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

The regio- and stereochemistry of the nucleophilic attack of ( S )- trans -3-hexen-2-ol ( M S ) and ( S )- trans -4-hexen-3-ol ( E S ) on the corresponding O-protonated (L = H) and -methylated (L = CH 3 ) derivatives ( M S L + and E S L + ) are investigated in the gas phase at 40 °C (720 Torr). The M S L + and E S L + intermediates are produced in the gas phase by the attack of the ionic Brønsted and Lewis acids, formed by stationary γ-radiolysis of bulk CH 3 Cl, on the corresponding chiral alcohols, i.e., M S and E S . In these systems, firm evidence in favor of the concerted S N 2‘ pathway, accompanying the classical S N 2 one, is obtained by excluding the following: (i) the isomerization of M S L + (or E S L + ) before the attack by the nucleophile NuH = M S (or E S ); (ii) the isomerization of the (C 6 H 11 ) 2 OH + substitution intermediates before neutralization; (iii) the intermediacy of allylic cations. The regioselectivity factors (S N 2‘/S N 2 = 1.4 ( M S ), 1.1 ( E S )) confirm previous experimental and theoretical evidence about the prevalence in the gas phase of the S N 2‘ pathway, over the competing S N 2 one. Orientation of NuH by M S L + (or E S L + ) determines the regiochemistry of the allylic substitution. When NuH approaches the oxonium intermediate from the direction syn to the leaving moiety LOH, a frontside S N 2 displacement takes places favored by preliminary proton bonding between LOH and NuH. The S N 2‘ reaction instead follows attack on the π-LUMO of the oxonium ion by the NuH juxtaposed anti to the leaving LOH group. Observation of a predominant anti -S N 2‘ orientation provides the first experimental basis of modern concepts pointing to Coulombic interactions as the main intrinsic factors governing the S N 2‘ stereochemistry and to solvation and ion pairing as the factors determining the low efficiency of S N 2‘ reactions and their preferred syn stereochemistry in solution.