Dihydroxy lation

The complex Pd-(-)-sparteine was also used as catalyst in an important reaction. Two groups have simultaneously and independently reported a closely related aerobic oxidative kinetic resolution of secondary alcohols. The oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxy-lation, and aziridination, there are relatively few catalytic enantioselective examples of alcohol oxidation. The two research teams were interested in the metal-catalyzed aerobic oxidation of alcohols to aldehydes and ketones and became involved in extending the scopes of these oxidations to asymmetric catalysis. 

Compare this step to the mechanisms we saw in the previous section syn dihydroxy-lation), and you should see striking similarities. The initial product (shown above) is called a molozonide, and it subsequently undergoes further rearrangements, before ultimately giving the product upon treatment with dimethyl sulfide (DMS). The structure of DMS is ... 

Shi and coworkers developed a method using silyl enol ethers and in situ generated chiral dioxirane derivatives. Lopp and coworkers could develop an asymmetric dihydroxy lation method for racemic 2-hydroxymethyl ketones 202a-c, using TBHP as oxygen source in combination with the Sharpless catalytic system Ti(OPr-i)4/DET, yielding... 

Inferring from kinetic studies, Sharpless had excluded a dihydroxy lation pathway via ap-oxo-bridged bis-osmium intermediate before Kolb, H, C. Andersson, P. G. Bennani, Y. L. Crispino, G. A. Jeong,... 

K. B. Sharpless, Toward an understanding of the high enantioselectivity in the osmium-catalyzed asymmetric dihydroxy-lation (AD). 1. Kinetics,/. Am. Chem. Soc. 1994, 116, 1278-1291. 

Fig. 17.19. cis-wc-Dihydroxy-lation of alkenes with catalytic amounts of Os(VIII)/stoichio-metric amounts of methylmor-pholin-/V-oxide [NMO] top) and with stoichiometric amounts of Os(VIII) (bottom), respectively, and pertinent mechanistic insights obtained thus far. 

Asymmetric dihydroxy lation of substituted aryl allyl ethers also proceeds with high enantioselectivities (89-95% ee) providing that there are no ortho substituents on the aryl group. Dienes, polyenes, and enynes can also be regioselectively dihydrox-ylated (eq 2-5). In some cases, such as in the asymmetric dihy-droxylation of a,3- and 3,y-unsaturated amides, the amount of... 

For additional examples of regioselective asymmetric dihydroxy lations, see Dihydroquinidine Acetate. 

Oxidation of Glycidol. Glycidol is oxidized to glycidic acid with Ruthenium(VIII) Oxide Glycidaldehyde is a mutagenic compound that has been prepared in racemic form by epoxida-tion of Ac role in and in nonracemic forms by the degradation of mannitol. Alternately, (R)- and (5)-glycidaldehyde may be prepared and handled more conveniently via asymmetric dihydroxy lation of acrolein benzene-1,2-dimethanol acetal followed by conversion of the diol to an epoxide (see eq 28). ... 

The protected diol side-chain of 170 is introduced by asymmetric dihydroxy-lation and directs diastereoselectivity in the formation of 172 by hthiation. The most acidic position of 170, between the two methoxy groups, is first protected by silylation. Suzuki couphng of 173 with the boronic acid 174 gives the kinetic product 175 - the more severe hindrance to bond rotation in this compound... 

Analogous substrate t-butyl ( )-hexa-2,4-dienoate was shown to undergo a highly diastereoselective conjugate addition with chiral lithium amides (e.g., N-benzyl-a-methylbenzylamide). Subsequent transformations of intermediate unsaturated aminoester, like iodolactonization or dihydroxy-lation, gave the expected daunosamine derivatives, although with very limited effectiveness [86]. 

Macromolecular metal complexes with modified poly(ethylene oxide)s have also been applied as catalysts for asymmetric reactions epoxidation, dihydroxy-lation, hydrogenation, and hydroformylation. 

The origin of the experimentally observed enantioselectivity in the dihydroxy-lation of styrene was investigated and it was fotmd that ji-interactions between the aromatic rings of ligand and reactant are responsible for the observed enantioselectivity. By parametrization of a Macromodel force field for the reaction, Norrby [42] was able to reproduce (eecaic) the experimentally observed enan-tioselectivities (eeexp). Some examples are shown in Table 2. 

Osmium tetroxide is widely used to synthesize 1,2-diols (the products of 1,2-dihydroxy-lation, sometimes also called glycols). Potassium permanganate can also be used, although because it is a stronger oxidizing agent it is prone to cleave the diol through further oxidation (Section 8.17). 

Catalytic asymmetric dihydroxy lation of alkenes with participation of insoluble polymer-bound cinchoiune alkaloids 99SLI181. 

Thornton, J. E., Fritz, A. and Singh, A. K. Development of Jacobsen Asymmetric Epoxidation and Sharpless Asymmetric Dihydroxy lation Methods for the Large-Scale Preparation of a Chiral Dihydrobenzofuran Epoxide. Org Process Res Dev 7,821-827 (2003). 

Chang, D., Herrnga, M.F., Witholt, B. and Li, Z. (2003) Enantioselective trans dihydroxy-lation of nonactivated C-C double bounds of aliphatic heterocycles with Sphingomonas sp. HXN-200. /. Org. Chem., 68, 8599-8606. 

---