New insights into the endo–exo stereoselectivity of the intramolecular Diels-Alder reaction of 1,3,8-nonatrienes

Allylic Stereocontrol of the Intramolecular Diels–Alder Reaction

“…No π‐diastereofacial selectivity was witnessed in cyclization of either maleate 3 x or fumarate 3 y , however, indicating that a lone homoallylic stereocenter is insufficient to invoke stereoselection. It is noteworthy that the ( E )‐dienophile precursor 3 x undergoes a trans ‐selective IMDA reaction, a result which is consistent with previous findings4, 7, 10, 31, 32 but in contrast to those of the other three fumarate precursors in the present study.…”

“…The same isolated yields and stereochemical outcomes28 were obtained when 1 f was heated in toluene or chlorobenzene, although the former required prolonged reaction times for complete conversion. Fumarate 1 f underwent cycloaddition with virtually complete unlike ‐selectivity and high cis ‐selectivity, the latter feature being in stark contrast to previous findings with pentadienyl fumarates, which generally furnish mildly trans ‐selective IMDA reactions 4. 7, 10, 31, 32…”

“…In recent times, transition structures (TSs) for certain IMDA reactions have been located by using density functional theory (DFT). With reference to these TS geometries, cis/trans and π‐facial selectivities of IMDA reactions have been discussed in detail 4–10. This approach promises to greatly simplify the prediction of IMDA stereoselectivities.…”

“…To shed light upon stereoselectivities, these reactions are examined computationally by using the hybrid B3 LYP functional together with the 6–31G(d) basis set. It is generally accepted that B3 LYP/6–31G(d) models give reliable geometries of TSs and activation energies for pericyclic reactions 4–10. 18…”

The Diels-Alder reaction: an update

“…The Houk and Clark Still groups have investigated the IMDA reactions of 1,3,8-nonatriene, 1,3,9-decatriene and 1,3,10-undecatriene with regard to stereoselectivities, activation parameters and modelling of the transition state 47 (Scheme 11; equation 1). The related esters (Scheme 11; equation 2) have been studied 48,49 both experimentally and theoretically with regard to endo and exo transition states and their asynchronous nature, in which the internal carboncarbon bond is more developed than the peripheral carboncarbon bond. The influence of diene geometry has been determined experimentally 50 for the case of trienes separated by a simple trimethylene chain (Scheme 11; equation 3), with Lewis acid catalysis being able to alter substantially the stereoselectivity from that observed under thermal conditions.…”