Organic Sharpless dihydroxylation

The Sharpless dihydroxylation reaction (AD) is arguably the most important discovery in organic chemistry of the 20th century. There is no question that asymmetric synthesis is at the forefront of modern synthetic organic chemistry. And the most impressive asymmetric methods are those which are catalytic. The Sharpless epoxidation achieved this and more. But those methods that... 

The osmium-catalyzed dihydroxylation reaction, that is, the addition of osmium tetr-oxide to alkenes producing a vicinal diol, is one of the most selective and reliable of organic transformations. Work by Sharpless, Fokin, and coworkers has revealed that electron-deficient alkenes can be converted to the corresponding diols much more efficiently when the pH of the reaction medium is maintained on the acidic side [199]. One of the most useful additives in this context has proved to be citric acid (2 equivalents), which, in combination with 4-methylmorpholine N-oxide (NMO) as a reoxidant for osmium(VI) and potassium osmate [K20s02(0H)4] (0.2 mol%) as a stable, non-volatile substitute for osmium tetroxide, allows the conversion of many olefinic substrates to their corresponding diols at ambient temperatures. In specific cases, such as with extremely electron-deficient alkenes (Scheme 6.96), the reaction has to be carried out under microwave irradiation at 120 °C, to produce in the illustrated case an 81% isolated yield of the pure diol [199]. 

The asymmetric dihydroxylation protocol was the second massive contribution by Professor Barry Sharpless to synthetic organic chemistry. The first procedure, introduced with Katsuki, involves the catalytic asymmetric epoxida-tion of allylic alcohols. A typical example is shown in Scheme 17, wherein ( )-allylic alcohol (23) is epoxidized with tert-b utyl hyd roperox ide, in the presence of titanium tetra-isopropoxide and optically active diethyl tartrate to give the... 

The Sharpless asymmetric dihydroxylation has played a prominent role in enantioselecitve organic synthesis. Two groups have recently reported improvements in the procedure. Osmo E.O. Horni of the University of Oulu, Finland has found (J. Org. Chem. 2004,69,4816) that sodium chlorite is a more efficient reoxidant than is the usual K,[Fe(CN)J. Carlos A.M. Alfonso of the Instituto Superior , Lisbon has reported (J. Org. Chem. 2004,69,4381) that the asymmetric dihydroxylation can... 

The enantioselective oxygenation procedures, epoxidation and dihydroxylation, developed by Barry Sharpless have dominated single-enantiomer organic synthesis. Recently, several additional methods for enantioselective oxidation have been developed, based on the a-functionalization of carbonyl compounds. 

Corey also pointed out that 16 reflects the transition-state of an enzyme-substrate complex. Its formation was later supported by the observation of Michaelis-Menten-type kinetics in dihydroxylation reactions and in competitive inhibition studies [37], This kinetic behavior was held responsible for the non-linearity in the Eyring diagrams, which would otherwise be inconsistent with a concerted mechanism. Contrary, Sharpless stated that the observed Michaelis-Menten behavior in the catalytic AD would result from a step other than osmylation. Kinetic studies on the stoichiometric AD of styrene under conditions that replicate the organic phase of the catalytic AD had revealed that the rate expression was clearly first-order in substrate over a wide range of concentrations [38],... 

Osmium-catalysed dihydroxylation of olefins is a powerful route towards enantioselective introduction of chiral centers into organic substrates [82]. Its importance is remarkable because of its common use in organic and natural product synthesis, due to its ability to introduce two vicinal functional groups into hydrocarbons with no functional groups [83]. Prof. Sharpless received the 2001 Nobel Prize in chemistry for his development of asymmetric catalytic oxidation reactions of alkenes, including his outstanding achievements in the osmium asymmetric dihydroxylation of olefins. 

Unlike epoxides, these five-membered heterocyclics have received scant attention from organic chemists. But the recent catalytic asymmetric dihydroxylation of alkenes (14, 237-239), which is now widely applicable (this volume), and the ready access to optically active natural 1,2-diols has led to study of these compounds, including a convenient method for synthesis. They are now generally available by reaction of a 1,2-diol with thionyl chloride to form a cyclic sulfite of a 1,2-diol, which is then oxidized in the same flask by the Sharpless catalytic Ru04 system, as shown in equation I.1... 

Kolb HC, Sharpless KB (1998) Asymmetric dihydroxylation. In Beller M, Bolm C (eds) Transition metals in organic synthesis. Wiley-VCH. Weinheim, New York, p 220... 

The Sharpless asymmetric dihydroxylation works best for tram disubstituted alkenes, while the Jacobsen epoxidation works best for cis disubstituted alkenes. Even in this small area, there is a need for better and more general methods. Organic chemistry has a long way to go. 

Kolb, H. C., Sharpless, K. B. Asymmetric dihydroxylation. Transition Metals for Organic Synthesis 1998, 2, 219-242. 

Since its discovery by Sharpless and coworkers, catalytic asymmetric dihydroxylation (AD) has significantly enhanced the utility of osmium-catalyzed dihydroxylation (Scheme 1.1) [7]. Numerous applications in organic synthesis have appeared in recent years [8]. 

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