Tomiki Hashiyama

Reaction of 3-phenylglycidic esters. Part 1. Stereoselective opening of the oxirane ring of trans-3-phenylglycidic esters with 2-nitrothiophenols and the effect of various catalysts thereon

In the reaction of 2-nitrothiophenol (2) with trans-3-phenylglycidic esters carrying various substituents on the benzene ring, both reactivity and stereoselectivity of the oxirane ring-opening of the glycidates were markedly influenced by the electronic nature of the substituents. The presence of electron-donating groups was favourable for both reactivity and the preferential formation of cis-opening products, while the reverse was true for electron-withdrawing groups. As a result of our investigation on the catalytic effect of various Lewis acids in the reaction of the 4-methoxy derivative (1) with (2), tin compounds were found to be effective catalysts for cis-opening and readily produced the threo-nitro ester (3a), a key intermediate for the synthesis of diltiazem (5).Isolation of the crystalline complex (adduct A) from the reaction of (2) with SnCl4 and its efficient catalytic activity similar to that of SnCl4 suggest that the transition state involves co-ordination of tin derivatives both with (2) and the epoxy oxygen of (1) to cause highly specific cis-opening.

Reaction of 3-phenylglycidic esters. Part 2. Stereo- and regio-selectivity in the oxirane ring opening of methyl trans-3-(4-methoxyphenyl)glycidate with various thiophenols and the effects of solvent and temperature

The effects of the solvent and temperature on the reaction of the trans-glycidate (1) with various substituted thiophenols (2) in the presence or absence of a catalyst have been investigated. The temperature had a surprisingly large effect on the stereochemistry of the oxirane ring-opening of (1). At room temperature, the erythro-isomer (4)(trans-opening product) was obtained as a major product in the absence of catalyst, while the cis-opening product (3)(threo-isomer) was produced predominantly at higher temperature. On the other hand, in a dipolar aprotic solvent, the regioisomer (5) was formed, the yield increasing with the electron-donating ability of the substituents on (2). The formation of compound (5) may involve single-electron transfer as a key step.