming Processes in Efficient Synthesis

“…Sharpless and coworkers' six-fold dihydroxylation of squalene from 1993 is a landmark example of the enantiopurity amplification that results from a reagentcontrolled, multi-bond forming reaction. [177][178][179] The breathtakingly short approaches to polyether natural products (þ)-omaezakianol (Scheme 5) [64] and glabrescol [180] by Corey and coworkers feature stereoselective five-and four-fold epoxidations, respectively. Paterson et al's synthesis of the DEF tricyclic spiroketal fragment of spirastrellolide A (Scheme 29) [181] is another example of ingenious synthetic design using independent reactions combined with domino sequences.…”

Direct selection of antibodies that coordinate metals from semisynthetic combinatorial libraries.

“…Indeed, about one-third of nature's enzymes utilize metals in structural or catalytic roles (1). In the realm of organic synthesis, metal-catalyzed reactions are among the only reactions that compete with enzymes in efficiency and ability to control the stereochemical outcome of organic transformations (2,3). Thus, the incorporation of metal-binding sites into proteins is a step toward construction of metalloenzymes.…”

An Electrophilic Cleavage Procedure for the Asymmetric Dihydroxylation: Direct Enantioselective Synthesis of Cyclic Boronic Esters from Olefins

“…This result matches earlier elegant work from Sharpless on per-dihydroxylation of polyalkenes. [15] In addition, the stereochemistry of the second step of oxidation is consistent with the Kishi rules on dihydroxylation of cyclic allylic ethers and esters. [16] Substituted aryl boronic acids are compatible with this new AD protocol (Scheme 4, Table 2).…”