Fig. 4

(a) Proposed mechanism for Au(III)-promoted amide cleavage (single-release) from model substrate B′. (b) Minimum energy pathways (MEP) calculated with SMD(H2O)/M06/6-311G(d,p)+SDD(Au) for the amide cleavage (single-release) from model substrate B′ catalyzed by Na[AuCl4] in water. The complete low-energy 5-exo-trig cyclization pathway (in blue) was computed, including all postulated intermediates, while only key transition states and intermediates for the more energetic (i.e., less stable) 6-endo-trig pathway (in orange) were calculated for comparison. The intrinsic activation barriers of the chemically relevant steps are labeled with their associated intrinsic rate constants (kcyc: cyclization; khyd: hydration; krel: amide release). When two chiral centers are generated, only the most stable diastereomer is discussed, irrespective of its absolute configuration. Breaking/forming bonds are represented with green dotted lines. Distances are given in angstrom. Free energies are given in units of kcal mol–1. Asterisks denote steps in which external species such as Na[AuCl4], NaCl, neutral and protonated water clusters, etc., enter or leave the main reaction (see Figure S25 for a more complete depiction); given the intrinsic inaccuracy of calculating the energetics of such hypothetical equilibria, relative energies of charged/neutral species and thus the global thermodynamics of the process should be considered with caution. c, Proposed mechanism for Au(III)-promoted amide and allyl leaving group decaging (dual-release) from model substrate H′ (see Figure S26 for a more complete depiction). The optimized structures of chemically relevant transition states are shown as ball-and-stick models.