Schmittel cyclization

What is Schmittel cyclization?

In 1995, Schmittel et al. and Gillmann et al. independently reported the first instance of the intramolecular C2-C6 cyclization of hepta-1,2,4-triene-6-yne (i.e., enyneallene) to form a five-membered cyclic structure via a methyl fulvene biradical intermediate.

Schmittel cyclization - general reaction scheme - Schmittel reaction - Schmittel ring closure reaction
Schmittel cyclization
  • R1 = aryl, t-Bu, TMS, etc.
  • R2 = P(O)Ph2, alkyl, aryl, H
  • R3 = H, alkyl, aryl (see list of acronyms)

This reaction, known as the Schmittel cyclization, or occasionally the Schmittel reaction or Schmittel ring closure reaction, was previously thought to result in aromatic compounds, i.e., the Myers-Saito cyclization, before its discovery.

Theoretical studies show that the Myers-Saito cyclization is favored over the Schmittel cyclization by 25 Kcal/mol due to the attainment of aromaticity in the former. The Schmittel cyclization proceeds via a π-radical intermediate with a slightly alternating single and double bond, which makes it endothermic at ∼10 Kcal/mol and has an activation barrier of 35 Kcal/mol. However, enyne-allenes with an aryl group at the alkynyl terminus, benzannulation with enyne-allenes, or sterically bulky groups at the alkynyl terminus can easily undergo the Schmittel cyclization.

Benzannulation lowers the reaction barrier for the Schmittel cyclization from 30 to 25.2 Kcal/mol, whereas it only lowers the activation energy by ∼1.2 Kcal/mol for the corresponding Myers-Saito cyclization. The formation of a strong sp2-sp2σ bond from sp-hybridized carbons and the oxyanion substitute of enyne-allene are attributed to the occurrence of the Schmittel cyclization. Furthermore, oxyanion substitute of enyne-allene can switch the preferences of product formation from a biradical to a polar closed-shell singlet, and this effect is more pronounced for the Schmittel cyclization.