Vicinal dihydroxylation

Ruthenium complexes alcohol oxidation, 788-9 alkene/alkyne vicinal dihydroxylation, 556 dioxetane decomposition, 1189-90... 

Fig. 4.31 Mechanism of osmium-catalyzed vicinal dihydroxylation of olefins.

A few derivatives of taxol and of deacetylbaccatin III have been synthesized in which the dilferent hydroxyl groups have been modified for structure-activity studies these are described later in Section VII, which deals with pharmacology. However, three reactions bear special mention (a) the intramolecular cyclization of the side chain of taxol leading to the oxazolone (24) (43), (b) an approach to the functionalization of the side chain via vicinal dihydroxylation (11,46) of the cinnamate (25) to give 26, and (c) Sharpless oxyamination leading to mixtures of 2 - and 3 -oxyaminated products (see below). 

The sole other arenediol we know of, phenanthrene-9,10-diol, has an enthalpy of formation derived from the ancient calorimetric resnlts in Reference 88. Acknowledging that there has been some dispute about the enthalpy of formation of the parent hydrocarbon, we adopt the value of 113.0 2.1 kJ moU for phenanthrene . The estimated enthalpy of formation of the phenanthrenediol, based on twice the OH/H increment exchange energy, is —293.8 kJ moU, ca 50 kJ moU more negative than the actual measurement. The apparent destabilization of the real diol is considerably greater than that for the related vicinally dihydroxylated naphthalenes or for catechol. 

This situation obtains for example in the asymmetric vicinal dihydroxylation of olefins (see Fig. 13) reported by Sharpless and coworkers [41]. Coordination of a (chiral) amine to the 0s04 catalyst affords a (chiral) catalyst with much higher activity. 

The vicinal dihydroxylation of double bonds, with Re O, [43], or MeReO, [44], has been further investigated. Based on the different addition mechanism of OsO ... 

However, as mentioned previously, terminal glucose moieties do correlate with the high toxicity of QS-17 and QS-18. Periodate oxidation of QS-18, which presumably destroys the cis vicinal dihydroxyl groups of apiose or galactose, eliminates adjuvant activity. Thus, one or both of these sugars... 

The epoxidation of olefins and the related vicinal dihydroxylation are reactions of great industrial importance. The use of commercially available 30% aq. H2O2 is obviously... 

The osmium-catalyzed vicinal dihydroxylation of olefins with single oxygen donors, typically tert-butyl hydroperoxide or N -methylmorpholine-JV-oxide (NMO), has been known for three decades and forms the basis of the Sharpless asymmetric dihydroxylation of olefins. Recently, Sharpless and coworkers reported that particularly electron-deficient olefins are dihydroxylated more efficiently with NMO (Eq. 2) when the pH of... 

Moving forward from 59, six steps were required to convert this compound to 60. Vicinal dihydroxylation of the olefin was followed by oxidative cleavage of the intermediate diol using lead tetraacetate. Reductive amina-tion of the resulting aldehyde with methylamine, followed by acylation of the intermediate secondary amine gave the desired carbamate. Swern oxidation of the secondary alcohol, followed by enol ether formation gave 60. Elimination of -toluenesulfinic acid from 60 provided 61. Oxidation of this dienol ether to dienone 62 was followed by release of the secondary amine, followed by a conjugate addition reaction to establish the critical C-N bond. The remainder of the synthesis followed known chemistry. The mixture of enones 63 was converted to codeinone (35), codeine (3) and then morphine (1). 

The next task was to convert 42 to ketone 44. This transformation called for a regioselective hydration of the C13-C14 olefin. This was accomplished by vicinal dihydroxylation of the olelin, which was accompanied by formation of the y-lactone (rather that the d lactone). The preference for y-lactonization (which is most often the case in such simations) left the C14 hydroxyl group free for oxidation to ketone 43. Reductive cleavage of the a-C-O bond, and esterification of the resulting acid, gave 44 (see 99 to 100 in Alkaloids-12 for comparison). 

Treatment of 47 with alumina gave a separable 1 1 mixture of intramolecular aldol condensation products 48 and 49. The required isomer (48) was converted to the mesylate and dehydration afforded 50. Reduction of 50 from the convex face of the dithiaoctalone gave 51 after protection of the alcohol with a MOM group. Vicinal dihydroxylation of the olefin from the most accessible face, and acetonide formation, completed the synthesis of 38 (R=MOM). 

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