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A general working model mechanism is represented in Scheme?4. The study reported here considers the starting material to be a zwitterionic iminium formed after condensation of dimethylamine with salicylaldehyde. It was previously reported that coordination of the boron species to the phenoxide was energetically more favoured than coordination with the phenol moiety.[15],?[33] buy Everolimus Hence, the activation of the glycerol boronic ester by the phenoxy group to form the ��ate complex�� was also considered presumed? to be the earliest step of this reaction. A decrease in both electronic and free energies for the ate complex formation was determined, demonstrating the stabilisation of the species by interaction of the zwitterionic iminium and the boron species through B?O bond formation, and corroborated by the 0.5�C0.6?Wiberg indices (WI) determined for the B?O bond in ATE1 and ATE2. The stabilisation of the six-membered ring ate complex ATE1 is higher than the stabilisation of ATE2 by 4?kcal?mol?1 when compared with the initial set of reagents. Inspection of the conformations of the ate complexes reveals the tetrahedral character of the boron atom, forcing the Palbociclib in vitro five-membered cyclic boronate ester moiety to adopt a puckered conformation in ATE2 and a chair conformation in ATE1. Figure 1 Free-energy profiles calculated for the Petasis reaction between dimethylamine, salicylaldehyde, and glycerol 1,2-phenylboronate (solid lines) or glycerol 1,3-phenylboronate (dashed lines). The geometries optimised for the reactions are presented. The ... Scheme 4 Petasis borono�CMannich (PBM) reaction with glycerol-derived boronic esters. Relative energies given in parenthesis (in kcal?mol?1) refer to the optimised, zwitterionic 2-[dimethyliminio)methyl]phenolate (Im) and glycerol 1,2-phenylboronate ... In the determined energy profile, the ate complex needs to adopt a different conformation, placing the migratory substituent closer to the sp2 carbon of the iminium. Such conformations (ATE1�� and ATE2��) are only Cofactor difference between TS1 and TS2, and the energy barrier totals 20.2?kcal?mol?1 for TS1 and 18.1?kcal?mol?1 for TS2. The transition states obtained have similar features, with intermediate geometries between the second conformation of the ate complex (ATE1�� and ATE2��) and the tertiary amines (TA1 and TA2). In both cases, it is clear that the B?C(Ph) boron bond is being broken (d=1.71??, WI=0.54 for TS1 and d=1.47??, WI=0.65 for TS2), whilst a new C?C(Ph) bond is starting to form (d=1.97??, WI=0.49 for TS1 and d=2.00??, WI=0.46 for TS2).