Triols synthesis

Bodnar, P. M., Shaw, J. T., Woerpel, K. A. Tandem Aldol-Tishchenko Reactions of Lithium Enolates A Highly Stereoselective Method for Diol and Triol Synthesis. J. Org. them. 1997, 62, 5674-5675. 

Scheme 3-76. Stereoselective triol synthesis through palladium-catalyzed intramolecular disilylation of alkenes followed by the Tamao-Fleming oxidation.

Lligadas, G., Ronda, J.C., Gaha, M., Cadiz, V., 2007. Polyurethane netwa-ks from fatty-add-based aromatic triols synthesis and characterization. Biomacromolecules 8,1858-1864. 

Review Problem 15 This triol (TM 192) can be taken as a 1,4- or a 1,5-dioxygenated compound. In fact only one of these will work. Suggest a synthesis. 

Another synthesis of pyrogaHol is hydrolysis of cyclohexane-l,2,3-trione-l,3-dioxime derived from cyclohexanone and sodium nitrite (16). The dehydrogenation of cyclohexane-1,2,3-triol over platinum-group metal catalysts has been reported (17) (see Platinum-GROUP metals). Other catalysts, such as nickel, rhenium, and silver, have also been claimed for this reaction (18). 

Cyclohexane-la,3a,5a-triol (i j -hexahydrophloroglucinol, a-phloroglucite) is a starting material in Woodward s synthesis of prostaglandin 2oc and... 

Many of the reactions already discussed for the preparation of bis-oxygenated pregnanes can also be used for the synthesis of 17,20,21-tris-oxygenated pregnanes by proper choice of substrate. Thus, reaction of a 17-vinyl-17-hydroxy steroid or a A -21-hydroxypregnene with osmium tetroxide will give the 17,20,21-triol, and the Stork reaction can be applied to 17a-hydroxy-20-keto steroids. 

A variant of the Williamson ether synthesis uses thallium alkoxides. The higher reactivity of these can be of advantage in the synthesis of ethers from diols, triols and hydroxy carboxylic acids, as well as from secondary and tertiary alcohols on the other hand however thallium compounds are highly toxic. 

The general features of the monensin synthesis conducted by Kishi et al. are outlined, in retrosynthetic format, in Scheme 1. It was decided to delay the construction of monensin s spiroketal substructure, the l,6-dioxaspiro[4.5]decane framework, to a very late stage in the synthesis (see Scheme 1). It seemed reasonable to expect that exposure of the keto triol resulting from the hydrogen-olysis of the C-5 benzyl ether in 2 to an acidic medium could, under equilibrating conditions, result in the formation of the spiroketal in 1. This proposition was based on the reasonable assumption that the configuration of the spiroketal carbon (C-9) in monensin corresponds to the thermodynamically most stable form, as is the case for most spiroketal-containing natural products.19 Spiro-ketals found in nature usually adopt conformations in which steric effects are minimized and anomeric effects are maximized. 

From intermediate 43, the path to monensin would seemingly be straightforward. A significant task which would remain would be the construction of the l,6-dioxaspiro[4.5]decane substructure of monensin. You will note that the oxygen atoms affixed to carbons 5 and 12 in 43 reside in proximity to the ketone carbonyl at C-9. In such a favorable setting, it is conceivable that the action of acid on 43 could induce cleavage of both triethylsilyl ethers to give a keto triol which could then participate in a spontaneous, thermodynamically controlled spiroketalization reaction. Saponification of the C-l methyl ester would then complete the synthesis of monensin. 

Scheme 14 Efficient formation of the seven-membered A ring from unprotected triol 75 in Holton s total synthesis of hemibrevetoxin B (77) [61]...

Because the condensation between a diketene acetal and a diol proceeds without the evolution of volatile byproducts, this method allows the preparation of dense, crossUnked materials by using reagents having a functionality greater than 2 (15). Even though either or both the ketene acetal and alcohol could have functionalities greater than 2, only triols were investigated because the synthesis of trifunctional ketene acetals is extremely difficult. 

