PERSPECTIVES whose by-product after reaction is water. isolate, rotenone, is a potent anti-leukemic The future of hypervalent iodine is likely The products of the catalytic reaction drug candidate as well (14). In 2005, the to be as varied as the chemists working in described by Uyanik et al. create the frame- Merck Company reported the synthesis of this area. Elucidating the mechanism, includ- work for a number of natural products with a drug candidate with this same backbone ing the steps that lead to a chiral product, will varied biological effects. The benzofuran that modulates the levels of serum triglyc- allow for further improvements in selectivity. products can form the starting point for the rides and high-density lipoprotein in the Ideally, this catalyst system, like any catalyst synthesis of more complex pharmaceutical blood(15). A synthesis of this target with developed, will be tested on other substrates candidates. For example, tremetone has both this new method could be accomplished in and reactions involving iodine-containing ntifungal and insecticidal properties and is fewer steps than the 2005 method, produce catalysts. Iodine chemistry, with its versa- derived from a plant extract. A similar plant less waste, and reduce cost. tile reactivity, is an excellent area to discover new, more environmentally friendly, greener Guiding iodine catalysts to organocatalysts. The chemistry described by their targets. (A)In the reac- A RN-10- or R N+O=I-o Uyanik et al. is but a taste of what is to come. tion described by Uyanik et Catalyst ( just a pinch) al., hydrogen peroxide rea with the salt formed by a chi R.N"上 1. T. Katsuki, K B Sharpless, Am. Chem. Soc. 102, 5974 al ammonium cation(R, N Pre-catalyst (just a pinch) (1980) 2. M. Uyanik, H. Okamoto, T Yasui, K Ishihara, Science 328.1376(20 idized iodine. This hyperva lent(hypoiodite then reacts B 3. T. wirth, Angew. Chem. Int. Ed. 44 4. R. M. Moriarty, J. Org. Chem. 70, 2893(2005). with the ketophenol to gen 5. T Dohi ef al., Chem. Commun.(Camb. )2005, 2205 erate the chiral benzofuran skeleton, where x can be one 6. I. Dohi et al., Angew. Chem. Int. Ed. 44, 6193(2005). of 7. C.I. Herrerias, T Y. Zhang, C.-) Li, Tetrahedron Lett. 47 8. Y Yamamoto, H Togo, Synlett 2006, 798(2006). xcellent selectivity for one of the two products that differ in handedness (in this case 10. R. D. Richardson et al., Synlett 2007, 0538(2007). the favored product has the 11. T. Dohi et al., Angew Chem. Int. Ed. 47, 3787(2008). 12. M. Uyanik, T. Yasui, K Ishihara, Angew. Chem. Int. Ed. COX group behind the plane 92175(2010) formed by the rest of the mol- Org. Process Res. Dev. 12, 679(2008) ecule: the other enantiomer 14. M. Abou-Shoer, F. E. Boettner, C.). Chang, I.M. Cassady, has this group in front). The compound is a starting point for a host of pharmaceutical candidates. B)The structural formula of the chiral ammonium cation is shown on the left. The three-dimensional rendering of 15. G.Q. hi et al. J Med. Chem. 48, 5589(2005) the chiral ammonium salt on the right has the nitrogen atom in blue and carbon atoms in gray, hydrogen and fluorine atoms are omitted for clarity 10.1126/ science.1191408 ATMOSPHERIC SCIENCE Getting to the critical Nucleus in the atmosphere could greatly improve of aerosol formation climate models Renyi Zhang A tmospheric aerosols--microscopic ever, fully understand at the molecular level considered to be a two-step process: First, particles suspended in Earths atmo- how aerosols form, creating one of the largest nucleation forms a"critical nucleus " which sphere--are a major environmen- sources of uncertainty in atmospheric mod- then grows to a detectable size(6). Classi tal problem. They degrade visibility, nega- els and climate predictions (1). Recent find- cal nucleation theory reveals that when the tively affect human health, and directly and ings suggest a path to a better understanding critical nucleus forms, the free energy of the indirectly influence climate by absorbing of aerosol formation(2-4) nucleating system reaches a maximum"the and reflecting solar radiation and modifying Aerosols can be directly emitted into the nucleation barrier"-beyond which aero- cloud formation. Researchers do not. ho Itmosphere--for example by plants, com- sol growth becomes spontaneous. The rate bustion, or sea spray--or form through a at which nucleation occurs is related to the na e ion contro college of Environmental sciences chemical process known as nucleation, in chemical makeup of the critical nucleus and China.3College of Environmentar' ty, Beijing, 100871. which gaseous molecules bond. Nucleation the gaseous concentrations of the nucleating ence and Engineer- produces a large fraction of atmospheric species(?). That rate is an important variable ing, Fudan University, Shanghai, 200433, China. Depart- aerosols, and investigators have frequently in simulations of aerosol formation in atmo- bserved nucleation in various environments, spheric models ( 8) University, College Station, TX 77843, USA. E-mail: renyi- luding urban, forested, and marine areas Previous studies, however, have not been zhang@tamu. edu (5). New particle formation is commonly able to directly measure nucleation rates 1366 11JunE2010Vol328scIencEwww.sciencemag.org1366 11 JUNE 2010 VOL 328 SCIENCE www.sciencemag.org PERSPECTIVES Getting to the Critical Nucleus of Aerosol Formation ATMOSPHERIC SCIENCE Renyi Zhang 1 ,2, 3 A better understanding of how aerosols form in the atmosphere could greatly improve climate models. Atmospheric aerosols—microscopic particles