Chemistry

Four Different Corners

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Science  06 Jul 2012:
Vol. 337, Issue 6090, pp. 15
DOI: 10.1126/science.337.6090.15-a

Photochemical dimerization of olefins can yield a wide variety of symmetrically substituted cyclobutane derivatives. The bigger challenge is generating a carbon square with a different substituent at each corner. Two different olefins can pair up with each other in multiple distinct combinations and orientations, risking a messy mixture. Yet nature appeared to have overcome the obstacles in a class of compounds isolated recently from the plants that produce black pepper. Two studies demonstrate complementary synthetic routes to these tetrasubstituted cyclobutanes. Gutekunst et al. used photochemistry at the outset, but in an intramolecular context, to bias the relative olefin orientations and set two distinct opposing corners. This left unsubstituted CH2 centers at the remaining corners, and the authors applied direct palladium-catalyzed vinyl and aryl iodide additions to establish the basic skeleton before functional elaborations. Liu et al. skirted photochemistry altogether, setting three corners by expanding a triangular cyclopropane precursor outward to a pendant carbene center. This yielded a cyclobutene poised for rhodium-catalyzed conjugate addition of an arylboronic acid to set the final corner. Close comparison of these products to the natural isolate revealed that the pepper plant was actually synthesizing an isomer with a six-membered (rather than four-membered) ring.

Angew. Chem. Int. Ed. 51, 10.1002/anie.201203897; 10.1002/anie.201203379 (2012).

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