Celebrating Professor Barry M. Trost's 80th Birthday

Abstract

For more than a half of a century, Barry Trost has been a highly influential scientist in almost every aspect of organic synthesis, including methodology and total synthesis. He started his career at a remarkably young age. After obtaining his B.Sc. degree in chemistry from the University of Pennsylvania (1962), he moved to MIT where he completed his Ph.D. with H. O. House, working on fundamental aspects of enolate chemistry. Remarkably, at the age of 24, immediately after obtaining his Ph.D. degree in 1965, he accepted an offer of an Assistant Professorship at the University of Wisconsin. Four years later, at the age of 28, he became a Full Professor. In 1987, he moved to Stanford University, where he was appointed Tamaki Professor of Humanities and Sciences. Trost's remarkable impact on multiple areas of organic chemistry is documented in nearly 1000 research publications and patents. He is one of the world‘s leading organic chemists, a member of the National Academy of Sciences, and one of the most cited chemists worldwide. The scientific community has recognized him with numerous awards, including the Paul Janssen Prize, ASSU Graduate Teaching Award, Bing Teaching Award, ACS Roger Adams Award, Presidential Green Chemistry Challenge Award, Herbert C. Brown Award for Creative Research in Synthetic Methods, Belgian Organic Synthesis Symposium Elsevier Award, Nichols Medal, Yamada Prize, ACS Nobel Laureate Signature Award for Graduate Education in Chemistry, ACS Cope Award, Israel Chemical Society Barry Cohen Medicinal Chemistry Award, the Ryoji Noyori Prize, the August-Wilhelm-von-Hofmann Medal, the International Precious Metal Institute Junichiro Tanaka Distinguished Achievement Award, the Linus Pauling Medal Award, to name a few. The nearly 600 former Trost group members, graduate students, and postdocs from all around the world, who take leadership positions in academia and industry, have amplified Barry Trost's extraordinary impact on science and organic synthesis in particular. We are proud of being members of the Trost family. Keinan belonged to the University of Wisconsin era (Figure 1) and was working on Pd-catalyzed allylation reactions (1977–79), while Portnoy worked at Stanford on Ru-catalyzed enone-alkyne coupling reactions (1995–97). The Israeli aspect of Trost's group includes two additional postdocs, Genia Sklute and Elliad R. Silcoff. In 1997 Trost became Doctor Scientiarum Honoris Causa of the Technion-Israel Institute of Technology. Barry M. Trost and Ehud Keinan, in 1978, operating a flow system loaded with phosphinated polystyrene beads and a Pd(0) catalyst that carries out efficient allylic alkylation (JACS, 1978, 100, 7779–7781). Photo by Duane Hopp, adopted from Michael Wilpers, UIR Newsletter, 1978, 12 (1), 25. This special issue, titled “Organometallic Door to Synthesis,” highlights Trost's recognition of the enormous potential of transition metals in organic synthesis at a time when the two fields were very much separated. His high-impact program on palladium catalysis includes several pioneering milestones. His allylic alkylations demonstrated high chemo-, regio- and enantioselectivity. His palladium-catalyzed trimethylenemethane chemistry enabled many cycloaddition reactions that complement the Diels–Alder reaction. His palladium-hydride intermediates led to novel ene/yne-cyclization reactions to produce 1,4- or 1,3-dienes, allowing for synthesizing macrocyclic and medium-ring systems. Trost's ruthenium-catalyzed organic synthesis demonstrated the first examples of catalytic processes involving vinylidene and allenylidene ruthenium intermediates. This chemistry enabled unprecedented reactions and products, such as 1,5-dicarbonyl compounds, [2+2+2] cycloaddition of alkynes to 1,5-cyclooctadiene, and a [5+2] cycloaddition to form seven-membered rings. Application of new binuclear chiral zinc-catalysts allowed for asymmetric transformations, such as the aldol, Mannich, and Michael reactions, as well as the asymmetric alkinylation of carbonyls. Trost's new tools of transition metal catalysis and main group element reagents have enabled the total synthesis of more than 200 molecular targets, many of which are biologically active. Most of the manuscripts contributed to this Special Issue by Trost group alumni deal with metal-catalyzed synthesis. However, other contributions involve metal-free synthetic methodology, as well as total synthesis. Bellow we provide brief summaries of these contributed articles. F. Dean Toste and Christopher A. Kalnmals provide an extensive review of many synthetic methods less known than the celebrated allylic alkylations, metal-catalyzed cycloisomerizations, and trimethylenemethane cycloadditions. Yet, these highly useful methods have enjoyed widespread adoption by the community of organic synthesis. These “less famous” synthetic methods, which include metal-catalyzed alkyne-alkyne and alkyne-alkene couplings, as well as reduction/oxidation reactions, were used for the total synthesis of a variety of natural products, pharmaceuticals, and other complex bioactive molecules. Adrien Quintard presents interesting multi-catalytic combinations of iron/copper metal- and organo-catalysis (mostly developed by his group) for overcoming the limitations of single-catalyst reaction mode. He screens different categories of such reactions and outlines the advantages