Alkenes dihydroxylation, catalytic

Although a large number of asymmetric catalytic reactions with impressive catalytic activities and enantioselectivities have been reported, the mechanistic details at a molecular level have been firmly established for only a few. Asymmetric isomerization, hydrogenation, epoxidation, and alkene dihydroxylation are some of the reactions where the proposed catalytic cycles could be backed with kinetic, spectroscopic, and other evidence. In all these systems kinetic factors are responsible for the observed enantioselectivities. In other words, the rate of formation of one of the enantiomers of the organic product is much faster than that of its mirror image. 

Figure 9.10 Catalytic cycle for Os04-catalyzed asymmetric alkene dihydroxylation. The dashed line represents the phase boundary between the organic and the aqueous phase. L is the chiral ligand, e.g., 9.44.

Quite recently it was reported that in addition to hydrogen peroxide, periodate or hexacyanoferrat(III), molecular oxygen21,31-34 can be used to reoxidize these metal-oxo compounds. New chiral centers in the products can be created with high enantioselectivity in the dihydroxylation reactions of prochiral alkenes. The development of the catalytic asymmetric version of the alkene dihydroxylation was recognized by Sharpless receipt of the 2001 Nobel prize in Chemistry. 

The catalytic cycle for 0s04-catalyzed alkene dihydroxylation in the presence of the cooxidant NMO is shown in Scheme 7.25. 

Some very widely used organic reactions are catalyzed or mediated by transition metals. For example, catalytic hydrogenation of alkenes, dihydroxylation of alkenes, and the Pauson-Khand reaction require Pd, Os, and Co complexes, respectively. The d orbitals of the transition metals allow the metals to undergo all sorts of reactions that have no equivalents among main-group elements. This doesn t mean that the mechanisms of transition-metal-mediated reactions are difficult to understand. In fact, in some ways they are easier to understand than standard organic reactions. A transition-metal-catalyzed or -mediated reaction is identified by the presence of a transition metal in the reaction mixture. 

Dihydroxylation. Besides the enormously popular and effective cinchona alkaloid-based chiral auxiliaries several C2-symmetrical diamines (13), (14) and (15) have been developed to direct alkene dihydroxylation with OSO4. These efforts are probably overwhelmed by the Sharpless protocols because the approaches are not catalytic with respect to the most expensive and toxic reagent. 

Catalytic asymmetric dihydroxylation of alkenes with participation of insoluble polymer-bound cinchonine alkaloids 99SLI181. 

Syn-Dihydroxylation. When the reaction was first discovered, the syn-dihydroxylation of alkenes was carried out by using a stoichiometric amount of osmium tetroxide in dry organic solvent.56 Hoffman made the observation that alkenes could react with chlorate salts as the primary oxidants together with a catalytic quantity of osmium tetroxide, yielding syn-vicinal diols (Eq. 3.11). This catalytic reaction is usually carried out in an aqueous and tetrahydrofuran solvent mixture, and silver or barium chlorate generally give better yields.57... 

The history of asymmetric dihydroxylation51 dates back 1912 when Hoffmann showed, for the first time, that osmium tetroxide could be used catalytically in the presence of a secondary oxygen donor such as sodium or potassium chlorate for the cA-dihydroxylation of olefins.52 About 30 years later, Criegee et al.53 discovered a dramatic rate enhancement in the osmylation of alkene induced by tertiary amines, and this finding paved the way for asymmetric dihydroxylation of olefins. 

In summary, the reaction of osmium tetroxide with alkenes is a reliable and selective transformation. Chiral diamines and cinchona alkakoid are most frequently used as chiral auxiliaries. Complexes derived from osmium tetroxide with diamines do not undergo catalytic turnover, whereas dihydroquinidine and dihydroquinine derivatives have been found to be very effective catalysts for the oxidation of a variety of alkenes. OsC>4 can be used catalytically in the presence of a secondary oxygen donor (e.g., H202, TBHP, A -methylmorpholine-/V-oxide, sodium periodate, 02, sodium hypochlorite, potassium ferricyanide). Furthermore, a remarkable rate enhancement occurs with the addition of a nucleophilic ligand such as pyridine or a tertiary amine. Table 4-11 lists the preferred chiral ligands for the dihydroxylation of a variety of olefins.61 Table 4-12 lists the recommended ligands for each class of olefins. 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

In the case of prochiral alkenes the dihydroxylation reaction creates new chiral centers in the products and the development of the asymmetric version of the reaction by Sharpless was one of the very important accomplishments of the last years. He received the Nobel Price in Chemistry 2001 for the development of catalytic oxidation reactions to alkenes. 

