Hydrogen participation vs. elimination. The role and fate of neighboring hydrogen in solvolysis of neomenthyl tosylate

Abstract

Product composition and a d 1 and P-d3 isotope effects in the solvolysis of neomenthyl tosylate (8-OTs) were determined in 70% aqueous trifluoroethanol and 70% aqueous ethanol. Both trifluoroethanolysis and ethanolysis gave I-2% neomenthol(97% d3), 12-13% cis-4-menthanol(l00% d3), 2-3% trans-4-menthanol(lOO% d3), 66-70% 3-p-menthene (83% d3 and 17% dz), and 5-9% 4,8-p-menthene (97% d3), respectively. These results and the high value of the P-d3 isotope effect ( k H / k D = 2.45) were interpreted in terms of rate-determining hydride shift followed by elimination which accounts for 75% of all products. In 85% of the elimination products the migrating hydrogen (deuterium) is not the one being eliminated.Axial cyclohexyl derivatives such as neomenthyl tosylate (8-OTs) yield, under solvolytic conditions, predominantly elimination products.' The antiperiplanar arrangement of the leaving group and the axial tertiary P-hydrogen atom provide the ideal geometry for hyperconjugation and hydrogen participationa2 It has been shown that both of these interactions can be conveniently studied by means of secondary deuterium isotope e f f e~t s .~ Previous studies of the solvolysis of unlabeled derivatives4+ could not provide satisfactory answers to questions regarding the participation of neighboring hydrogen in the rate-determining step (possibly via a bridged intermediate) and the fate of this hydrogen in the (subsequent) elimination reaction. Therefore, we considered it of interest to perform a detailed kinetic and product study of the solvolysis of neomenthyl tosylate (8-OTs) and its specifically deuterated analogues 6-OTs and 3-OTs. The synthesis of this material as well as of 3-p-menthene (10) and 2-p-menthene (ll), respectively, and the isomeric cis-and tram-6menthanols (12 and 131, which were needed for the purpose of identification and product characterization, is given in Schemes

Secondary α-Deuterium Kinetic Isotope Effects: Assumptions Simplifying Interpretations of Mechanisms of Solvolyses of Secondary Alkyl Sulfonates

“…McLennan questioned the proposed 1,11 maximum α-KIE of 1.22−1.23, calculated on the basis of Me as an alkyl group (rather than a secondary alkyl group), and suggested a maximum α-KIE of 1.35 . This proposal is supported by the recent example of an α-KIE of 1.33 for solvolysis of 3 4f. In addition, solvolyses of p -methoxybenzal chloride show α-KIEs up to 1.21,which is significantly higher than the “maximum” of 1.15 expected for chloride as a leaving group. , …”

“…While each mechanism and quantitative fit has been carefully argued, , and by itself appears reasonable, 11 different rate-determining steps (RDS) have now been proposed for solvolyses of various secondary alkyl substrates ( k 1 , k 2 , k 4 , k 5e , and k 5s (Scheme ), 2 for H-migration, 2 for alkyl migration, and 2 others; details are given in the Supporting Information, Table S1). ,,, The present study was prompted by a recent report proposing a new mechanism for solvolyses of the stannyl adamantyl brosylate ( 2 ),4f based in part on an unexpectedly high α-deuterium kinetic isotope effect (α-KIE) of 1.33. Assumptions underlying the interpretations of α-KIEs are reexamined and alternatives leading to fewer RDS are proposed.…”

“…Three assumptions proposed previously about α-KIEs for single steps are as follows: (1) only α-KIEs < 1.08 are consistent with S N 2 reactions ( k 4 ), so alternative mechanisms are proposed to explain greater α-KIEs; ,, (2) single-step α-KIEs > 1.08 are solvent independent;3b and (3) single-step α-KIEs > 1.08 are independent of the structure of the alkyl group of the substrate. 3b, …”

“…A major, long-term, research program has focused on studies of secondary deuterium kinetic isotope effects (α-, β-, and γ-) for solvolyses of primary and secondary alkyl substrates, − to probe reaction mechanisms without the more substantial perturbations of the reaction system which arise when substituent or solvent effects are investigated. Mechanistic explanations, usually based on a simplified version of the extended ion pair mechanism of Winstein (Scheme ), include the timing of rate-determining nucleophilic attack (on covalent substrate or on various ion pairs) 1 and the kinetic and stereochemical consequences of competing elimination reactions …”

“…Other assumptions or parameters refer to KIEs for individual steps;3b the most important (assumption 4) is the single-step α-KIE of 1.15 for k 1 (Scheme ), 3b,4e based initially on solvolyses of pinacolyl brosylate ( 3 , X = OBs), ,4g but later used for cyclopentyl substrates ( 6 ). 3b,4e Instead of a structural effect on α-KIE, additional mechanisms involving ion pair return are proposed to account for higher α-KIEs. ,,, However, a slightly higher α-KIE of 1.165 for solvolyses of 2,2-dimethyl-3-pentyl brosylate was attributed to “slightly enhanced steric congestion of the alpha CH bond in the initial state” 4h (i.e. even incorporation of one extra methyl group into 3 increases the α-KIE).…”