Isotope Effects, Dynamic Matching, and Solvent Dynamics in a Wittig Reaction. Betaines as Bypassed Intermediates

Abstract

The mechanism of the Wittig reaction of anisaldehyde with a stabilized ylide was studied by a combination of 13C kinetic isotope effects, conventional calculations, and molecular dynamics calculations in a cluster of 53 THF molecules. The isotope effects support a cycloaddition mechanism involving two sequential transition states associated with separate C–C and P–O bond formations. However, the betaine structure in between the two transition states is bypassed as an equilibrated intermediate in most trajectories. The role of the dynamics of solvent equilibration in the nature of mechanistic intermediates is discussed.

The Dynamics of Chemical Reactions: Atomistic Visualizations of Organic Reactions, and Homage to van ’t Hoff

“…Similara pproaches have been proposed previously by Hase [116] andD oubleday, [117] Chandler, [118] Glowacki, [119] and Singleton. [120] Our approach integrates conformational sampling for solvent molecules and quasiclassicals ampling forr eacting molecules, inspired originally from Truhlar and Gao's ensemble average-variational transition state theory (EA-VTST) approach. [121] SPTSS method has been applied to probe the dynamicalp rocess of water-accelerated Diels-Alder reactions.…”

Reductive Carbocyclization of Homoallylic Alcohols to syn‐Cyclobutanes by a Boron‐Catalyzed Dual Ring‐Closing Pathway

“…From A-TS-B,the reaction affords the cyclopropane B,which is energetically downhill by À5.9 kcal mol À1 .H owever,w ith the given energy landscape,there is avery shallow minimum for B that is presumed to result in some portion of activated molecules at the transition state to directly proceed to the intermediate C,not via intermediate B. [21] Starting from intermediate B,t he reaction may proceed through either intermolecular hydridation to form cyclopropane product E or intramolecular ring expansion to generate cyclobutane intermediate C.T he barriers for both possibilities are too low at 5.6 and 3.8 kcal mol À1 ,respectively, to infer any significant difference in the rate of these steps.It is an intermolecular process for the hydridation to proceed as shown on the left-hand side of Figure 1, whereas the ring expansion shown on the right-hand side is an entropically beneficial intramolecular event. Therefore, C at À10.4 kcal mol À1 should be formed exclusively.T he intermediate C may then be attacked by ab orohydride to give the product D, traversing another low barrier of 5.4 kcal mol À1 .H ydridation from the top is estimated to be preferred by approximately 3kcal mol À1 over the bottom-side attack to give the synselective product D.…”

Phosphonium salts and P-ylides

“…274 The mechanism of the Wittig reaction of anisaldehyde with a stabilized ylide was studied by Singleton and coworkers. 275 A combination of 13 C kinetic isotope effects, conventional calculations, and molecular dynamics calculations in a cluster of 53 THF molecules was considered, in order to establish if the reaction proceeds through a concerted or a two-step processes. The authors concluded that even if the isotope effects supported the formation of a betaine intermediate, nonetheless energetically perfect calculations employing any of the standard equilibrium methods cannot unambiguously assign mechanisms.…”