Effect of substituents on the stereoselectivity of the acid-catalysed hydrolysis of a series of aryloxirans. A new application of the Hammett equation

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

“…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).…”

“…~, ~ Our prior work 20*b has shown that the reaction of the trans-3-(4-methoxyphenyl)glycidic ester (1) with 2nitrothiophenol (2) mainly gave the threo-nitro ester (3a), the cis-opening product resulting from attack of the thiol group from the side of the oxirane ring, after prolonged heating in CH,CN. Compound (3a) served as a key intermediate for the synthesis of diltiazem (5), a potent coronary vasodilating agent.2d*e.4 However, this procedure suffers from flaws such as low yield, insufficient stereoselectivity, and too long a reaction time, which have been major obstacles in the synthesis of diltiazem. The reaction of (1) and (2) in the presence of a catalytic amount of NaHCO,, on the other hand, readily gave the undesired erythro-isomer (3b), the trans-opening product resulting from SN2-type attack of thiolate anion.2b These reactions are shown in Scheme 1.…”

Acid-catalyzed hydrolysis of cis- and trans-anethole oxides: discrete carbocation intermediates and syn/anti hydration ratios

“…For example, acidcatalyzed hydrolysis of the "trans" 7,8-diol 9,10-epoxide metabolite of benzo [a] pyrene yields mostly (95%) tetrol from anti hydration, whereas acid-catalyzed hydrolysis of the diastereomeric "cis" 7,8-diol 9,10-epoxide metabolite yields mostly tetrol resulting from syn hydration (85%).8 For hydrolysis of bay-region cis diol epoxides and tetrahydro epoxides in the naphthalene, phenanthrene, chrysene, benz[a]anthracene, and benzo[o]pyrene ring systems, the amount of syn hydration increases with the ability of the aryl group to stabilize positive charge at the benzyl carbon.9•10 The syn/anti hydration ratio in the acidcatalyzed hydrolysis of 1 -arylcyclohexene oxides also varies with substitution in the phenyl ring. 11 The amount of syn hydration is only 7.5 % when the para substituent is nitro but increases to 95 % when the para substituent is methoxy. The stereochemistries of acid-catalyzed addition of water and methanol to 1-phenylcyclohexene oxides and several hexahydrophenanthrene oxides in the gas phase are Several mechanisms have been proposed to explain changes in syn/anti hydration ratios in the acid-catalyzed hydrolysis of aryl-substituted epoxide systems in solution.…”

“…Ail increase in the relative yield of cis diol from hydrolysis of 1-phenylcyclohexene oxides in dilute sulfuric acid solutions was attributed to stabilization of a selectively solvated carbocation 2, leading to cis diol 3, by electrondonating froups in the phenyl ring (Scheme I). 11 It was proposed that a competing reaction via a "borderline A-l" transition-state structure 4 yields trans diol 5.…”

Marked normal salt effects on the stereoselectivity of the ring opening of an aryloxirane in acid media

“…12 The cis adducts (6,8), on the other hand, can be formed by the collapse of a solvent-separated ion-dipole pair 4. This collapse should take place with retention of configuration.12 •13 In such a mechanistic scheme, any factor which increases the stability of the benzylic carbocationic center should sig-nificantly favor intermediate 4, and thus increase the syn/anti ratio. [4][5][6][7] The addition of inert salts produces a rate acceleration and this result has been quantitatively explained on the basis of an increase in polarity of the medium;9•14 the addition of a salt should stabilize ionic transition states more than the reactants, and therefore result in an increase of the rate constant.9•14 Several semiquantitative interpretations of such salt effects have been given,9•15 but most of the theoretical treatments predict a linear relationship between log k and the concentration of the uni-univalent added salt.9 This relation has been, however, inadequately tested9•16 and the dependence of the rate constant on the salt concentration [S] can be better described by the empirical relationship:9•16 fe-fc°(l + 6[S])…”