Sharpless stoichiometric asymmetric dihydroxylation of alkenes (AD) was converted into a catalytic reaction several years later when it was combined with the procedure of Upjohn involving reoxidation of the metal catalyst with the use of N-oxides [24] (N-methylmorpholine N-oxide). Reported turnover numbers were in the order of 200 (but can be raised to 50,000) and the e.e. for /rara-stilbene exceeded 95% (after isolation 88%). When dihydriquinidine (vide infra) was used the opposite enantiomer was obtained, again showing that quinine and quinidine react like a pair of enantiomers, rather than diastereomers. 

After the "asymmetric epoxidation" of allylic alcohols at the very beginning of the 80 s, at the end of the same decade (1988) Sharpless again surprised the chemical community with a new procedure for the "asymmetric dihydroxylation" of alkenes [30]. The procedure involves the dihydroxylation of simple alkenes with N-methylmorpholine A -oxide and catalytic amounts of osmium tetroxide in acetone-water as solvent at 0 to 4 °C, in the presence of either dihydroquinine or dihydroquinidine p-chlorobenzoate (DHQ-pClBz or DHQD-pClBz) as the chiral ligands (Scheme 10.3). 

The Sbarpless asymmetric dihydroxylation of alkenes usually employs a stoichiometric amount of iodine or potassium ferricyanide to re-oxidisc the osmium centred intermediates in the catalytic cycle [73]. Either reagent can also be used in catalytic amounts and re-oxidised electrochemically at an anode [74, 75]. 

As mentioned in 1.2.1 above, there are several reviews on the properties of RuO as an oxidant in organic chemistry, both as a stoicheiometric but also as a catalytic reagent [12, 34-36, 39, 60, 64, 201-203]. It is one of the most important and versatile of Ru oxidants. In the first few years after its properties in the field were realised it was often used for oxidation of alcohol groups in carbohydrates, but its versatility as an oxidant quickly became apparent and its use was extended to a variety of other reactions, notably to alkene cleavage and, more recently, to the c/x-dihydroxylation and ketohydroxylation of alkenes. 

SCHEME 180. Catalytic cycle for the ant -dihydroxylation of alkenes using resin-supported sulfonic acid catalyst... 

Since Os04 is volatile, toxic and expensive, considerable effort has been devoted to the catalytic application of the cis dihydroxylation of alkenes in the presence of excess cooxidant.57-290 Previous procedures used metal chlorate (Hoffman reagent),339 or hydrogen peroxide (Milas reagent)350 as cooxidant, usually in Bu OH or acetone.290 Recent procedures utilize t-butyl hydroperoxide in conjunction with ammonium salts (Et4NOH or Et4NOAc)57,351 or N-methylmorpholine N-oxide,352 and are generally more selective. 

Allyl alcohols can be produced catalytically by oxidation of alkenes with TBHP in the presence of small amounts of Se02 (equation 128). In contrast to the stoichiometric reaction, this catalytic oxidation can be performed under mild conditions (r.t., CH2C12 solvent).356 Alkynic compounds undergo a predominant allylic dihydroxylation upon reaction with TBHP/CH2C12 (equation 129) 357... 

Another unexpected rearrangement was encountered in the synthesis of 1 - e/u -valiolamine, when the alkene 4 was subjected to dihydroxylation conditions. Thus, heating of a mixture of 4 with a catalytic amount of OSO4 in a water/pyridine/t-butanol mixture containing trimethylamine N-oxide under reflux for 2 days gave a mixture of 5 (29%) and the a-diol 6 (14%) together with 46% of unchanged alkene 4. 

Transformation of alkene 9 into diol 30 is a Sharpless asymmetric dihydroxylation.8 Its catalytic cycle with K3Fe(CNV, as co-oxidant is shown below. 

Chiral amino alcohols and diamines. The chiral vtc-diols available by catalytic asymmetric dihydroxylation of alkenes (14, 237-239) can be converted via a derived cyclic sulfite into chiral 1,2-amino alcohols and diamines as shown in equation I. The same transformations are useful in conversion of 1-alkyl- or arylethane-1,2-diols into the corresponding amino alcohols and diamines. 

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. 

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