PCA ETR EDITORIAL FEATURE SPECIAL

Asymmetric Catalysis

ighlighting this issue of William Knowles and his colleagues at but for the most part, these serve to re- PNAS and the forthcoming Monsanto demonstrated that rhodium mind us how much still remains to be one* is a Special Feature complexes containing chiral phosphine done to advance our understanding to comprising 8 Perspectives ligands were able to catalyze the enan- the point where rational design of such H catalysts can be undertaken with some and 44 research articles that cover tioselective addition of H2 to one of the aspects of asymmetric catalysis, the faces of a prochiral olefinic substrate confidence. Finally, one Perspective phenomenon whereby a chiral catalyst generating a chiral COH center with draws on insights derived from studies promotes the conversion of an achiral high enantioselectivity. This process was on asymmetric catalysis to speculate substrate to a chiral product with a pref- soon commercialized to produce the about the origins of the symmetry- erence for the formation of one of the anti-Parkinson drug, L-dopa, followed breaking that gave rise to the enantio- mirror image isomers (enantiomers). over the next three decades by the de- meric enrichment that characterizes The demand for chiral compounds, velopment of many other commercial living systems. Although the develop- often as single enantiomers, has esca- processes, as well as laboratory scale ments to date may engender the notion lated sharply in recent years, driven syntheses, to generate enantiomerically that little remains to be done, quite the particularly by the demands of the phar- enriched compounds. In recognition of converse is true. The most formidable maceutical industry, but also by other his achievement, Knowles shared the challenges of this field still lie ahead. applications, including agricultural 2001 Nobel Prize in chemistry with Interfacing with a variety of disci- chemicals, flavors, fragrances, and mate- Ryoji Noyori, also for work on asym- plines, including organic synthesis, organometallic chemistry, kinetics and rials. Two-thirds of prescription drugs metric catalytic hydrogenation, and with mechanisms, structural chemistry, biol- are chiral, with the majority of new K. Barry Sharpless for his work on ogy, and materials science, the theme of chiral drugs being single enantiomers. asymmetric catalytic oxidation. asymmetric catalysis seems particularly Although the most obvious applications This collection of Special Feature ar- appropriate for highlighting in a multi- are bio-related, materials science also ticles serves as an eloquent testimonial disciplinary journal such as PNAS. relies on the properties imparted by to how far this field has evolved. While This Special Feature on asymmetric chirality, notably in chiral polymers several contributions deal with the O O catalysis is one of a series of such and liquid crystals. This widespread generation of chiral C H and C O collections of articles that PNAS has demand for chiral compounds has stim- centers through asymmetric catalytic published in recent years, comprising ulated intensive research to develop hydrogenation and oxidation, respec- Perspectives and research articles fo- improved methods for synthesizing such tively, themes that dominated the early cussed on specific cutting-edge multidis- compounds. years of the field, the scope of asymmet- ciplinary topics. Themes of previous Historically, enantiomerically enriched ric catalysis has grown to encompass a features have included: Astrobiology; compounds were generated either by wide range of other reactions, greatly Evolutionary Developmental Biology; chemical transformation of an enantio- expanding the accessible methodologies Rapid Climate Change; Social and merically enriched precursor, often de- for generating enantiomerically enriched Behavioral Sciences; Supramolecular rived directly or indirectly from nature’s organic compounds. More than half the Chemistry and Self-Assembly; Bio- chiral pool, or by resolving an equimolar articles in the collection deal with the inorganic Chemistry; and, most recently, (racemic) mixture of the two enanti- generation of chiral carbon centers Science and Technology for Sustainable omers. Both of these approaches suffer through COC bond forming reactions, Development. Scheduled for future is- from potentially severe drawbacks, the including the nucleophilic addition of sues of PNAS are special features on former in requiring stoichiometric organometallic reagents to aldehydes, Natural Products Synthesis and on amounts of a suitable precursor and the ketones, and imines; conjugate addi- Chemical Theory and Computations. latter in typically yielding only up to tions; aldol reactions; allylic alkylations; One objective of these Special Features 50% of the desired enantiomer. Diels–Alder reactions; 1.3-dipolar addi- is to advance the journal’s ongoing ini- Asymmetric catalysis, in which each tions; enyne cyclizations; cyclopropana- tiative to expand its coverage of the molecule of chiral catalyst, by virtue of tion; and olefin-metathesis; as well as physical and social sciences. PNAS con- being continually regenerated, can yield with the application of these and related tinues to encourage and welcome re- many molecules of chiral product, has reactions to the synthesis of chiral natu- search articles in all areas of the natural significant potential advantages over ral products. Other themes include: the and social sciences and mathematics. these older procedures. Indeed, enantio- design and application of new chiral li- Jack Halpern merically pure compounds are produced gands, including helical polymers and in nature by such chirality transfer from resin-supported phosphines, for metal- Barry M. Trost enzymic catalysts. However, it was only based asymmetric catalysts; enhancing relatively recently that such asymmetric the enantioselectivity of enzymes by *Supplementing the articles in this issue, the forthcoming catalysis, with enantiomeric excesses ap- ‘‘adaptive evolution’’; and modeling issue of PNAS (no. 16, April 20, 2004) will include 4 addi- proaching 100%, was achieved with syn- aspects of asymmetric catalysis compu- tional Perspectives and 22 additional research articles that thetic catalysts. A major breakthrough tationally. A few articles address mecha- also are part of this Special Feature. occurred in the early 1970s, when nistic aspects of asymmetric catalysis, © 2004 by The National Academy of Sciences of the USA

www.pnas.org͞cgi͞doi͞10.1073͞pnas.0401811101 PNAS ͉ April 13, 2004 ͉ vol. 101 ͉ no. 15 ͉ 5347 Downloaded by guest on October 2, 2021