Asymmetric osmium catalyst

Figand acceleration (the so-called Criegee effect) is the important feature of asymmetric dihydroxylation using cinchona ligands.193 In particular, bis-cinchona ligands provide remarkable acceleration (Scheme 48). This enables high turnover rates of the osmium catalysts. 

The first heterogeneous osmium catalyst applicable for asymmetric dihydroxylation reactions was described by Kobayashi and coworkers (Table 9, entry 1) [38, 39]. Osmium tetroxide was enveloped in a polymer capsule by microencapsulation techniques [40,41]. The asymmetric dihydroxylation of transmethylstyrene with poly(acrylonitrile-co-butadiene-co-styrene) microencapsulated (ABS-MC) osmium tetroxide as catalyst, NMO as the cooxidant, and (DHQD)2PHAL as the chiral ligand completed in 88% yield with 94% ee [38]. The catalyst and the chiral ligand were reused in five consecutive runs without loss of activity. However, the use of NMO as cooxidant required the slow... 

Table 9 Comparison of the asymmetric dihydroxylation ((DHQD)2PHAL) with different heterogeneous osmium catalysts...

It is probably in asymmetric dihydroxylation, where the use of ionic liquids appears to be most promising. The decreased acute toxicity of osmium tetroxide due to its suppressed volatility certainly represents a great benefit for those who work with this reagent and its derivatives. Furthermore, high cost of both the osmium catalyst, as well as the chiral ligand, make recycling of the catalyst-ionic liquid particularly attractive. On the other hand, disposal of osmium-contaminated ionic liquids in an environmentally benign manner has yet to be addressed. 

Sharpless and co-workers first reported the aminohydroxyIation of alkenes in 1975 and have subsequently extended the reaction into an efficient one-step catalytic asymmetric aminohydroxylation. This reaction uses an osmium catalyst [K20s02(OH)4], chloramine salt (such as chloramine T see Chapter 7, section 7.6) as the oxidant and cinchona alkaloid 1.71 or 1.72 as the chiral ligand. For example, asymmetric aminohydroxylation of styrene (1.73) could produce two regioisomeric amino alcohols 1.74 and 1.75. Using Sharpless asymmetric aminohydroxylation, (IR)-N-ethoxycarbonyl-l-phenyl-2-hydroxyethylamine (1.74) was obtained by O Brien et al as the major product and with high enantiomeric excess than its regioisomeric counterpart (R)-N-ethoxycarbonyl-2-phenyl-2-hydroxyethylamine (1.75). The corresponding free amino alcohols were obtained by deprotection of ethyl carbamate (urethane) derivatives. 

Kobayashi S, Sugiura M. Immobilization of osmium catalysts for asymmetric dihydroxylation of olefins. Adv. Synth. Catal. 2006 348 1496-1504. 

The discovery of iron complexes that can catalyze olefin czs-dihydroxylation led Que and coworkers to explore the possibility of developing asymmetric dihydroxylation catalysts. Toward this end, the optically active variants of complexes 11 [(1R,2R)-BPMCN] and 14 [(1S,2S)- and (lP-2P)-6-Me2BPMCN] were synthesized [35]. In the oxidation of frans-2-heptene under conditions of limiting oxidant, 1R,2R-11 was foimd to catalyze the formation of only a minimal amount of diol with a slight enantiomeric excess (ee) of 29%. However, 1P-2P-14 and 1S,2S-14 favored the formation of diol (epoxide/diol = 1 3.5) with ees of 80%. These first examples of iron-catalyzed asymmetric ds-dihydroxylation demonstrate the possibility of developing iron-based asymmetric catalysts that may be used as alternatives to currently used osmium-based chemistry [45]. 

Table 7.20 Mass of extracted product, yield, ee-values and osmium content for recycling experiments of osmium catalyst for asymmetric dihydroxylation.

The asymmetric dihydroxylation of alkenes (the AD reaction) using osmium catalysts was discovered and developed by Sharpless, and now represents one of the most impressive achievements of asymmetric catalysis. The majority of early results did not use catalytic systems however, a breakthrough in the catalytic asymmetric dihydroxylation reaction was reported by Sharpless and coworkers in 1988. 

In 2009, Donohoe et al. reported a total synthesis of the natural products (-l-)-ds-sylvaticin 19 and (-l-)-sylvaticin 20 using a Sharpless asymmetric dihydroxylation of diene 15 with an osmium catalyst as key step to give the diol 16. This was followed by an oxidative cychzation to yield the functionalized tetrahydrofuran (THF) 18 stereoselectively through the cychc intermediate 17 (Scheme 9.4) [10]. 

This catalytic system allows three independent transformations to occur in sequence the Heck reaction, N-oxidation and asymmetric dihydroxylation (AD). The mechanism of the Heck reaction is discussed in the previous section. Here we take a closer look at the last two steps. They are coupled processes, based on the Sharpless asymmetric dihydroxylation reaction [22, 23]. Several recent reviews on Sharpless asymmetric dihydroxylation cover the general synthetic aspects [24-27], together with methods for immobilization of the osmium catalysts [28]. 

