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

The density functional theory method is used to elucidate the nature of the active species and the mechanism of the aerobic Cu-I-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)R-1]Cu-(O-2)-Cu[LC(O)R-1](2+), 2a (where L = thiolatosalicylamide), is found to be I1((OO,OO)), with a mu-eta(2):eta(2)-peroxo Cu2O2 core, while its isomers I2((OO,OO)), with a bis(mu-O) Cu2O2 core, and I3((OO,OO)), with a (mu-eta(1):eta(1)) Cu2O2 core, lie only a few kcal/mol higher and are separated by 4-7 kcal/mol 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 repotted Cu-I-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.