Trans 1,2-diols

Sulfurane reagent lor conversion of trans diols to epoxides, generally for dehydration of diols to olefins or cyclic ethers, and as an oxidizing agent... 

The trans-diol remains in the mother liquor and may be recovered by complete evaporation of the solvent followed by recrystallization of the residue from pentane. The yield of trans-1,2-cyclodecanediol is 38-45 g. (27-32%), m.p. 53-54°. 

Tetramethoxybutane, TMOF, MeOH, CSA, 54-91% yield, trans-Diols are protected in preference to c/5-diols, in contrast to acetonide formation, which prefers protection of cis-diols." ... 

Diols can be prepared either by direct hydroxylation of an alkene with 0s04 followed by reduction with NaHSOj or by acid-catalyzed hydrolysis of an epoxide (Section 7.8). The 0s04 reaction occurs with syn stereochemistry to give a cis diol, and epoxide opening occurs with anti stereochemistry to give a trans diol. 

An alternative method for generating enriched 1,2-diols from meso-epoxides consists of asymmetric copolymerization with carbon dioxide. Nozaki demonstrated that a zinc complex formed in situ from diethylzinc and diphenylprolinol catalyzed the copolymerization with cyclohexene oxide in high yield. Alkaline hydrolysis of the isotactic polymer then liberated the trans diol in 94% yield and 70% ee (Scheme 7.20) [40]. Coates later found that other zinc complexes such as 12 are also effective in forming isotactic polymers [41-42]. 

When 3-thiolene dioxide is treated with hydrogen peroxide, the corresponding epoxide is obtained313. The 3,4-trans-diols can be obtained by hydrolysis under acidic conditions (equation 120). 

Diboran greift als starke Lewis-Saure C,C-Mehrfachbindungen etwa gleich schnell wie die Carboxy-Gruppe an1, wobei die C=C-Doppelbindungen ris-hydroboriert werden. Nach Oxidation mit alkalischem Wasserstoffperoxid werden die entsprechenden trans-Diole erhalten (weiteres s. S. 50ff.)2. 

Within the diastereomeric switch sequences, the corresponding trans-diols become accessible either using a Mitsunobu inversion or a reversible Diels-Alder cyclization as key reaction step [249,250]. This synthetic strategy is complementary to an approach involving metabolic engineering of E. coli via the chorismate/ isochorismate pathway [251]. 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

In mammals, dieldrin and endrin are also converted into keto metabolites (Figure 5.5). In the rat, the keto metabolite is only a minor product, which, because of its lipophilicity, tends to be stored in fat. With endrin, a keto metabolite is formed by the dehydrogenation of the primary monohydroxy metabolite. In mammals, the trans diol of dieldrin is converted into a diacid in vivo (Oda and Muller 1972). 

A solution of lead tetraacetate in pyridine rapidly oxidises the most recalcitrant trans-diols, especially if a considerable excess of oxidant (3-4 moles) is used, implying yet a further mechanism for the action of this versatile oxidant ... 

Acid-catalyzed hydrolysis of 1,2-epoxy cyclopentane yields a trans-diol, trans-, 2-cyclopentanediol. 

Tetrahydroepoxides as models. Since the quantum chemical calculations apply most rigorously to the simple benzo-ring tetrahydroepoxides and since the calculations neglect influences of the hydroxyl groups in the diol epoxides, it is instructive first to examine the benzo-ring tetrahydroepoxides as simplified models for the reactive site in the diol epoxides. Most of the information about tetrahydroepoxide reactivity derives from studies of the kinetics of their hydrolysis reactions, in which cis- and trans-diols, as well as tetrahydroketones can be formed (Equation 5). 

Our understanding of the importance of steric factors was initiated by structure determinations by X-ray diffraction techniques of two trans-diols of benz[a]anthracene (89), XVI and XVII, shown in Figure 12. The crystal structures showed diequatorial... 

Figure 12. The structures of two trans diols of benz[a]anthracene showing the diequatorial conformation of the unhindered 10,11-diol and the diaxial conformation of the hindered 1,2-diol. These trends persist in solution where the 10,11-diol exists as an equilibrium of 30% axial and 70% equatorial conformers (that is, the ring is flexible) on the other hand the 1,2-diol is 100% diaxial even in solution. If the 1-hydroxyl group were equatorial it would "bump" into the hydrogen atom on Cl2.

Figure 19. Perpendicularity of the PAH and the base. Conformations of trans-diols. The steric hindrance in a bay region will cause hydroxyl or other substituents (such as DNA) to lie in an axial orientation. Sites where this occurs are marked "a". Those sites where there is no steric hindrance are marked "ae" (axial or equatorial). The conclusion is that when a diol epoxide alkylates DNA the base on DNA will be bonded axially to the PAH group.

