page_title: Ene reaction
section_title: Concerted pathway and transition states
hierarchical_section_title: Ene reaction / Mechanism / Concerted pathway and transition states
caption_attribution_description: English: late TS
context_page_description: The ene reaction is a chemical reaction between an alkene with an allylic hydrogen and a compound containing a multiple bond, in order to form a new σ-bond with migration of the ene double bond and 1,5 hydrogen shift. The product is a substituted alkene with the double bond shifted to the allylic position.
  This transformation is a group transfer pericyclic reaction, and therefore, usually requires highly activated substrates and/or high temperatures. Nonetheless, the reaction is compatible with a wide variety of functional groups that can be appended to the ene and enophile moieties. Many useful Lewis acid-catalyzed ene reactions have been also developed, which can afford high yields and selectivities at significantly lower temperatures, making the ene reaction a useful C–C forming tool for the synthesis of complex molecules and natural products.
context_section_description: The main frontier-orbital interaction occurring in an ene reaction is between the HOMO of the ene and the LUMO of the enophile (Figure 2). The HOMO of the ene results from the combination of the pi-bonding orbital in the vinyl moiety and the C-H bonding orbital for the allylic H. Concerted, all-carbon-ene reactions have, in general, a high activation barrier, which was approximated at 138 kJ/mol in the case of propene and ethene, as computed at the M06-2X/def2-TZVPP level of theory. However, if the enophile becomes more polar (going from ethane to formaldehyde), its LUMO has a larger amplitude on C, yielding a better C–C overlap and a worse H–O one, determining the reaction to proceed in an asynchronous fashion. This translates into a lowering of the activation barrier until 61,5 kJ/mol (M06-2X/def2-TZVPP), if S replaces O on the enophile. By computationally examining both the activation barriers and the activation strains of several different ene reactions involving propene as the ene component, Fernandez and co-workers  have found that the barrier decreases along the enophiles in the order H₂C=CH₂ > H₂C=NH > H₂C=CH(COOCH₃) > H₂C=O > H₂C=PH > H₂C=S, as the reaction becomes more and more asynchronous and/or the activation strain decreases.
  The concerted nature of the ene process has been supported experimentally, and the reaction can be designated as [σ2ₛ + π2ₛ + π2ₛ] in the Woodward-Hoffmann notation. The early transition state proposed for the thermal ene reaction of propene with formaldehyde has an envelope conformation, with a C–O–H angle of 155°, as calculated at the 3-21G level of theory.
  Schnabel and co-workers have studied an uncatalyzed intramolecular carbonyl-ene reaction, which was used to prepare the cyclopentane fragment of natural and non-natural jatropha-5,12-dienes, members of a family of P-glycoprotein modulators. Their DFT calculations, at the B1B95/6-31G* level of theory for the reaction presented in Figure 3, propose that the reaction can proceed through one of two competing concerted and envelope-like transition states. The development of 1,3-transannular interactions in the disfavored transition state provides a good explanation for the selectivity of this process.
  The study of Lewis acid promoted carbonyl-ene reactions, such as aluminum-catalyzed glyoxylate-ene processes (Figure 4), prompted researchers to consider a chair-like conformation for the transition state of ene reactions which proceed with relatively late transition states. The advantage of such a model is the fact that steric parameters such as 1,3-diaxial and 1,2-diequatorial repulsions are easy to visualize, which allows for accurate predictions regarding the diastereoselectivity of many reactions.
caption: Figure 4. Chair-like transition state proposed for Lewis-acid catalyzed carbonyl-ene additions
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