Enantioselective Dihydroxylations of Olefins

The Sharpless catalytic asymmetric dihydroxylation reaction has found countless applications in synthesis, of which only a few illustrative examples are discussed. The enantioselective synthesis of the side chain 318 of the anticancer agent paclitaxel (Taxol, 320) has attracted much interest. Its preparation was accomplished on a mole-scale by Sharpless through the use of 

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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). 

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]... 

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. 

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...

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... 

Corey et al.66 have developed a bidentate chiral ligand 93 for asymmetric dihydroxylation of olefins. As shown in Table 4-13, asymmetric dihydroxylation of a series of olefins using 93 as a chiral catalyst and OsCU as the oxidant gives good to excellent yield as well as good enantioselectivity in most cases. 

Hirama and co-workers71 developed another chiral bidentate ligand 92 for OsCU-mediated dihydroxylation of /m .v-disubstituted and monosubstituted olefins. As shown in Table 4-14, asymmetric dihydroxylation of olefins using (S,S)-(—)-92b as the chiral ligand provides excellent yield and enantioselectivity. 

Along with catalytic asymmetric epoxidation, the related dihydroxylation of olefins is another venerable catalytic enantioselective process that is widely used by the modern organic chemist. An application of this important transformation may be found in Corey s 1994 preparation of optically pure 109 (Scheme 16), an intermediate in Corey s 1985 total synthesis of ovalicin.1181 The catalytic asymmetric dihydroxylation that affords 108 solves one of the most challenging problems in the total synthesis installment of the tertiary alcohol center with the appropriate relative and absolute stereochemistry. 

Enantioselective c -dihydroxylation of olefins using osmium catalyst in the presence of cinchona alkaloid ligands. 

A polymeric cinchona alkaloid-derived ligand 44 was prepared and used to catalyze the asymmetric dihydroxylation of olefins (see the diagram below).66 Both aliphatic and aromatic olefins afforded diols with good enantioselectivities. 

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. 

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. 

Beller et al. [85] recently described the aerobic dihydroxylation of olefins catalyzed by osmium at basic pH, as mentioned above. When using the hydroquini-dine and hydroquinine bases, they were able to obtain reasonable enantioselectivities (54% ee to 96% ee) for a range of substrates. An alternative route towards enantiopure diols, is the kinetic resolution of racemic epoxides via enantioselec-tive hydrolysis catalyzed by a Co(III)salen acetate complex, developed by Jacob-... 

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]... 

The combination of K2[0s02(0H)4] or 0s04 with chiral alkaloid ligands affords highly recyclable systems for the dihydroxylation of olefins. Bis-Chinona alkaloid ligands containing phthalazine or pyrimidine backbones, as shown in Figure 5.8, provide superb enantioselectivity and different models have been devised to rationalise the chirality transfer/71,721... 

Enantioselective oxidation of olefins is a very elegant way of introducing oxygen and in some cases also nitrogen functions into molecules. The catalytic methods with the highest industrial potential are epoxidation and dihydroxylation, and the kinetic resolution of racemic terminal epoxides (Table 3). 

Huang, J., Corey, E. J. A Mechanistically Guided Design Leads to the Synthesis of an Efficient and Practical New Reagent for the Highly Enantioselective, Catalytic Dihydroxylation of Olefins. Org. Lett. 2003, 5, 3455-3458. 

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