Since the chemical addition of HCN always results in mixtures of cis/trans-isomers, the stereoselective HNL-catalyzed addition is of great advantage in the synthesis of natural products. The syntheses of the natural monoterpenes cis-p-menth-8-ene-l,7-diol and cA-/ -menthane-l,7,8-triol are interesting examples for the application of this methodology (Scheme 9). ... 

Scheme 9 Stereoselective synthesis of cw-p-menthane-l,7,8-triol (A) and cA-p-menth-8-ene-l,7-diol (B).

Me, m-OMe, m-Cl, m-CF3, etc.) have been prepared by hydrolysis of the corresponding X-C6H4Si(OMe)3 compounds in an H20/MeOH mixture. Again, the formation of an alcohol, MeOH, rather than a hydrogen halide is beneficial in the synthesis of such sensitive triols (102). 

RhH(PPh3)4 (1 mol%) exhibited higher catalytic activity and promoted a complete reversal in stereoselectivity to provide the trans isomer of 24 and 25 as the major reaction product. The czs-cyclopentane 29, derived from optically active 28, was converted to the differentially protected cyclopentane triol 29, which, in turn, converted to the differentially protected tetrad 30, a key intermediate in the synthesis of enantiopure bioactive carbo-cyclic nucleosides [19]. 

A Garzon, A Poupaert, M Claesen, P Dumont. A lymphotropic prodrug of L-dopa Synthesis, pharmacological properties, and pharmacokinetic behavior of 1,3-dihex-adecanoyl-2-r(S)-2-amino-3-(3,4-dihydroxyphenyl) propanoyl] propane-1,2,3-triol. J Med Chem 29 687-691, 1986. 

In Morimoto s total synthesis of (-t-)-eurylene and (+)-14-deacetyleurylene, the pivotal steps are the construction of trans- and cw-tetrahydrofuran rings via a hydroxy-directed syn oxidative cyclization of acyclic bishomoallylic alcohols promoted by Re(VII) and Cr(VI) oxides, respectively. As depicted below, the trans-THF is achieved by treatment of the triol with the oxorhenium(VII) complex, and the cis-THF is constructed by the use of PCC <00AG(E)4082>. 

Synthetic transformations of the products of the intramolecular bis-silylation have been examined. The five-membered ring products derived from homopropargylic alcohols were hydrogenated in a stereoselective manner (Scheme ll).90 Oxidation of the products under the Tamao oxidation conditions (H202/F /base)96 leads to the stereoselective synthesis of 1,2,4-triols. This method can be complementary to the one involving intramolecular bis-silylation of homoallylic alcohols (vide infra). 

Pentitol synthesis An asymmetric synthesis of L-arabinitol involves condensation of the (E)-a,fJ-unsaturated ester (2) with the anion of methyl (R)-p-tolyl sulfoxide (1). The resulting p-keto sulfoxide (3) is reduced stereoselectively by ZnCl2/DIBAH (13, 115-116) to 4. Osmylation of 4 with (CH,)3NO and a catalytic amount of 0s04 (13, 224-225) yields essentially a single triol (5). Finally, a Pum-merer rearrangement of the sulfoxide followed by reduction of an intermediate... 

The conventional thinking in organic synthesis indicates that primary hydroxyls are more reactive than secondary hydroxyls [96], Under this assumption, the glycosylation of triol 157 to furnish diol 158 by exclusive glycosylation at the... 

Fujino, A., Asano, M., Yamaguchi, H., Shirasaka, N., Sakoda, A., Ikunaka, M., Obata, R., Nishiyama, S. and Sugai, T., Bacillus subtilis epoxide hydrolase-catalyzed preparation of enan-tiopure 2-methylpropane-l,2,3-triol monobenzyl ether and its application to expeditious synthesis of (R)-hicalutamide. Tetrahedron Lett., 2007, 48, 979. 

Assuming that the synthesis, i.e. the reaction of the tetra-acid chloride with racemic t/zreo-aminotriol will result into a statistical distribution, the probability of formation of all isomers should be identical. These isomers are illustrated schematically in Fig. 20 where the configuration (2R,3S) of the 3-amino-butane-1,2,4-triol is abbreviated as a and 2S,3R) as b . 

---