readily through a retro-ene mechanism to give allene products and nitrogen gas (see Myers allene synthesis). Mechanism Concerted pathway and transition states 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 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