Regioselectivity in the Gas‐Phase Nucleophilic Attack on O‐Protonated 3‐Methyl‐2‐cyclohexen‐1‐ol and 1‐Methyl‐2‐cyclohexen‐1‐ol

Abstract

Our radiolytic study of the occurrence in the gas phase of concerted SN2' reactions on several open-chain allylic oxonium ions generated in the gas phase from the attack of gaseous GA+ acids (GA' = C , H i ( n = l , 2), iC,H:, and (CH,),F+) on suitable substrates is now continued with cyclic allylic alcohols, such as 3-methyl-2-cyclohexen-1-01 (1) and 1-methyl-2-cyclohexen-1-01 (2), with both MeOH and NMe, as neutral nucleophiles. With MeOH as the nucleophile, the substitution reaction exclusively takes place on 1 as the starting compound, whereas when the substrate is 2 it is accompanied by extensive elimination. With NMe,, only the elimination reaction is observed in the same systems. The analysis of the isomeric distribution of the substitution and elimination products allows definition of the corresponding reaction patterns. As for open-chain oxonium ions, the nucleophilic attack on O-protonated 1 and 2 is preceded by significant intramolecular interconversion. Partial unimolecular dissociation of the same ionic intermediates also takes place. After careful evaluation of the extent of these side processes, it is demonstrated that the 0-protonated 1 undergoes the concerted S,2 process with MeOH almost exclusively (> 99 %). With 0-protonated 2, however, the concerted SN2' pathway (84-95%) prevails over the classical S J one (6-17%). Concomitant [1,2] (E2) and [1,4] elimination (E 2') pathways involve attack of the selected nucleophiles on the oxonium ions from 1 and 2. Their relative extent (E2'/E2:1.78-1.96 (1); 1.43-1.70 (2)) appears only slightly dependent on the nature of the ionic substrate, the nucleophile (whether MeOH or NMe,), and the leaving group (whether H,O or MeOH). The effects of both intrinsic structural factors and experimental conditions in determining the SN2'/SN2 and E2'1 E 2 branchings in the selected oxonium ions is discussed and compared with related gas-phase data.

Mass Spectrometric Studies of Organic Ion/Molecule Reactions

“…Amines were used as the nucleophiles, and not surprisingly, the amount of elimination increases as more basic amines are used. Finally, Speranza and co-workers − have recently used their radiolytic method to study the competition between S N 2 and S N 2‘ reactions in the acid-induced substitutions of allylic alcohols. The results show that S N 2‘ reactions can compete successfully with S N 2 reactions in these systems.…”

Chiral Ions in the Gas Phase. 1. Intramolecular Racemization and Isomerization of O-Protonated (S)-trans-4-Hexen-3-ol

“…The isomeric hexadienes of Table may as well arise in part from (MeO) 3 PO-induced bimolecular E2 and E2‘ elimination in IS or in its ionic isomers. However, the conceivable interference from these bimolecular elimination processes does not affect the estimate of the rate constants of Table , provided that they occur to the same extent irrespective of the specific isomer (cf., ref c). In this case, in fact, occurrence of bimolecular E2 and E2‘ eliminations may affect the absolute yields of the racemization and isomerization products, but not their relative distribution.…”

“…The study was stimulated from a recent gas phase investigation of the mechanism of acid-induced nucleophilic substitution on some allylic alcohols using radiolytic methods . It was demonstrated that the reaction proceeds through the concerted S N 2‘ pathway (eq ii of Scheme ), in competition with the classical S N 2 one (eq i of Scheme ).…”

“…Unequivocal evidence for these mechanisms was achieved only after careful weighing of the unimolecular processes which normally accompany bimolecular allylic substitution in solution, namely unimolecular dissociation (S N 1, eq iii of Scheme ) and intramolecular isomerization of the involved allylic oxonium intermediates (S N i‘, eq iv of Scheme ). For instance, in 760 Torr of CH 4 at 37.5 °C, up to 12% of intramolecular interconversion (eq iv of Scheme ) was observed in the oxonium intermediates with R/R‘ = H/Me, trans -Me/H, and cis -Me/H prior to substitution by methanol. 3a,b Under the same conditions, 11% is the maximum extent of interconversion observed prior to nucleophilic attack in the fraction (≥81%) of oxonium intermediates from protonation of 1-methyl-2-cyclohexen-1-ol and 3-methyl-2-cyclohexen-1-ol surviving unimolecular fragmentation 3c 1 …”

Regio- and Stereochemistry of Gas-Phase Acid-Induced Nucleophilic Substitutions on Chiral Allylic Alcohols1

“…Carrion and Dewar suggest that the predominance in solution of the S N 2 mechanism over the S N 2‘ one is primarily due to energy-demanding ion desolvation in the S N 2‘ transition structure, which mostly contributes to the building up of the relevant activation barrier, whereas the more favored S N 2 barrier is essentially determined by electronic factors. In light of these modern concepts, these and other authors conclude that there is no real reason concerted S N 2‘ reaction should not be feasible in the gas phase. − This indication has been followed in a recent gas-phase study of acid-induced nucleophilic substitution on some allylic alcohols that showed that the concerted S N 2‘ reaction actually competes with the classical S N 2 pathway in the absence of solvation and ion-pairing factors. − The same modern concepts consider restrictive any theoretical rationale of the S N 2‘ stereochemistry simply based on stereoelectronic factors, − since an important role may be played by Coulombic interactions between NuH and LG and among these and the reaction medium.…”