methodology & mechanism
Please click on the links above for a more detailed research description
Like organotins and organosilanes, organoboranes perform beautifully in Pd-mediated cross-coupling reactions also know as Suzuki couplings. Indeed, the Suzuki cross-coupling is the third most common C–C bond forming reaction used for the preparation of drug candidates.
Several years ago, we began a collaboration with Professor Milton R. “Mitch” Smith, III to explore catalytic aromatic C-H activation-borylation as a new approach to novel and highly useful aromatic building blocks for organic synthesis. In 1999, Professor Smith and his co-workers first reported on Ir-based catalysts that were remarkably selective for the C-H activation-borylation of unactivated arenes.
The mildness of these catalysts and reaction conditions under which they operate allow the borylation of arenes containing a variety of functional groups. Moreover the regiochemical outcomes of these reactions often complement those observed in traditional aromatic substitutions. Owing to these features, catalytic aromatic C-H activation-borylation represents a new and attractive approach to aromatic and heteroaromatic boronic esters. Furthermore, we have designed reaction sequences that merge C-H activation-borylation reactions with cross-couplings, C-N bond forming reactions, oxidations, reductions, deuterium/boron exchange reactions, etc. These processes allow unique access to functionalized aromatic building blocks that are novel or only accessible by protracted, costly, and otherwise unattractive routes.
An example of our one-pot C-H activation/borylation/oxidation based preparation of phenols is shown below.
Selected organoborane related publications:
“Practical One-Pot C–H
Activation/Borylation/Oxidation: Preparation of 3-Bromo-5-Methylphenol
on a Multi-Gram Scale” Norberg, A. M.; Smith, M. R., III; Maleczka, R.
E., Jr. Synthesis 2011, 857–859.
“Electronic Effects in Iridium C–H Borylations:
Insights From Unencumbered Substrates and Variation of Boryl Ligand
Substituents” Vanchura, B. A., II; Preshlock, S. M.; Roosen, P. C.
Kallepalli, V. A.; Staples, R. J.; Maleczka, R. E., Jr.; Singleton, D.
A.; Smith, M. R., III Chem. Commun.
2010, 46, 7724–7726.
“Divergent Synthesis of 2,3,5-Substituted Thiophenes
by C–H Activation/Borylation/Suzuki Coupling" Kallepalli, V. A.;
Sanchez, L.; Li, H.; Gesmundo, N. J.; Turton, C. L.; Maleczka, R. E.,
Jr.; Smith, M. R., III Heterocycles
2010, 80, 1429–1448.
“Boc Groups as Protectors and Directors for
Ir-Catalyzed C–H Borylation of Heterocycles” Kallepalli, V. A.; Shi,
F.; Paul, S.; Onyeozili, E. N.; Maleczka, R. E., Jr.; Smith, M. R., III
J. Org. Chem. 2009, 74, 9199–9201.
“Getting the Sterics Just Right: A Five-Coordinate
Iridium Trisboryl Complex that Reacts with C—H Bonds at Room
Temperature” Chotana, G. A.; Vanchura, B. A., II; Tse, M. K.; Staples,
R. J.; Maleczka, R. E., Jr.; Smith, M. R., III Chem. Commun. 2009, 5731–5733.
“Iridium-Catalyzed Borylation of Thiophenes:
Versatile, Synthetic Elaboration Founded on Selective C–H
Functionalization” Chotana, G. A.; Kallepalli, V. A.; Maleczka, R. E.,
Jr.; Smith, M. R., III Tetrahedron
2008, 64, 6103–6114.
“Ir-Catalyzed Functionalization of 2-Substituted Indoles at the 7-Position: Nitrogen-Directed Aromatic Borylation” Paul, S.; Chotana, G. A.; Holmes, D.; Reichle, R. C.; Maleczka, R. E., Jr.; Smith, M. R., III J. Am. Chem. Soc. 2006, 128, 15552–15553.
“Aromatic Borylation/Amidation/Oxidation: A Rapid Route to 5-Substituted-3-amidophenols” Shi, F.; Smith, M. R., III; Maleczka, R. E., Jr. Org. Lett. 2006, 8, 1411–1414.
“One-Pot Borylation/Amination Reactions: Synthesis of Arylamine Boronate Esters from Halogenated Arenes” Holmes, D.; Chotana, G. A.; Maleczka, R. E., Jr.; Smith, M. R., III Org. Lett. 2006, 8, 1407–1410.
“C–H Activation/Borylation/Oxidation: A One-Pot Unified Route To Meta-Substituted Phenols Bearing Ortho/Para-Directing Groups” Maleczka, R. E., Jr.; Shi, F.; Holmes, D.; Smith, M. R., III J. Am. Chem. Soc. 2003, 125, 7792–7793.
“Remarkably Selective Iridium Catalysts for the Elaboration of Aromatic C–H Bonds” Cho, J.-Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E., Jr.; Smith, M. R., III Science 2002, 295, 305–308.