| The Ir-catalyzed aromatic C-H borylation discovered by our group has been demonstrated as a powerful tool for direct functionalization of unactivated arenes. This reaction provides a method for preparation of aryl boronic esters directly from arenes and bypasses the need for aryl halides precursor. It also comes with a unique sterics-directed regioselectivity, thus is complementary to traditional chemistry and able to provide aromatic building blocks with substitution patterns difficult to access via other routes. The cleanliness of this reaction allows succeeding reactions performed without isolation and purification of the boronic ester intermediates.;Through the years, we have successfully demonstrated the utility of this C-H borylation by combining it with subsequent chemical events in the one-pot fashion. By doing this, we are able to not only elaborate this reaction into synthetically useful protocols toward the preparations of many functionalized aromatic motifs, but also discover new chemistries. Along these lines, we have been working on both transformating the boryl group to other functionalities and carrying on aromatic substitution with the boronic ester groups intact. We have established the borylation/oxidation protocol for the preparation of substituted phenols, the borylation/deuteration protocol for the preparation of specifically deuterated aromatics, and the borylation/amidation/oxidation protocol for the preparation of 5-substituted 3-amidophenols. At the same time, we have also demonstrated the viability to extend the Ir-catalyzed aromatic C-H borylation chemistry from simple arenes to aromatic amino acid substrates and successfully carried out the borylation/oxidation protocol to prepare hydroxylated phenylalanine and tryptophan derivatives and analogues. Moreover, we have discovered that the proto-/deuterio-deborylation reaction of aryl boronic acids/esters is an Ir-catalyzed reaction and therefore established a thermal, acid/base-free deborylation condition on its own. The borylation/amidation/oxidation protocol comes with an undesired Suzuki side-reaction, and we are able to exploit it not only by utilizing its potential useful products, but also by giving preliminary success for a possible borylation/amidation/Suzuki protocol that uses the same Pd catalyst and ligand to promote both the amidation and the Suzuki reactions.;We are also applying the C-H borylation chemistry strategically to total synthesis of natural product autolytimycin. We have been able to demonstrate that autolytimycin, a new ansamycin superfamily member exhibiting antitumor, anti-inflammation, and antiviral activities, can potentially be assembled using our borylation/amidation/oxidation protocol with advanced intermediates. We have prepared the individual segments, and successfully demonstrated that the borylation/amidation/oxidation process can be successfully applied to the total synthesis in the relatively late stage. The completion of the total synthesis can be expected in the near future. |
