Propargylic triols

Fig. 3 Preferred cyclization modes of 1,3-anti and l,3-xy propargylic triols...

In this type of study, the terminally-CF3 propargylic alcohol (S)- derived from the enzymatic resolution is also a useful intermediate. This material is transformed into the corresponding E- and Z-allylic alcohols after successful enzymatic optical resolution. Os04-catalyzed oxidation eventually led to the formation of the desired triols 30 in a diastereoselective manner. 

Allylic and propargylic 3-keto sulfoxides could be reduced as well as saturated compounds. Optically active allylic 3-hydroxy sulfoxides present some specific interest because of the possible hydroxylation of the double bond leading to vicinal triols. The osmium tetroxide catalyzed hydroxylation reaction of the double bond in the presence of trimethylamine N-oxide is highly stereoselective the (/ ,/ )-3-hydroxy sulfoxide gave only one diastereoisomeric triol as a result of a cis hydroxylation of the double bond and a symbiotic effect of the two chiral centers in the asymmetric induction (the (S,/ )-isomer gave a lower de). 

Naturally occurring (l S, 25, 3i )-4-hydroxymethylcyclopent-4-ene-l,2,3--triol (950) plays a central role in the ability of a non-aristeromycin producing mutant strain of Streptomyces citricolor to support production of both aristeromycin and neplanocin. Swem oxidation of readily available 13 from L-tartaric acid provides the aldehyde 943 which, when treated with an excess of propargyl zinc bromide, leads to a 2.3 1 diastereomeric mixture of acetylenic alcohols 944. Silylation of the hydroxyl group with TBSOTf and subsequent saponification of the ester group yields the carboxylic acid 945 in 74% overall yield from 13. Interestingly, Dess-Martin oxidation of 943 provides the allenic ketone 946, which is unstable to base and cannot be used in the subsequent radical cyclizations. 

The synthesis of 188 from epoxide 189 was done as shown in Scheme 25. Epoxide opening with a propargyl alane reagent [124], protection-deprotection of the alcohol functions, and Redal reduction led to the -allylic alcohol 194, also obtained by another route [116]. Asymmetric epoxidation-Redal epoxide opening [60-62] followed by silylation and debenzylation led to intermediate triol 195. Selective six-membered acetal formation and primary alcohol oxidation then furnished building block 188. 

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