Table 3 Substrate scope of the ATH reaction with ligand 13f?
Related Figures (11)
Scheme 1. Proline-derived chiral triazole-based ligands. As a benchmark reaction for initially testing the chiral aminotriazole ligands, we chose the ruthenium- catalyzed transfer hydrogenation of ketones. This re- action has been extensively studied in the last two de- cades, since the groundbreaking work by Noyori on the use of ruthenium-arene complexes with mono- Figure 1. Triazole-based ligands used in catalysis. as ligands for Pd-catalyzed allylic alkylation reactions and tetradentate bis(triazolylamines) (4) for Mn-cata- lyzed epoxidation reactions."*! In some cases, direct coordination of either the N-2 or N-3 nitrogen atoms of the triazole group to the metal was demonstrated by different means including X-ray crystallographic analysis, as in the case of tristriazole-copper!'®! and phosphinito-triazole-rhodium"*! complexes. Enantio- selective applications, however, remain completely unexplored. Figure 2. General structure and catalytic cycle of Noyori- type catalysts for transfer hydrogenation. With this in mind, aminotriazole ligands 5 and 6 (Scheme 1) were expected to form chelate complexes with ruthenium coordinated to the triazole moiety through different nitrogen atoms (Figure 3), both likely to be active as catalysts for the transfer hydro- genation of ketones. Figure 3. Putative ruthenium(II) complexes with chiral ami- notriazole ligands 5 and 6. Scheme 3. ATH of acetophenone with ligands 5 and 6. Scheme 4. One-pot preparation of hydroxyalkyne 11a. With this alkyne in hand, introduction of different substituents on the hydroxy group, by well known protecting group chemistry allowed preparation of various ether and silyl ether derivatives 11b-f. Cu-cat- alyzed cycloaddition with trimethylsilyl azide, fol- lowed by deprotection, led uneventfully to the target ligands 13a-f (Scheme 5).!**! Although both ligands represented active catalysts for the reaction, the results made apparent the superi- ority of ligand 6, bearing a free triazole NH group. Although the use of neutral ligands in this reaction (giving place to cationic ruthenium catalysts) has been described, it is worth noting that the vast majori- ty of the successful ligands in this kind of systems act as anionic ones (giving place to neutral catalysts). Scheme 2. Preparation of proline-derived chiral aminotriazole ligands 5 and 6. Scheme 5. Preparation of the family of ligands 13a-f. Table 2. Effect of base, arene ligand and metal to ligand ratio in the ATH of acetophenone with ligand 13f." Table 3. (Continued) n Gaussian 09.”*! The SDD basis set, including SDD artesian pseudopotentials for the ruthenium atom, vas employed. Figure 4. DFT calculated reaction profile for the ruthenium-catalyzed ATH of chromanone (9k) with ligand 13b Figure 5. DFT calculated transition states for the ruthenium-catalyzed ATH of chromanone (9k) with ligand 13b; top left: (Spu»Sy)-pro-R; top right: (Sp,,Sy)-pro-S; bottom left: (Rr,,Ry)-pro-S; bottom right: (Rp,,Ry)-pro-R.