suspended in Earth’s atmo￾sphere—are a major environmen￾tal problem. They degrade visibility, nega￾tively affect human health, and directly and indirectly influence climate by absorbing and refl ecting solar radiation and modifying cloud formation. Researchers do not, how￾ever, fully understand at the molecular level how aerosols form, creating one of the largest sources of uncertainty in atmospheric mod￾els and climate predictions ( 1). Recent fi nd￾ings suggest a path to a better understanding of aerosol formation ( 2– 4). Aerosols can be directly emitted into the atmosphere—for example by plants, com￾bustion, or sea spray—or form through a chemical process known as nucleation, in which gaseous molecules bond. Nucleation produces a large fraction of atmospheric aerosols, and investigators have frequently observed nucleation in various environments, including urban, forested, and marine areas ( 5). New particle formation is commonly considered to be a two-step process: First, nucleation forms a “critical nucleus,” which then grows to a detectable size ( 6). Classi￾cal nucleation theory reveals that when the critical nucleus forms, the free energy of the nucleating system reaches a maximum—“the nucleation barrier”—beyond which aero￾sol growth becomes spontaneous. The rate at which nucleation occurs is related to the chemical makeup of the critical nucleus and the gaseous concentrations of the nucleating species ( 7). That rate is an important variable in simulations of aerosol formation in atmo￾spheric models ( 8). Previous studies, however, have not been able to directly measure nucleation rates 1State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China. 2College of Environmental Science and Engineer￾ing, Fudan University, Shanghai, 200433, China. 3Depart￾ments of Atmospheric Sciences and Chemistry, Center for Atmospheric Chemistry and the Environment, Texas A&M University, College Station, TX 77843, USA. E-mail: renyi￾zhang@tamu.edu whose by-product after reaction is water. The products of the catalytic reaction described by Uyanik et al. create the frame￾work for a number of natural products with varied biological effects. The benzofuran products can form the starting point for the synthesis of more complex pharmaceutical candidates. For example, tremetone has both antifungal and insecticidal properties and is derived from a plant extract. A similar plant isolate, rotenone, is a potent anti-leukemic drug candidate as well ( 14). In 2005, the Merck Company reported the synthesis of a drug candidate with this same backbone that modulates the levels of serum triglyc￾erides and high-density lipoprotein in the blood ( 15). A synthesis of this target with this new method could be accomplished in fewer steps than the 2005 method, produce less waste, and reduce cost. The future of hypervalent iodine is likely to be as varied as the chemists working in this area. Elucidating the mechanism, includ￾ing the steps that lead to a chiral product, will allow for further improvements in selectivity. Ideally, this catalyst system, like any catalyst developed, will be tested on other substrates and reactions involving iodine-containing catalysts. Iodine chemistry, with its versa￾tile reactivity, is an excellent area to discover new, more environmentally friendly, greener organocatalysts. The chemistry described by Uyanik et al. is but a taste of what is to come. References 1. T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 102, 5974 (1980). 2. M. Uyanik, H. Okamoto, T. Yasui, K. Ishihara, Science 328, 1376 (2010). 3. T. Wirth, Angew. Chem. Int. Ed. 44, 3656 (2005). 4. R. M. Moriarty, J. Org. Chem. 70, 2893 (2005). 5. T. Dohi et al., Chem. Commun. (Camb.) 2005, 2205 (2005). 6. T. Dohi et al., Angew. Chem. Int. Ed. 44, 6193 (2005). 7. C. I. Herrerías, T. Y. Zhang, C.-J. Li, Tetrahedron Lett. 47, 13 (2006). 8. Y. Yamamoto, H. Togo, Synlett 2006, 798 (2006). 9. R. D. Richardson, T. Wirth, Angew. Chem. Int. Ed. 45, 4402 (2006). 10. R. D. Richardson et al., Synlett 2007, 0538 (2007). 11. T. Dohi et al., Angew Chem. Int. Ed. 47, 3787 (2008). 12. M. Uyanik, T. Yasui, K. Ishihara, Angew. Chem. Int. Ed. 49, 2175 (2010). 13. K. Maruoka, Org. Process Res. Dev. 12, 679 (2008). 14. M. Abou-Shoer, F. E. Boettner, C.-J. Chang, J. M. Cassady, Phytochemistry 27, 2795 (1988). 15. G. Q. Shi et al., J. Med. Chem. 48, 5589 (2005). 10.1126/science.1191408 Guiding iodine catalysts to their targets. (A) In the reac￾tion described by Uyanik et al., hydrogen peroxide reacts with the salt formed by a chi￾ral ammonium cation (R4 N + ) and iodide, making water and oxidized iodine. This hyperva￾lent (hypo)iodite then reacts with the ketophenol to gen￾erate the chiral benzofuran skeleton, where X can be one of many different functional groups. The reaction shows excellent selectivity for one of the two products that differ in handedness (in this case, the favored product has the COX group behind the plane formed by the rest of the mol￾ecule; the other enantiomer has this group in front). The compound is a starting point for a host of pharmaceutical candidates. (B) The structural formula of the chiral ammonium cation is shown on the left. The three-dimensional rendering of the chiral ammonium salt on the right has the nitrogen atom in blue and carbon atoms in gray; hydrogen and fl uorine atoms are omitted for clarity. A B R4 N + IO– or R4 N + O=I–O– R4 N + I– H2 O2 H2 O X O O O X OH Pre-catalyst (just a pinch) Catalyst (just a pinch) N F 3 C F 3 C CF3 CF3 Published byAAAS on June 11, 2010 www.sciencemag.org Downloaded from