2731 © Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2731–2738 K. V. N. Esguerra, J.-P. Lumb Synpacts Syn lett Adapting Melanogenesis to a Regioselective C–H Functionaliza- tion of Phenols Kenneth Virgel N. Esguerra Jean-Philip Lumb* Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, H3A 0B8, Canada jean-philip.lumb@mcgill.ca Received: 10.06.2015 Accepted: 04.08.2015 Published online: 16.09.2015 DOI: 10.1055/s-0034-1381059; Art ID: st-2015-p0435-sp Abstract The importance of aromatic carbon–heteroatom bonds to the function of natural products, electronic materials, and pharmaceu- tically active compounds motivates considerable effort to improve the efficiency of constructing these bonds. Melanogenesis, which is a ubiq- uitous process by which organisms produce pigments, generates func- tional materials with high heteroatom content from simple phenolic precursors at the sole expense of reducing molecular oxygen to water. This article outlines our efforts towards the development of a tyrosinase mimic for the aerobic oxygenation of phenols that were inspired by melanogenesis, and highlights its potential to functionalize multiple ar- omatic C–H bonds in a single operation. Key words biomimetic catalysis, aerobic oxidation, phenols, dearo- matization, enzymes, C–H functionalization, copper Catalytic aerobic oxidation reactions, which derive the energy for bond formation from the reduction of molecular oxygen (O 2 ), offer attractive opportunities for the function- alization of C–H bonds with high degrees of efficiency. 1 Ar- omatic C–N and C–O bonds are omnipresent in specialty chemicals, which are, in turn, centrally important to phar- maceutical and materials sciences. Because the overwhelm- ing majority of these specialty chemicals are produced from starting materials of low heteroatom content, the oxidation of aromatic C–H bonds is fundamentally important to their synthesis, 2 and significant efforts have been made to im- prove the efficiency of heteroatom bond-forming steps [Scheme 1(a)]. 3 Our group has approached this challenge by studying chemical transformations that occur in nature, 4 with the goal of adapting these processes to laboratory synthesis. In the context of functionalizing aromatic C–H bonds, we were drawn to the biosynthesis of melanin pigments (mela- nogenesis), which is a complex oxidative polymerization of phenols that gives rise to browning of fruit, 5 the pigmenta- tion of skin, 6 and the sclerotization of insect cuticles. 7 Mela- nogenesis is characterized by the functionalization of two C–H bonds in L-tyrosine to form aromatic C–N or C–O bonds. 8 The process is regioselective and exceptionally effi- cient, especially when one considers the challenges of forming aromatic C–N or C–O bonds by conventional C–H oxidation (Scheme 1, a). 9 Mechanistically, melanogenesis is distinct from conventional cross-coupling reactions, 10 which typically form the heteroatom–carbon bond by re- ductive elimination of a transition metal. This can be the Kenneth Virgel N. Esguerra (left) obtained a B.Sc. in biology at the University of Toronto, St. George, and a M.Sc. in molecular imaging, studying with Dr. Leonard G. Luyt at the University of Western Ontario. He then began his Ph.D. studies in organic chemistry in 2011 at McGill University under the supervision of Dr. Jean-Philip Lumb. Dr. Jean-Philip Lumb (right) obtained his B.A. from Cornell University in 2002, graduating Magna Cum Laude with degrees in Chemistry and French Literature. In 2003, he moved to the University of California, Berkeley, where he was an ACS Organic Division Fellow in the research group of Professor Dirk Trauner. From 2008 to 2011 he was a Ruth L. Kirschstein Postdoctoral Fellow at Stanford University, working under the supervision of Prof. Barry M. Trost. In 2011, Dr. Lumb began his in- dependent career at McGill University. SYNLETT0936-52141437-2096 © Georg Thieme Verlag Stuttgart · New York 2015, 26, 2731–2738 synpacts Heruntergeladen von: New Mexico State University. Urheberrechtlich geschützt.