Double Diels−Alder Reactions of Linear Conjugated Tetraenes

[reaction: see text] Linear conjugated tetraenes are shown to participate effectively as bis-dienes in sequences involving either two intermolecular Diels-Alder reactions or an intramolecular followed by an intermolecular Diels-Alder reaction. Thus, simple tetraenol 1 is transformed into tetracyclic products 5, 6, and 9 in high yielding and highly stereoselective sequences with maleic anhydride involving the formation of three rings, four C-C bonds and one C-O bond, and eight stereocenters. In the latter case, the one-pot reaction protocol is very simple, and furnishes a single diastereoisomeric product in essentially quantitative yield. Linear conjugated tetraenes exhibit complete terminal site selectivity in reactions with dienophiles and computational investigations reveal that two discrete pi-conjugative interactions are the origin of this unexpected reactivity. B3LYP/6-31G(d) transition structures also allow an explanation of unexpectedly high pi-diastereofacial selectivities witnessed during these transformations, through the identification of preferred C1-C diene conformations and nonbonded interactions. These new experimental and computational findings encourage the use of linear conjugated polyenes in domino sequences.