Pericyclic — [2,3]-sigmatropic
Mislow-Evans rearrangement
How the Mislow-Evans rearrangement works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Allylic sulfoxide; thiophile (P(OMe)₃, PhSH, or Et₂NH). Conditions: THF or MeOH, –20 to 25 °C. Bonds formed: C–O; shifted C=C; bonds broken: C–S; old C=C π (shifts). Stereochemistry: Suprafacial [2,3]; chirality transfer from S to C; E-alkene favored. Rate and selectivity: Equilibrium lies on sulfoxide; thiophile trapping pulls it forward.
At a glance
Step 1: Sulfoxide ⇌ sulfenate equilibrium
An allylic sulfoxide and an allylic sulfenate ester exist in a rapid equilibrium, interconverting through a [2,3]-sigmatropic rearrangement — a five-atom, closed-loop pericyclic shift, one atom shorter than the [3,3] shifts of Claisen and Cope.
Step 2: Five-membered cyclic transition state
Three curved arrows move through this five-membered cyclic transition state: the allylic S–C bond breaks, the allylic double bond shifts position, and the oxygen lone pair forms a new O–C bond at the far allylic terminus, all concertedly.
Step 3: Thiophile traps the sulfenate
Because the sulfenate ester is far more easily reduced (by a thiophile like a phosphine) than the sulfoxide, trapping that side of the equilibrium pulls the whole system toward the rearranged allylic alcohol — a mild, stereospecific way to transpose an allylic sulfoxide's position.
Abbreviations and terms
- Ph
- Phenyl. –C₆H₅.
- OMe
- Methoxy. –OCH₃.
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- MeOH
- Methanol. Polar protic solvent (also a nucleophile in solvolysis).
How it compares with related reactions
| Mislow-Evans rearrangement | Claisen rearrangement | Cope rearrangement of 1,5-hexadiene | |
|---|---|---|---|
| Reagents | Allylic sulfoxide; thiophile (P(OMe)₃, PhSH, or Et₂NH) | Allyl vinyl ether (e.g. from allyl alcohol + enol ether, or Johnson–Claisen) | 1,5-Hexadiene (and substituted analogues) |
| Conditions | THF or MeOH, –20 to 25 °C | Heat, 100–200 °C, no catalyst | Heat, ≈ 150–260 °C; or Pd(II) catalysis |
| Stereochemistry | Suprafacial [2,3]; chirality transfer from S to C; E-alkene favored | Chair TS; suprafacial; chirality transfer | Chair TS; suprafacial; E/Z-selective |
| Rate / selectivity | Equilibrium lies on sulfoxide; thiophile trapping pulls it forward | Concerted [3,3]; accelerated by polar solvents; driven by strong C=O | Degenerate here; ΔG° = 0, driven by substituents in general |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Mislow-Evans rearrangement?
Allylic sulfoxide; thiophile (P(OMe)₃, PhSH, or Et₂NH). Conditions: THF or MeOH, –20 to 25 °C.
Which bonds are formed and which are broken?
Formed: C–O; shifted C=C. Broken: C–S; old C=C π (shifts).
What is the stereochemical outcome?
Suprafacial [2,3]; chirality transfer from S to C; E-alkene favored
What controls the rate or the selectivity?
Equilibrium lies on sulfoxide; thiophile trapping pulls it forward
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti