Ir-Catalyzed Borylation of CH Bonds in N-Containing Heterocycles: Regioselectivity in the Synthesis of Heteroaryl Boronate Esters

摘要

Aryl and heteroaryl boronates are very important, especially as intermediates for Suzuki-Miyaura cross-coupling reactions;[1] for the Cu-catalyzed CO and CN coupling reactions developed by Chan, Lam, and co-workers;[2] and for Rh-catalyzed conjugate additions to carbonyl compounds.[3] The most attractive potential synthesis of these boronate esters would be the direct borylation of CH bonds in arenes or heteroarenes themselves. A very exciting recent advance has been the development by Ishiyama et al.[4] and Smith and co-workers[5] of in situ prepared, suitably ligated analogues of the iridium tris(boryl) complexes discovered by us,[6] which catalyze the borylation of aromatic CH bonds under mild conditions. Density functional theory (DFT) calculations by Sakaki and co-workers,[7] in agreement with proposals from the experimental data, suggest that the key catalytic intermediate that leads to CH activation is the sterically encumbered, five-coordinate [Ir(Bpin)3L2] species (Bpin=B(OCMe2CMe2O)). This intermediate accounts for the selectivity observed, as borylation typically avoids positions ortho to either substituents or to ring junctions. We have taken advantage of this selectivity to prepare novel pyrene-2,6-bis(boronate) and perylene-2,5,8,11-tetra(boronate) esters amongst other polycyclic aryl boronates.[8] During the course of our studies on the system developed by Ishiyama et al. (L2=4,4-tBu2-2,2-bipyridine (dtbpy; 1 A)), we were intrigued that GC-MS analysis of the borylation reaction mixtures in situ did not show any borylation of the ligand 1 A, although 1 A could be detected by itself. We envisaged three possible reasons for this: 1) 1 A is firmly attached to the Ir center through the nitrogen atoms at all times; 2) it is simply not a suitable substrate for the catalyst, even if it were to dissociate; or 3) we would be unable to detect borylated 1 A by using our GC-MS method. We noted that pyridine itself is a poor substrate for the borylation reaction,[9], [10] whereas pyrrole and quinoline are readily borylated;[11] however, 2,6-chloropyridine and 2,6-dimethylpyridine were effectively borylated at the 4-position,[5], [12] and 5-bromo-2-cyanopyridine was borylated at the 3- and 4-positions in a 2:1 ratio.[13]