With this reaction, two new asymmetric centers can be generated in one step from an achiral precursor in moderate to good enantiomeric purity by using a chiral catalyst for oxidation. The Sharpless dihydroxylation has been developed from the earlier y -dihydroxylation of alkenes with osmium tetroxide, which usually led to a racemic mixture. 

The actual catalyst is a complex formed from osmium tetroxide and a chiral ligand, e.g. dihydroquinine (DHQ) 9, dihydroquinidine (DHQD), Zj -dihydroqui-nine-phthalazine 10 or the respective dihydroquinidine derivative. The expensive and toxic osmium tetroxide is employed in small amounts only, together with a less expensive co-oxidant, e.g. potassium hexacyanoferrate(lll), which is used in stoichiometric quantities. The chiral ligand is also required in small amounts only. For the bench chemist, the procedure for the asymmetric fihydroxylation has been simplified with commercially available mixtures of reagents, e.g. AD-mix-a or AD-mix-/3, ° containing the appropriate cinchona alkaloid derivative ... 

Other functionalized supports that are able to serve in the asymmetric dihydroxylation of alkenes were reported by the groups of Sharpless (catalyst 25) [88], Sal-vadori (catalyst 26) [89-91] and Cmdden (catalyst 27) (Scheme 4.13) [92]. Commonly, the oxidations were carried out using K3Fe(CN)g as secondary oxidant in acetone/water or tert-butyl alcohol/water as solvents. For reasons of comparison, the dihydroxylation of trons-stilbene is depicted in Scheme 4.13. The polymeric catalysts could be reused but had to be regenerated after each experiment by treatment with small amounts of osmium tetroxide. A systematic study on the role of the polymeric support and the influence of the alkoxy or aryloxy group in the C-9 position of the immobilized cinchona alkaloids was conducted by Salvadori and coworkers [89-91]. Co-polymerization of a dihydroquinidine phthalazine derivative with hydroxyethylmethacrylate and ethylene glycol dimethacrylate afforded a functionalized polymer (26) with better swelling properties in polar solvents and hence improved performance in the dihydroxylation process [90]. 

Finally, osmium tetroxide-loaded, immobihzed DHQ-hgand system (28) disperses activity in the asymmetric aminohydroxylations of trans-cinnamate derivatives (Scheme 4.14) [95]. Here, the reagent system AcNHBr/LiOH was employed as nitrogen source. The immobihzed catalyst could entirely be removed by filtra-... 

In subsequent years many chiral ligands for osmium have been developed and their good asymmetric induction in dihydroxylation reactions has been shown. All of these methods either employ stoichiometric amounts of catalyst (0s04/chiral ligand) and therefore no peroxide as oxidant or K3Fe(CN)e as co-oxidant, and therefore will not be discussed further. 

Osmium-catalysed dihydroxylation has been reviewed with emphasis on the use of new reoxidants and recycling of the catalysts.44 Various aspects of asymmetric dihydroxylation of alkenes by osmium complexes, including the mechanism, acceleration by chiral ligands 45 and development of novel asymmetric dihydroxylation processes,46 has been reviewed. Two reviews on the recent developments in osmium-catalysed asymmetric aminohydroxylation of alkenes have appeared. Factors responsible for chemo-, enantio- and regio-selectivities have been discussed.47,48 Osmium tetraoxide oxidizes unactivated alkanes in aqueous base. Isobutane is oxidized to r-butyl alcohol, cyclohexane to a mixture of adipate and succinate, toluene to benzoate, and both ethane and propane to acetate in low yields. The data are consistent with a concerted 3 + 2 mechanism, analogous to that proposed for alkane oxidation by Ru04, and for alkene oxidations by 0s04.49... 

Osmium is unrivalled as catalyst for the asymmetric cis-dihydroxylation of olefins. However, Sato and coworkers reported that the perfluorosulfonic acid resin, Nafion (see Chapter 2) is an effective catalyst for the trans-dihydroxyla-tion of olefins with H202 [86]. The method is organic solvent-free and the catalyst can be easily recycled (see Fig. 4.33). The first step of this reaction is epoxi-dation which is probably carried out by resin-supported peroxysulfonic acid formed in situ. This is followed by acid-catalyzed epoxide-ring opening. 

The essential components of the catalyst for the asymmetric dihydroxylation process are osmium tetroxide (OSO4) and an ester of one or the other of the pseudoenantiomeiic cinchona alkaloids dihydro-quinidine (DH( D) and dihydroquinine (DHQ). An amine oxide, generally N-methylmorpholine N-oxide, serves as the oxidant for foe reaction. When an alkenic substrate is added very slowly to a... 

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