Abstract
We describe a powerful, broadly applicable cross-coupling protocol that enables carbon-carbon bond formation at highly sterically hindered carbon centers (both sp2 and sp3) by employing organocopper reagents under palladium catalysis. Experimental studies and theoretical calculations indicated that the key to the unique reactivity of copper is the relatively low activation energy of the compact transmetalation transition state, due to Cu(i)-Pd(ii) interaction, which is associated with small values of deformation energy of the reactants. This reaction is applicable to a variety of bulky substrates, including compounds inert to previous cross-coupling chemistry and has high functional group tolerance.
Highlights
Three-dimensionally (3D) bulky carbon frameworks and other bulky substrates have become important scaffolds for a broad range of functional molecules (Scheme 1A)
The crosscoupling reactions using a boronate ester or zinc(II) complex of 9-triptycene (1a and 1b) failed to afford any coupled product under the representative palladium-catalyzed conditions.7e,g,h On the other hand, we found that the crosscoupling reaction of 9-triptycenylcopper(I) complex 1c10 with 2 smoothly proceeded using 5 mol% of Pd(OAc)2 and tris(omethoxyphenyl)phosphine (L1) at 80 C to afford the coupling product 3 in 86% yield
The optimized conditions of the present organocopper crosscoupling reaction were applied to bond formation using a variety of electrophiles (Scheme 2A)
Summary
Three-dimensionally (3D) bulky carbon frameworks and other bulky substrates have become important scaffolds for a broad range of functional molecules (Scheme 1A). Recent improvements have focused mostly on the design of (pre)catalysts and customized ligands in order to achieve efficient generation of active palladium species, and on the oxidative addition/reductive elimination step in the catalytic cycle (Scheme 1B).6 These “state-of-the-art” systems, in particular with customized ligands, enable bond formation on sterically hindered substrates.7 transmetalation, a fundamental step in cross-coupling reactions,8 can be targeted to address this challenge.
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