Gas‐Phase Acid‐Induced S_N2′ versus S_N2 Mechanism in Allylic Alcohols

Abstract

A first demonstration of the existence of the concerted SN2' mechanism in the gas phase was obtained by establishing the regioselectivity of the attack of a neutral nucleophile, such as MeOH, on several allylic oxonium ions. These were generated in the gas phase by the reaction of radiolytically formed GA' acids (GA+ = C,H: (n = I , 2), iC,H:, and (CH,),F+) with trans-(1) and cis-2-buten-1-01 (2) as well as with I-buten-3-01 (3). Firm evidence in favor of the concerted SN2' pathway accompanying the classical SN2 one in these systems was obtained after careful evaluation of the extent of conceivable intramolecular isomerization both of the primary oxonium ions from GA' attack on 1-3 before nucleophilic displacement by MeOH and of their substituted intermediates before neutralization. The intermediacy of free allylic ions in the nucleophilic substitution was ruled out by generating the ions by protonation of 1,3-butadiene and by investigating their behavior in exactly the same media employed in the substitution reactions. The regioselectivity of MeOH with the ionic substrates investigated showed the occurrence of nearly equally extensive SN2' and SN2 pathways in the oxonium ions from 1 (SN2' (57f2%) and SN2 (43 2 YO)) and 3 (SN2' (54 + 2 YO) and SN2 (46+2%)), whereas, with 2, the SN2 (66 2 YO) reaction prevailed over the SN2' one (34 2 %). The role of intrinsic structural factors in determining the SN2'/SN2 branching in the selected oxonium ions is discussed.

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

“…Accordingly, the figures in Table reveal that, in the gas phase, nucleophilic substitution by M S (or E S ) on M S L + (or E S L + ) (L = H, CH 3 ) proceeds by a concerted S N 2‘ mechanism (58%, with M S ; 52%, with E S ) slightly prevailing over the classical S N 2 reaction (42%, with M S ; 48%, with E S ). This regioselectivity compares well with that measured in the acid-promoted nucleophilic substitution by CH 3 OH on strictly related allylic alcohols (54−57% S N 2‘; 43−46% S N 2) under comparable experimental conditions . Besides, in all cases investigated, the S N 2 reaction predominantly proceeds via retention of the configuration of the C α center (α r /α i = 2.1, with M S ; 4.2, with E S ), whereas the S N 2‘ reaction displays a distinct anti stereoselectivity (γ a /γ s = 3.4, with M S ; 5.5, with E S ).…”

“…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.…”

“…[23][24][25][26] 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. [27][28][29] The same modern concepts consider restrictive any theoretical rationale of the S N 2′ stereochemistry simply based on stereoelectronic factors, [30][31][32][33][34][35][36][37][38][39][40] since an important role may be played by Coulombic interactions between NuH and LG and among these and the reaction medium.…”

10 Gas phase organic ion–molecule reaction chemistry

“…However, unusually high yields of retention products have been observed in previous studies of gas phase, cationic S N 2 processes. 55,56…”

Stereoselectivity in the collision-activated reactions of gas phase salt complexes

“…In general, these processes have been probed in the condensed phase, but there is no reason why mass spectrometry could not also be used to screen gas phase reactions for stereoselectivity [35,36]. An advantage of this approach is that in the solvent-free environment of the gas phase, it is possible to gain a clear understanding of the molecular interactions that lead to stereoselectivity in a chemical transformation.…”