Catalytic palladium-oxyallyl cycloaddition

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Science  02 Nov 2018:
Vol. 362, Issue 6414, pp. 564-568
DOI: 10.1126/science.aau4821

Steps to smaller rings

Certain ring-forming reactions in organic chemistry are efficient because the orbital symmetries match up in the reactants and products. Oxyallyl ions tend to react with dienes in this paradigm to form seven-membered rings. Under palladium catalysis, Trost et al. redirected this reaction toward more common five-membered tetrahydrofuran rings by appending an ester to the diene. Although that pathway is symmetry-forbidden, the electron-withdrawing ester appears to stabilize a key intermediate along a stepwise route to the smaller ring.

Science, this issue p. 564


Exploration of intermediates that enable chemoselective cycloaddition reactions and expeditious construction of fused- or bridged-ring systems is a continuous challenge for organic synthesis. As an intermediate of interest, the oxyallyl cation has been harnessed to synthesize architectures containing seven-membered rings via (4+3) cycloaddition. However, its potential to access five-membered skeletons is underdeveloped, largely due to the thermally forbidden (3+2) pathway. Here, the combination of a tailored precursor and a Pd(0) catalyst generates a Pd-oxyallyl intermediate that cyclizes with conjugated dienes to produce a diverse array of tetrahydrofuran skeletons. The cycloaddition overrides conventional (4+3) selectivity by proceeding through a stepwise pathway involving a Pd-allyl transfer and ring closure sequence. Subsequent treatment of the (3+2) adducts with a palladium catalyst converts the heterocycles to the carbocyclic cyclopentanones.

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