with a particular emphasis on enantioselective catalysis. Zachary T. Ball reviews the use of boronic acid reagents in bioconjugation. These reagents, combined with metal catalysts, offer unique selectivity patterns in modifying biopolymers. As a result, they provide access to novel biopolymer architectures for various uses in chemical biology. Virginie Ratovelomanana-Vidal and Jean-Pierre Genet review the development of atropisomeric ligands and chiral transition metal complexes for asymmetric hydrogenation reactions. These transformations, which include reduction of alkenes, ketones, and heteroaromatics, were applied in industrial processes and total synthesis of biological targets. Michael J. Krische describes in his communication two distinct catalytic methods of reductive biaryl cross-coupling. He employs these formate-mediated transformations for the coupling of pyridines and anisoles. Phil Ho Lee describes a new method for preparing highly functionalized benzothiazines from readily available starting materials. The methodology uses Rh- and Ir-based catalytic systems that benefit from broad scope, high functional group tolerance, and good regioselectivity. Joshua D. Sieber describes the exploration of a variant of Pd-catalyzed allylic alkylation, which employs allenamides as allyl electrophile-forming substrates. This regioselective reaction represents an addition of a carbon nucleophile to the terminal double bond of an allenic system, a complementary method to the more common Pd-catalyzed allylic substitution. Oliver R. Thiel surveys the application of the green methodology in the development of processes leading to active pharmaceutical ingredients. He demonstrates how concepts such as atom economy, solvent minimization, reagent optimization, synthetic convergence, reduced energy use, real-time analysis, and strong safety focus have contributed to more environmentally benign processes. Alison J. Frontier reviews methods for concurrent installation of multiple quaternary stereogenic centers in cyclic and polycyclic molecules, focusing on the cyclization steps. The review covers processes disclosed in the total synthesis of natural products and methodology studies during the past two decades. Christian G. Bochet surveys the application of the photochemical methodology, which independently targets different photosensitive sites using light beams of different wavelengths. The review follows the extension of this synthetic methodology to various fields, including catalysis, chemical biology, and lithography. John D. Chisholm describes a metal-free method for amino-oxidation of electron-rich olefins, utilizing anilines in combination with an inexpensive organic oxoammonium salt as a key reagent. He demonstrates that the solvent controls the stereochemical outcome of this addition to the olefin substrate. Debayan Sarkar describes in his communication the oxidative cleavage of a hydroxybenzyl substituent of various naphthols with a concomitant dearomatization and introduction of bromo- and azido-functionalities onto the cyclic scaffold. Guillaume Mata and Christopher A. Kalnmals shed light on the total synthesis of numerous natural products, pharmaceuticals, and other biorelevant molecules, performed in the Trost laboratories during the past 20 years. Among more than a hundred compounds, prepared by Trost and coworkers during this period, many complex targets, such as bryostatins 3 and 16, callipeltoside A, ushikulide A, codeine, perophoramidine, and lasonolide A, are highlighted in this survey. Georges Massiot shares in his essay insights from the field of natural products and the work of Prof. Trost in this research area. He includes a description of the cases from his own experience and outlines the difficulties and remaining problems in this field. Uli Kazmaier focuses on the bottromycin class of natural products, emphasizing the synthetic approaches to bottromycin and its analogs, spanning half a century of research. George A. O'Doherty describes the synthesis of a model compound of a proposed biosynthetic precursor of Gilvocarcin M and its regioisomeric analog, to elucidate the biosynthetic origin of this natural product. In both model molecules, a carbasugar unit mimics the original sugar portion of the natural product, while O-glycoside linkage replaces the C-glycoside connection. Paul R. Hanson describes an iterative one-pot sequential synthetic route to the demethylated macrolactone fragment of (−)-lyngbouilloside, en route to the preparation of the complete unnatural analog of this natural product. Seijiro Matsubara reveals in his paper that as little as three substituents are sufficient to convert cubane into a chiral molecule, which can serve as a chiral pharmacophore or a chiral ligand. The routes to various trisubstituted cubanes involve metal reagents and HPLC enantiomeric resolution. Barry Trost has always been a highly gifted scientist blessed with imagination, creativity, scholarship, dedication, and enthusiasm for chemistry. He has served as a role model for many generations of young scientists, and even at the age of 80, he keeps producing excellent science. We celebrate his 80th birthday and wish him all the best for many years to come. We wish to thank all those who took part in this endeavor, particularly the authors who shared with us their thoughts and perspectives, the reviewers and the highly professional team at Wiley-VCH. Enjoy your reading!