Olefin enantioselective dihydroxylation

Over the years, the original dihydroxylation procedure has been modified to operate catalytically, more rapidly, and in better yield. However, the last remaining task, making the dihydroxylation of a prochiral olefin enantioselective without losing all the other desirable features of the reaction, has only recently become a reality. 

Mono-, di-, and trisubstituted olefins undergo osmium-catalyzed enantioselective dihydroxylation in the presence of the (R)-proline-substituted hydroquinidine 3.9 to give diols in 67-95% yields and in 78-99% ee.75 Using potassium osmate(VI) as the catalyst and potassium carbonate as the base in a tm-butanol/water mixture as the solvent, olefins are dihydroxylated stereo- and enantioselectively in the presence of 3.9 and potassium ferricyanide with sodium chlorite as the stoichiometric oxidant the yields and enantiomeric excesses of the... 

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... 

TABLE 4-14. Enantioselective Dihydroxylation of Olefins Using 0s04 92b R1 1.0s04,92b, -78 °C HO OH... 

Recently, effective chiral ligands for the enantioselective dihydroxylation of olefins have been intensively investigated. Among the reported asymmetric dihydroxylation systems, the superiority of an H20/f-Bu0H-K3Fe(CN)6/K2C03 system with chiral ligands, that is, dihydroquinidine (DHQD) and/or a dihydroquinine (DHQ) derivative, has been mentioned (see Sect. 15.2.4.7) [476]. 

New catalyst design further highlights the utility of the scaffold and functional moieties of the Cinchona alkaloids. his-Cinchona alkaloid derivative 43 was developed by Corey [49] for enantioselective dihydroxylation of olefins with OsO. The catalyst was later employed in the Strecker hydrocyanation of iV-allyl aldimines. The mechanistic logic behind the catalyst for the Strecker reaction presents a chiral ammonium salt of the catalyst 43 (in the presence of a conjugate acid) that would stabilize the aldimine already activated via hydrogen-bonding to the protonated quinuclidine moiety. Nucleophilic attack by cyanide ion to the imine would give an a-amino nitrile product (Scheme 10). 

Petri, A., Pini, D. and Salvadori, P. Heterogeneous enantioselective dihydroxylation of aliphatic olefins - A comparison between different polymeric cinchona alkaloid derivatives, Tetrahedron Lett., 1995, 36, 1549-1552. 

CAimHPFf ] [CgQimHPFe] and others K2[0s02(0H)4] NMO K3[Fe(CN)6] k2co3 Enantioselective dihydroxylation of olefins with H20 and t-BuOH as co-solvents detailed study on reaction parameters product extracted with Et20 activity and selectivity stable for 9 runs, then considerable decrease osmium contamination in the product < 7 ppb. [64] [65]... 

C.CjimHPFe] 0s04 NMO Enantioselective dihydroxylation of olefins with H20 and t-butanol as co-solvents products extracted with Et20 addition of an amine ligand significantly improves catalyst retention catalyst recycled 5 times, activity decreases only slowly. [62]... 

QCjimJtPFe] CjimlfSbFs] 0s04 NMO Enantioselective dihydroxylation of aryl olefins with acetone-H20 as co-solvent 2.5-5 equivalents of chiral ligand added products extracted with Et20 catalyst reused four times, marked decrease in activity after the third run. [67]... 

Corey, E. J., Noe, M. C., Grogan, M. J. A mechanistically designed mono-cinchona alkaloid is an excellent catalyst for the enantioselective dihydroxylation of olefins. Tetrahedron Lett. 1994, 35, 6427-6430. 

An extended addition increases the effective mole ratio of reaction components, which can have a beneficial impact on reaction selectivity. This is particularly true for reactions using catalysts. In the dihydroxylations in Figure 8.7, olefin 13 was added over 6 hours in order to ensure high enantiomeric purity of the product [6], Excess olefin, which accumulates if the addition rate is faster than the reaction rate, is thought to coordinate with the catalyst in a fashion that leads to non-enantioselective dihydroxylation [6]. In the osmium-mediated dihydroxylation of... 

Osmium tetroxide is very expensive and very toxic which made using it quite unattractive. For a long time, many people who used osmium tetroxide to convert olefins to diols—and this was long before enantioselective dihydroxylations came on the scene—used the Upjohn procedure.20 This process used catalytic amounts of osmium tetroxide, NMO (/V-methylmorpholine /V-oxidc) 87 as the stoichiometric oxidant, and one solvent phase. The solvent was water, acetone and tert-butyl alcohol. The osmate ester 86 was hydrolysed under these conditions and the osmium (VI) species was reoxidised to 0s04 by NMO. 

The discussion about the possible formation of metalla-2-oxetanes in transition metal-mediated oxidation reactions began with the ground breaking work of Sharpless in the field of enantioselective dihydroxylation of olefins with osmium tetraoxide using cinchona alkaloids as ligands [6]. The transfer of the stereochemical information of the chiral ligand to the substrate was explained by Sharpless with a two-step mechanism for the addition reaction, which should occur rather than a concerted [3+2] addition as originally proposed [110] (Fig. 15). 

Fig. 19 Reaction mechanism for the enantioselective dihydroxylation of olefins with OsO in the presence of chiral ligands L via [3+2] addition suggested by Corey...

Tetrasubstituted enol ethers such as (5.44) undergo dihydroxylation using PYR ligands with good ee, but for other tetrasubstituted olefins, enantioselectivities tend to be reduced and isolated yields also suffer. 

A Veldkamp and G. Frenking, /. Am. Chem. Soc., 116, 4937 (1994). Mechanism of the Enantioselective Dihydroxylation of Olefins by OSO4 in the Presence of Chiral Bases. Theoretical Studies of Organometallic Compounds. Vlll. 

Scheme 1.4 Catalytic cycle for the enantioselective dihydroxylation of olefins using (DHQDjjPHAL for oxygen transfer and as a source of chirality...

Scheme 7.80 Enantioselective dihydroxylation of olefins catalyzed by sulfur-containing chiral diselenide 499...

Another useful method for the asymmetric oxidation of enol derivatives is osmium-mediated dihydroxylation using cinchona alkaloid as the chiral auxiliary. The oxidation of enol ethers and enol silyl ethers proceeds with enantioselectivity as high as that of the corresponding dihydroxylation of olefins (vide infra) (Scheme 30).139 It is noteworthy that the oxidation of E- and Z-enol ethers gives the same product, and the E/Z ratio of the substrates does not strongly affect the... 

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