162. Combined C−H Activation/Cope Rearrangement as a Strategic Reaction in Organic Synthesis:  Total Synthesis of (−)-Colombiasin A and (−)-Elisapterosin B

Authors: Huw M. L. Davies, Xing Dai , and Matthew S. Long

J. Am. Chem. Soc.,

2006, 128 (7), 2485–2490


The total synthesis of (−)-colombiasin A (2) and (−)-elisapterosin B (3) has been achieved. The key step is a C−H functionalization process, the combined C−H activation/Cope rearrangement, between methyl (E)-2-diazo-3-pentenoate and 1-methyl-1,2-dihydronaphthalenes. When the reaction is catalyzed by dirhodium tetrakis((R)-(N-dodecylbenzenesulfonyl)prolinate), Rh2(R-DOSP)4, an enantiomer differentiation step occurs where one enantiomer of the dihydronaphthalene undergoes the combined C−H activation/Cope rearrangement while the other undergoes cyclopropanation. This sequence controls the three key stereocenters in the natural products such that the remainder of the synthesis is feasible using standard chemistry.

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