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Author Notes:

E-mail: Lanny S. Liebeskind, CHEMLL1@emory.edu. Djamaladdin G. Musaev, dmusaev@emory.edu.


Research Funding:

This research was supported by the National Science Foundation for DGM under the Center for Chemical Innovation in Stereoselective C–H Functionalization (CHE-0943980).

The authors gratefully acknowledge NSF MRI-R2 grant (CHE-0958205) and the use of the resources of the Cherry Emerson Center for Scientific Computation.

Mechanistic Insights into the Aerobic Copper(I)-Catalyzed Cross-Coupling of S -Acyl Thiosalicylamide Thiol Esters and Boronic Acids


Journal Title:



Volume 31, Number 22


, Pages 7958-7968

Type of Work:

Article | Post-print: After Peer Review


The Density Functional Theory (DFT) method is used to elucidate the nature of the active species and the mechanism of the aerobic CuI-catalyzed cross-coupling of S-acyl thiosalicylamide thiol esters and boronic acids reported previously (J. Am. Chem. Soc. 2007, 129, 15734–15735; Angew. Chem., Int. Ed. 2009, 48, 1417-1421). The energetically lowest isomer of the proposed active species [LC(O)R1]Cu-(O2)-Cu[LC(O)R1]2+, 2a, (where L = thiolatosalicylamide) is found to be I1(OO,OO) with a μ-η2:η2-peroxo Cu2O2-core, while its isomers I2(OO,OO) with a bis-(μ-O) Cu2O2-core and I3(OO,OO) with a (μ-η1:η1) Cu2O2-core lie only a few kcal/mol higher and separated by 4–7kcal/mol energy barriers. In all these isomers, the thiol ester is coordinated to the Cu-centers via its two O-ends. Isomers with (SO,OO) and (SO,SO) coordination modes of the thiol esters lie slightly higher and are separated with moderate energy barriers. We found the latter isomers to be vital for the reported CuI-templated cross-coupling of S-acyl thiosalicylamide thiol esters and boronic acids under aerobic conditions. The presence of an anion (halide, carboxylate modeled as formate) in the reaction medium is found to be necessary. Its coordination to the active catalyst I1(SO,SO) is the first step of the proposed anion-assisted transmetalation by boronic acid. Overall the transmetalation reaction requires 34.0 kcal/mol and is 24.0 kcal/mol exergonic. This conclusion is in reasonable agreement with available experiments. The C-C bond formation in the transmetalation product requires a 6.3 kcal/mol lower energy barrier and is highly exergonic.

Copyright information:

© 2012 American Chemical Society

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