Diol hydroxyacetals

Related hydride shifts have been proposed to account for stereoselective gas-phase reactions of epimeric alkoxides of cyclic diols (Beloeil et al., 1983) and of bicyclic hydroxyacetals (Tabet et al., 1985). 

At temperatures around 200°, a-hydroxyacetates are transformed to oxiranes via a tautomeric ortho-monoester with neighboring-group participation. By the action of heat. CO2 is split off the carbonic acid esters of 1,2-diols and oxiranes are formed. Disecondary or ditertiary 1,2-diols react with diaryldialkoxysulfurane 66 by antiperiplanar intramolecular nucloephilic displacement via a (3-hydroxy-alkoxysulfonium ion intermediate 67 (Eq. 56). ... 

When the mixture of high boiling products was acetylated, VIII and IX were smoothly converted to the diacetate, X. This proved that both the hydroxyacetates and the diacetate had the same oxygen attachment positions. However, these results do not preclude a 1,3-diol type structure. 

The double Henry reaction was examined by Luzzio and Fitch for the synthesis of a key intermediate 21 of perhydrohistrionicotoxin (22) [3]. Reaction of nitroalkane 15 and glutaraldehyde 16 using TMG (3) in dry tetrahydrofiiran (THF) proceeded via a double nitroaldol reaction to give meso-17 in 80-87% yield. After conversion of the diol to meso lactamdiacetate 19, esterase mediated hydrolysis gave optically active 20 in 87% yield with 93% ee (Scheme 7.2). This hydroxyacetate was successfully led to the Kishi lactam (21) [4], a key intermediate for 22. 

The synthesis of the monoacetal 24 (Scheme 10) starts from the key vitamin A intermediate 73. Acetalization with 2,2-dimethylpropane-l,3-diol furnished the acetoxyacetal 95 in high yield. Transesterification of 95 with methanol in the presence of a catalytic amount of sodium methoxide, followed by work-up and distillation, provided the hydroxyacetal 96 in nearly quantitative yield. 

In a synthesis of tropane alkaloids 65, the strategy started with diastereoselective 1,4-diacetoxylation of diene 59 (Scheme 11.20) [83]. The diacetate 60 obtained was converted to diol 61 and subjected to an enzymatic transesterification to give hydroxyacetate 62 with 98% ee. Hydroxyacetate 62 was transformed into acetal 63 by a selenium-based [2,3]-sigmatropic rearrangement. The acetal 63 was transformed into the target tropane alkaloid 65 via ketone 64. By changing the reactivity of the allylic oxygen functions in the enantiomerically pure monoacetate 62, the enantiomer of 65 was also obtained. 

The combination of A -bromoacetamidc, silver acetate, and dry acetic acid has been shown to be superior to Woodward s procedure for the rfy-hydroxylation of olefins. Work up of the reaction mixture is simply effected by hydrolysis of the dioxolenium ion, followed by cleavage of the hydroxyacetate intermediate with lithium aluminium hydride. The use of a co-oxidant, such as sodium chlorate or hydrogen peroxide, allows the addition of catalytic quantities of osmium tetroxide to prepare c/y-diols from olefins. However the reaction is often complicated by further oxidation of the glycol to the a-ketol. The use of tertiary amine A -oxides, particularly A -methylmorpholine A -oxide, prevents this oxidation and gives higher yields of the desired product (Table 6). Another variation on this theme employs... 

Alkoxyacoxy compounds from ) -ketoacetals via ) -hydroxyacetals and 1,3-diol monoethers... 

---