Dihydroxylation catalytic cycle

DHQD-CL or DHQ-CL) was used as the chiral auxiliary.175,176 However, the enantioselectivity observed under catalytic conditions was inferior to that observed under stoichiometric conditions. The addition of triethylammonium acetate, which increases the rate of hydrolysis of the Osvm-glycolate intermediate, improved enantioselectivity. A further improvement in enantioselectivity was brought about by the slow addition of substrates (Scheme 44).177 These results indicated that the hydrolysis of the Osvm-glycolate intermediate (57) was slow under those conditions and (57) underwent low enantioselective dihydroxylation (second cycle). Thus, Sharpless et al. proposed a mechanism of the dihydroxylation including a second cycle (Scheme 45).177 Slow addition reduces the amount of unreacted olefin in the reaction medium and suppresses the... 

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]. 

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

The catalytic cycle in the asymmetric Sharpless dihydroxylation is Discussion... 

Scheme 6D.2. Catalytic cycle for asymmetric dihydroxylation using potassium ferricyanide as cooxidant.

When the secondary reaction cycle shown in Scheme 6D.3 was discovered, it became clear that an increase in the rate of hydrolysis of trioxogly colate 10 should reduce the role played by this cycle. The addition of nucleophiles such as acetate (tetraethylammonium acetate is used) to osmylations is known to facilitate hydrolysis of osmate esters. Addition of acetate ion to catalytic ADs by using NMO as cooxidant was found to improve the enantiomeric purity for some diols, presumably as a result of accelerated osmate ester hydrolysis [16]. The subsequent change to potassium ferricyanide as cooxidant appears to result in nearly complete avoidance of the secondary cycle (see Section 4.4.2.2.), but the turnover rate of the new catalytic cycle may still depend on the rate of hydrolysis of the osmate ester 9. The addition of a sulfonamide (usually methanesulfonamide) has been found to enhance the rate of hydrolysis for osmate esters derived from 1,2-disubstituted and trisubstituted olefins [29]. However, for reasons that are not yet understood, addition of a sulfon-amide to the catalytic AD of terminal olefins (i.e., monosubstituted and 1,1-disubstituted olefins) actually slows the overall rate of the reaction. Therefore, when called for, the sulfonamide is added to the reaction at the rate of one equivalent per equivalent of olefin. This enhancement in rate of osmate hydrolysis allows most sluggish dihydroxylation reactions to be mn at 0°C rather than at room temperature [29]. 

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. 

However, since the catalytic system is homogenous, carefully adjusted reaction conditions were needed to circumvent the second nonselective catalytic cycle. Slow addition of the alkene and the hydrogen peroxide was necessary to obtain good enantioselectivities (Table 6) [13]. Recently, Backvall s group reported that the Cinchona alkaloid ligand participated in the reoxidation process and took the role of NMO in the catalytic cycle [15]. Versions of the triple catalytic system with vanadyl acetylacetonate replacing the flavin analogue [16] or m-CPBA as the terminal oxidant [17] have been developed and successfully applied to racemic dihydroxylation reactions. 

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.

The catalytic cycle for the asymmetric dihydroxylation is shown in Figure 20. The reaction is carried out in a 1/1 t-butanol/water mixture to solubilize the potassium ferricyanide/potassium carbonate used as the oxidant. The solvent mixture, normally miscible, separates into two liquid phases upon addition of the inorganic reagents. 

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

In the catalytic process, dihydroxylation of the double bond converts the Os oxidant into an Os product, which is then re-oxidized by NMO to Os. This Os " reagent can then be used for dihydroxylation once again, and the catalytic cycle continues. 

Ahrgren, L. Sutin, L., Sharpless Asymmetric Dihydroxylation on an Industrial Scale. Org. Process Res. Dev. 1997, 1, 425. See also reference 8 therein for investigations by the Sharpless group on the nonenantioselective catalytic cycle. 

In a simplified catalytic cycle, reversible coordination of the dienophile to the Lewis acid (LA) activates the substrate toward diene cycloaddition. In the catalyst turnover event, the Lewis acid-product complex dissociate to reveal the de-complexed cycloadduct and regenerated catalyst (Scheme 2). While this catalytic cycle neglects issues of product inhibition and nonproductive catalyst binding for dienophiles having more than one Lewis basic site, the gross features of this process are less convoluted than many other enantioselective reactions e.g., olefin dihydroxylation, aldol reactions), a fact which may provide insight as to why this process is frequently used as a test reaction for new Lewis acid catalysts. 

High-valent iron-oxo intermediates are commonly invoked in catalytic cycles of mononuclear iron enzymes that activate O2 to effect metabolically important oxidative transformations. Catalytic pathways of many mononuclear non-heme iron enzymes are proposed to involve high-valent iron-oxo intermediates as the active oxidizing species. Two isomeric pentadentate bispidine Fe(II) complexes (bispi-dine = 3,7 - diazabicyclo l,3,3,nonane) in the presence of H2O2 are catalytically active for the epoxidation and 1,2-dihydroxylation of cyclooctene [78, 79]. Spectral and mechanistic studies indicate that in all these cases a Fe(IV) = O intermediate is responsible for the catalytic process [80]. 

Figure 10 illustrates the use of osmium FibreCat catalysts for the cis-dihydroxylation of cyclooctene. Two FibreCat sanples (pyridine fibre "Py-OSO4" and cyclohexyl fibre "Cyclohex-Os04") and two co-oxidants (trimethyl-amine-N-oxide and 4-methylmorpholine-N-oxide) were tested for activity over 5 catalytic cycles. Between each cycle, the fibre was filtered and washed twice in 4 1 t-butanol/water. The reason for the gradual loss in activity is not currently clear, except to say that it is not due to loss of osmium fi om the fibre. This is demonstrated in Figure 11, where we plot the amount of osmium foimd in solution after each of ftie reactions shown in Figure 10. Most of the samples showed around 5 ppm Os in solution with the highest being 10 ppm. This is no more than...

Fig. 1 Catalytic cycles of the Sharpless dihydroxylation (top) and Herrmann epoxidation (bottom), simplified...

---