Inversion versus Retention of Configuration for Nucleophilic Substitution at Vinylic Carbon

Abstract

A high-level computational study using CCSD, CCSD(T), and G2(+) levels of theory has shown that unactivated vinyl substrates such as vinyl chloride would afford gas phase, single-step halide exchange by a pure in-plane sigma-approach of the nucleophile to the backside of the C--Cl sigma bond. Geometry optimization by CCSD/6-31+G* and CCSD(T)/6-31+G* confirms the earlier findings of Glukhovtsev, Pross, and Radom that the S(N)2 reaction of Cl(-) with unactivated vinyl chloride in the gas phase occurs by a sigma attack. Complexation of vinyl chloride with Na(+) does not alter this in-plane sigma preference. However, moderately activated dihaloethylenes such as 1-chloro-1-fluoroethylene undergo gas-phase S(N)2 attack by the accepted pi-route where the nucleophile approaches perpendicular to the plane of the C==C. In the latter case a single-step pi pathway is preferred for the Cl(-) + H(2)C==CFCl reaction. This is the first definitive example at a high level of theory where a single-step pi nucleophilic vinylic substitution is preferred over a multistep mechanism in the gas phase. The activation barriers for these gas-phase single-step sigma- and pi-processes involving both naked anions and Na(+) complexes are, however, prohibitively high. Solvation and the presence of a counterion must play a dominant role in nucleophilic vinylic substitution reactions that proceed so readily in the condensed phase. In solution, nucleophilic vinylic substitution reactions involving electron-withdrawing groups on the carbon--carbon double bond (e.g., -CN, -CHO, and -NO(2)) would almost certainly proceed via a free discrete carbanionic intermediate in accord with experiment.

Synthesis and reactivity of heterocyclic hydroxylamine-O-sulfonates

“…To some extent, the electrophilic amination reactions of anions J (Scheme 8), K (Scheme 9), and M (Scheme 10) presented above resemble the previously investigated S N 2 reactions at sp 2 -hybridized carbon [57][58][59][60][61][62][63] or nitrogen [64] atoms, as well as the Boulton-Katritzky rearrangement [65,66]. Thus, the substitution of the sulfate leaving group by an amidate or thioamidate anion may proceed according to either the S N 2π mechanism (out-of-plane nucleophilic attack) by interacting with the π orbital of the imino group, or S N 2σ mechanism (in-plane attack) where a nucleophile interacts with the σ orbital of the imino nitrogen atom (Figure 9).…”

Transition-metal-free chemo- and regioselective vinylation of azaallyls

“…36–38 Both stepwise and concerted (S N V) 39–42 substitutions have been reported for vinyl halides, but not with carbon-derived anions. Mechanisms are case-dependent with the nature of the nucleophile, the leaving group, and the electrophile substitution pattern all playing a role.…”

“…DFT calculations did, however, reveal a concerted displacement with a low energetic barrier (11.7 kcal/mol) to deliver the vinylated product B1 with concomitant release of bromide (Figure 4). A strong kinetic preference (ΔΔG ‡ > 7 kcal/mol) for nucleophilic attack perpendicular to the carbon-carbon double bond (S N V) 39–42 at the less sterically encumbered β-position ( A1-B1-TS vs A1-C1-TS ) was found. Notably, both product regioisomers ( B1 and C1 ) are nearly isoenergetic.…”

“…For substrates lacking a β-aryl group, reaction is expected to slow according to both mechanisms, but to a far larger degree for the azaallyl anion mechanism. 39–42 As illustrated in Figure 2b, 1-bromo-2-methylprop-1-ene ( 2i ) and (bromomethylene)cyclohexane ( 2j ) underwent reaction, albeit more slowly (12 h) and with reduced yields (54 and 55%, respectively). Although there are well-documented errors associated with determining accurate quantitative barriers with charged species, computations employing the commonly used B3LYP functional, which has been used by others to study S N V reactions, predicted prohibitively high barriers (>36 kcal/mol) for the azaallyl anion A1 and 1-bromo-2-methylprop-1-ene in both gas-phase and in implicit solvent.…”

Fragmentations of (E)- and (Z)- isomers of 2-methylbuten-1-yl(aryl)iodonium triflates: competing mechanisms for enol triflate formation

“…8,9 This process leads to complete inversion at the α-carbon and is supported by computational studies using MP2 calculations with polarized double-zeta basis sets. …”