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

Abstract

The Density Functional Theory (DFT) 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)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 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.

Figure 1

Calculated important transition states of the formate-assisted transmetalation in 2a by boronic acid and the C-C bond cross-coupling reactions. Here, we also present the atomic notations used in this paper.

Scheme 1

The proposed mechanism of the Cu^I-templated aerobic cross-coupling of thioorganic and boronic (see Ref. 5)

Scheme 2

Three possible O₂-coordination modes in Cu₂O₂-cores

Scheme 3

Model of species 2, as 2a, used in this paper

Scheme 4

Calculated isomers of 2a and connecting transition states (in dashed boxes) studied in this paper. Mulliken spin densities (in |e|) are given with each structure. Values in red and blue are for triplet and singlet electronic states of the reported structures, respectively.

Scheme 5

Calculated relative energies ( ΔH(ΔG)[ΔG_solv] in kcal/mol) of various isomers of 2a and connecting transition states. Values in red and blue are for triplet and singlet electronic states of the reported structures, respectively.

Scheme 6

Schematic presentation of located important reactants, intermediates, transition states and products of formate-assisted transmetalation in 2a by boronic acid and C-C bond cross-coupling reactions. For structures of the presented transition states see Figure 1. Full geometry parameters for all of these structures are given in the Supporting Information. Their important geometry parameters are given in Table 3.

Scheme 7

Calculated potential energy surface of the formate-assisted transmetalation in 2a by boronic acid and the subsequent C-C bond cross-coupling reactions. Presented energies are Gibbs free energies in solution (in kcal/mol). For notation of the structures, see Scheme 5 and Figure 1.