Catalytic C–H Borylation:
From Beginnings to Present
May 6, 2014
Professor Milton R. Smith, III
Department of Chemistry, Michigan State University
East Lansing, Michigan 48824-1322, USA
Chemists have sought methods for functionalizing sp2-C–H bonds that complement electrophilic
aromatic substitutions and orthometalation reactions. Building from the first thermal, catalytic coupling
of a borane and a hydrocarbon,1 our research group,2 and others, have developed highly active iridium
catalysts that exhibit unique regioselectivities for arene substitution and remarkable chemoselectivity
for C–H functionalization. For example, sp2-C–X bonds (X = Cl, Br, and I) that are commonly cleaved
in reactions with late transition metal complexes are typically inert to the Ir catalysts. Consequently,
these substrates generally give C–H borylated products. Extensions to heterocyclic substrates and
development of one-pot, catalytic reactions where the boronate esters are further transformed make
C—H borylation particularly attractive to synthetic chemists.
The combination of theory and experiment have provided a working model for the mechanism of C–H
borylation.3 Previously unappreciated electronic effects of this reaction will be described.4
(1) Iverson, C. N.; Smith, M. R. III J. Am. Chem. Soc. 1999, 121, 7696-7697.
(2) Cho, J.-Y; Tse, M. K.; Holmes, D; Maleczka, R. E. Jr.; Smith, M. R. III Science 2002, 295, 305-308.
(3) Vanchura, B. A.; 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.
(4) Preshlock, S. M., Ghaffari, B., Maligres, P. E., Krska, S. W., Maleczka, R. E. and Smith, M. R. J. Am. Chem.
Soc. 2013, 135, 7572-7582.
Milton R. Smith, III
Department of Chemistry
Michigan State University
East Lansing, Michigan 48824-1322, USA
Phone: 00-1-517-355-9715 x166, Fax: 00-1-517-353-1793
E-mail: smithmil@msu.edu
Milton “Mitch” Smith received his B.S. degree in 1986 from Caltech, where he carried out research with
Professor Terrence. J. Collins. He earned his Ph.D. in developing chemistry of metal diazene complexes
in the research group of Professor Gregory L. Hillhouse at the University of Chicago. In 1990, Smith
was awarded a Miller Fellowship at the University of California, Berkeley, where he spent two years in
the laboratories of Professor Richard A. Anderson synthesizing and exploring the reactivity of early
transition metal oxo and imido complexes. In 1992, Smith began his independent career at Michigan
State University as an Assistant Professor in the Chemistry Department. There he built a research
program centered on the reactivity of transition metal complexes with organoboron reagents. He was
promoted to Associate Professor with tenure in 1997 and Full Professor in 2002. In 1999, Professor
Smith and his graduate student, Carl Iverson, reported a thermal, catalytic synthesis of an organoborane
from a borane and a hydrocarbon where the sole byproduct was hydrogen gas. Shortly thereafter he
began a collaboration with Professor Robert E. Maleczka, Jr., his colleague at Michigan State. From a
relatively inefficient reaction, Maleczka, Smith, and their research team developed highly efficient
iridium catalysts that functionalize C–H bonds in a wide variety of aromatic and heteroaromatic
compounds. In 2005 Maleczka and Smith founded what would become BoroPharm, Inc. in 2006 and is
bringing the technology forged through the Maleczka-Smith collaboration to chemists in academia and
industry. Professor Smith and his research team continue to hone their C–H functionalization chemistry,
and on another research front, are developing new degradable polymers for biological and medical
applications.
Awards:
Presidential Green Chemistry Challenge Award (2008)