Inter‐ and Intramolecular [2+2]‐Photocycloaddition of Tetronates − Stereoselectivity, Mechanism, Scope and Synthetic Applications

Abstract

Abstract[2+2]‐photocycloaddition reactions of various tetronates (3−8, 12, 16, 20, 37) have been examined. The tetronates were prepared from the corresponding tetronic acid by O‐alkylation with an alkyl bromide or with an alcohol (Mitsunobu protocol). If the photocycloaddition reaction (λ = 254 nm, solvent: diethyl ether or tert‐butyl alcohol) was carried out in an intramolecular fashion the tri‐ and tetracyclic products 21−23, 27−36 were obtained in good yields (52−75%) and with excellent simple diastereoselectivity. The reaction tolerates a high degree of substitution at both the tetronate and at the alkene double bond. High facial diastereoselectivities were observed if stereogenic centers were present in the alkene tether (e.g. 7a → 33) or if the alkenyl substituent was attached to the stereogenic C5 carbon atom of the tetronate irradiation precursor (e.g. 20 → 32). The reaction was also conducted in an intermolecular fashion. The methoxyethoxymethoxy (MEM) protecting group was suitable to protect the free tetronate hydroxy group. The photocycloaddition of tetronate 8 to cyclopentene was highly selective delivering the tricyclic products 39 in an 8:1 exo/endo ratio (59% yield). The products obtained from the intermolecular reaction underwent a de Mayo‐like ring expansion delivering oxepane‐diones 45−47 in good yields (74−84%). In mechanistic studies it was found that the formation of the photoproduct was supressed upon addition of piperylene. Furthermore, in the presence of acetone as a sensitizer the reaction could be conducted at λ = 300 nm. At this wavelength no conversion occurred under direct irradiation. These observations suggest the involvement of triplet intermediates in the reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)