Fig. 10.11. Chemical mechanisms in the hydrolysis ofK-region epoxides. Pathway a characteristic proton-catalyzed hydrolysis under acidic conditions Pathway b nucleophilic hydrolysis by H2C) Pathway c HO"-catalyzed hydrolysis under basic conditions. Pathways b and c form the trans-diol. In the case of Pathway a, partial configurational inversion may occur at the carbonium ion, resulting in a mixture of the trans- and cw-diols. 

Intramolecular coupling Some aromatic diketones have been stereoselectively cy-clized under various electrolysis conditions, which, together with the substrate structure, strongly influence the stereochemistry of the formed cyclic diol. Reductive cyclization of 1,8-diaroylnaphthalenes led to trans-diols, 2,2 -diaroylbiphenyls and a, )-diaroylalkanes yielded cis-diols with different stereoselectivities depending on substrate structure and electrolysis conditions (pH, cosolvent) (Fig. 57) [310-312]. 

The rate of dehydration of the cis diol was about fifty times slower than that of the trans diol and the product of the reaction consisted mainly of cyclohexenol. The 1,4-epoxycyclohexane formed in the reaction was formed after a prior epimerization of the cis to the trans diol this was demonstrated by means of tritium tracer technique. When irons-1,4-cyclohexanediol was dissolved in ieri-butyl alcohol-T having the hydroxyl hydrogen marked with tritium (C4H,OT) the 1,4-epoxycyclohexane produced in this reaction had a very low tritium content. A similar reaction carried out with cis-1,4-cyclohexanediol produced a highly tritiated 1,4-epoxycyclohexane. The insertion of tritium in the 1,4-epoxycyclohexane produced from the cis diol can be explained as follows ... 

In connection with our own work on the enzyme-catalysed hydrolysis of cyclohexene epoxide with various fungi we made the unexpected observation that the microorganism Corynesporia casssiicola DSM 62475 was able to interconvert the (1R,2R) and (1S,2S) enantiomers of the product, trans cyclohexan-1,2-dioI 25. As the reaction proceeded the (1R,2R) enantiomer was converted to the (1S,2S) enantiomer [20]. If the racemic trans diol 25 was incubated with the growing fungus over 5 days, optically pure (> 99 % e. e.) (1 S,2S) diol 25 could be isolated in 85% yield. Similarly biotransformation of cis (meso) cycIohexan-1,2-diol 26 yielded the (1S,2S) diol 25 in 41 % (unoptimized) yield (Scheme 11). 

Incubation of the (1R,2R) diol 25 over a shorter time period of 4 days gave a mixture of the meso cis diol 26 (26%) and the trans diol 25 RR/SS 76 26) showing conversion over to the (1S,2S) diol. As with the previous examples, no conversion was observed when using the S,S diol 25 as a substrate. Although no intermediate a-hydroxyketone was observed for this substrate we proposed the operation of at least two dehydrogenase enzymes, DH-1 and DH-2, catalysing the (i )-selective oxidation and (S)-selective reduction respectively (Scheme 12). Incubation of cis cycloheptan-l,2-diol afforded only the (S)-2-... 

Closely related substrates such as )5-methyl styrene epoxide and dihydro-naphthalene epoxide and derived trans diols were not substrates for this particular microorganism. 

Obviously with the indan-l,2-diol substrates there is no symmetrical meso intermediate which makes interpretation of the mechanism more difficult. In both the cyclohexan-l,2-diol and the indan-l,2-diol series the trans diols react faster and cis diols (both enantiomers for indandiol) are seen as intermediates. The (IS,2R) cis indandiol 29 is faster reacting and on incubation of the racemate only a very small trace of the R,R)-trans 28 isomer is observed. 2-Hydroxyin-dan-1 -one 30, an observed intermediate in these biotransformations, undergoes kinetic resolution when incubated as a racemic substrate. The faster reacting enantiomer is reduced to the faster reacting cis (lS,2i )-indan-l,2-diol 29 which is subsequently transformed into both trans diols and ultimately the (S,S)-iso-mer. Current work is focussing on determining the absolute configuration of the intermediate a-hydroxyketone 30. 

However, oxidation with H2O2 in acetone resulted in a high diol selectivity with an equilibrium mixture of the cis- and trans-diols, illustrating the role of the residual acidity of the support The reaction is suggested to occur via heterolyhc cleavage of the vanadium peroxo species. Less than 0.5% leaching of the bipy complex was observed over 50 h of operation. 

The formation of the pyrrolidone group involves condensation of an acetate with L-serine. Since a significant proportion of L-[l,2,3-l3C, 15N]serine was incorporated into pramanicin, the carbon skeleton of serine is incorporated intact. Acylation with the 14-carbon moiety then ensues leading to the conjugated dieneone tetramic acid intermediate 122. In fact, this compound co-occurs with 121 and, interestingly, is almost exclusively produced when 123 and 124 are used as precursors. The remaining steps involve formation of the trans-diol at C-3 and C-4 and ep-oxidation of the terminal alkene in the dienone chain. 

Scheme 3.4 Bioactivation of benzo[o]pyrene to the ultimate carcinogen , 7,8-trans-diol-9,10-epoxide. Modified from [42].

---