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Stereoselectivity Control by Oxaspiro Rings during Diels−Alder Cycloadditions to Cross-Conjugated Cyclohexadienones:  The Syn Oxygen Phenomenon

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journal contribution
posted on 29.12.2004, 00:00 by Katsuo Ohkata, Yukiko Tamura, Brandon B. Shetuni, Ryukichi Takagi, Wataru Miyanaga, Satoshi Kojima, Leo A. Paquette
The diastereofacial selectivity operating in Diels−Alder additions involving spirocyclic cross-conjugated cyclohexadienones with dienes of varying reactivity has been investigated. The study has included the ether series 1ac as well as the lactone/ketone pair 2a/2b. In all cases, the preferred [4+2] cycloaddition pathway consisted of bonding from that π-surface syn to the oxygen atom. 4-Substituted-4-methyl-2,5-cyclohexadienones (monocyclic systems) were also examined and found to undergo bond formation preferentially from the face bearing the more electron-withdrawing of the two groups at the 4 position. Kinetic parameters were determined for the cycloaddition of 1a and 2a to cyclopentadiene. The rate acceleration profile of solvents was in the order CF3CH2OH ≫ CH3CN∼CH2Cl2 for the production of 9a from 1a and CF3CH2OH ≫ CH2Cl2 > CH3CN for the production of 21a from 2a, respectively. This spread in polarity had no major impact on product distribution, a phenomenon also reflected in the behavior of 4-substituted-4-methyl-2,5-cyclohexadienones under comparable conditions. Theoretical assessment of these experimental facts was undertaken at the HF/6-31G* level. The facial selectivity is understandable in terms of the secondary interaction between the HOMO of the diene and LUMO of the dienophile as well as the effective hyperconjugation between the newly forming bond and the 4-anti-C−C σ-orbital due to the more electron-donating bond, as defined by the Cieplak model.