Dihydroxylation catalyst

Figure 5.2 The use of hollow PDMS thimbles to achieve site separation ofGrubbs catalyst and an osmium dihydroxylation catalyst [34], The solution of the Grubbs catalyst was placed on the interior of the PDMS thimble in which a metathesis reaction was then performed. After...

Bowden and co-workers demonstrated the utility of such a system in multiple cascade reactions, including the use of an otherwise incompatible combination of a Grubbs catalyst and an osmium dihydroxylation catalyst (Figure 5.2) [34],... 

The development of RuO as a aT-dihydroxylation catalyst is a relatively new and potentially important area. Until recently OsO has been the reagent of choice for this, but use of the cheaper RuO may well become competitive, though stringent reaction conditions need to be used because RuO is so much more powerful an oxidant than OsO. Reactions are much faster than for OsO, but so-called flash dihydroxylations in which low temperatures are used have been developed, and are the subject of much current research. There are several reviews including mechanistic aspects [7-9] and one on the synthesis of poly oxygenated steroids [6]. The scope and limitations of the procedure have been discussed [155, 156]. 

Bioxazolines have also been employed in the enantioselec-tive dihydroxylation of alkenes with Osmium Tetroxide The best results have been obtained in the dihydroxylation of 1-phenylcyclohexene with a complex, formed between OSO4 and the diisobutylbioxazoline (4) (R=CH2CHMe2>, as a stoichiometric reagent (70% ee). Styrene and trans -stilbene afford enantioselec-tivities below 20% ee under these conditions (for highly enantios-elective dihydroxylation catalysts, see Dihydmquinine Acetate and Osmium Tetroxide). 

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]. 

Figure 8.4. Representative ligands used in stoichiometric, asymmetric dihydroxylation reactions, (a) Dihydroquinidine (DHQD) and (b) dihydroquinine (DHQ) are used for stoichiometric osmylation reactions when R = H effective dihydroxylation catalysts result from appropriate modifications at this position (e.g., see Figure 8.5 below). Also, (c) [69] and (d) [70] are examples of C2 symmetrical ligands used in stoichiometric reactions.

P. A. Jacobs, A. Severeyns, D. E. De Vos, L. Fiermans, F. Verpoort, P. J. Grobet. A heterogeneous cis-dihydroxylation catalyst with stable, site-isolated osmium-diolate reaction centres. Angew. Chem. (Int. Ed.), 2001,40 (3), 586-589. 

From their extensive mechanistic studies on the asymmetric dihydroxylation reaction, the Corey group extended the utility of these catalysts to the Strecker reaction.35 Treatment of their dihydroxylation catalyst with trifluoroacetic acid generated a stable crystalline solid 63 that was demonstrated to catalyze the asymmetric Strecker reaction. The TV-allyl moiety was found to be preferred to benzyl as a protecting group for the nitrogen atom. Thus, when 64 was treated with catalyst 63, nitrile product 65 could be obtained in excellent yield. A solvent effect on the % ee was noted such that CH2CI2 was optimal compared to toluene that may compete with the aldimine for the catalyst s binding site. 

Fig. 2.22. Predictive schematic model for enantioselectivity of AD-mix dihydroxylation catalysts. Reproduced from Chem. Rev., 94, 2483 (1994), by permission of the American Chemical Society.

Predict the absolute configuration of the diols obtained from each of the following alkenes using either a dihydroquinidine or a dihydroquinine type dihydroxylation catalysts. 

Site Isolation of the Grubbs Catalyst from the Sharpless Dihydroxylation Catalyst. The Grubbs catalyst was site isolated from AD-mix to complete cascade reactions as shown in eqs 13-15. The Grubbs catalyst was added to the interior of a thimble with CH2Cl2 [BMIM][PF6] and the metathesis reaction was run to completion. Next, the AD-mix was added to the exterior of a thimble with 1 1 (v/v) f-Bu0H H20 or 1 2 3 (v/v/v) [BMIM][PF6] H20 acetone. The product of the metathesis reaction fluxed to the exterior and reacted to yield the diol. 

Coupled redox systems have also been successfully employed in asymmetric catalysis. Krief and coworkers were the first to use air as a terminal oxidant with the Sharpless dihydroxylation catalyst by using benzyl phenyl selenide as a photosensitizer [32-34]. The dihydroxylation of a-methylstyrene using the selenide sensitizer decreases the oxidant waste by over 50-fold compared to the standard oxidation conditions using AD-Mix (KsFelCNJg is the terminal oxidant in AD-Mix) with similar enantiomeric excess and yield [34]. This example of a coupled reaction showcases the potential waste reduction provided by this approach. 

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