C&EN: CHEMISTRY HIGHLIGHTS 2002

STU BORMAN, C&EN WASHINGTON

Fujio Mizukami at the National Institute of Advanced Industrial Science & Technology, Tsukuba, Japan, and coworkers started out this year in organic chemistry by reporting a one-step catalytic process to convert benzene to the commodity chemical phenol [Science, 295, 105 (2002); C&EN, Jan. 7, page 23]. The technique is higher yielding than current cumene- and nitrous oxide-based industrial routes to phenol.

A team led by Noriyuki Suzuki of RIKEN (the Institute of Physical & Chemical Research), in Japan, made the first isolable five-membered cyclic alkyne (Image 1) [Science, 295, 660 (2002); C&EN, Jan. 28, page 52]. Cyclic alkynes are highly strained and tend to be unstable.

Iridium catalysts that enable the synthesis of arylboronates from hydrocarbons in one step--in contrast to traditional multistep routes--were developed by Milton R. Smith III, Robert E. Maleczka Jr., and coworkers at Michigan State University, and independently by a group led by John F. Hartwig of Yale University and Norio Miyaura and Tatsuo Ishiyama of Hokkaido University, Sapporo, Japan [Science, 295, 305 (2002); J. Am. Chem. Soc., 124, 390 (2002); C&EN, Feb. 4, page 26].

The first chiral olefin metathesis catalyst that's polymer-supported and recyclable was developed by Richard R. Schrock at MIT, Amir H. Hoveyda at Boston College, and coworkers [Angew. Chem. Int. Ed., 41, 589 (2002); C&EN, Feb. 18, page 13]. Advantages of the molybdenum-based catalyst include easy reaction cleanup, high enantioselectivity, and reusability.

Karl Anker Jørgensen and coworkers at Aarhus University, Denmark, and Benjamin List of Scripps Research Institute discovered the same proline-catalyzed technique for the direct asymmetric a-amination of unmodified aldehydes, using azodicarboxylate reagents (Image 2) [Angew. Chem. Int. Ed., 41, 1790 (2002); J. Am. Chem. Soc., 124, 5656 (2002); C&EN, June 3, page 47]. Jørgensen's group also developed a ketone version of the reaction [J. Am. Chem. Soc., 124, 6254 (2002)]. The reactions could lead to one-pot industrial syntheses of enantiomerically pure amino acids.

A "green" synthetic route to fluorobenzene and other fluorinated aromatics that gives water as the only by-product was discovered by Mas A. Subramanian and Leo E. Manzer of DuPont [Science, 297, 1665 (2002); C&EN, Sept. 9, page 35].

Several groups working independently determined the source of acrylamide--a neurotoxin and cancer agent discovered to be present in potato chips, french fries, and other cooked foods. It's the Maillard reaction, in which the amino acid asparagine reacts with a reducing sugar to produce acrylamide during high-temperature cooking [Nature, 419, 448 and 449 (2002); C&EN, Oct. 7, page 7].

Last year, Patrick G. Harran and coworkers at the University of Texas Southwestern Medical Center at Dallas synthesized a structure proposed in 1991 for diazonamide A, an anticancer natural product [Angew. Chem. Int. Ed., 40, 4765 and 4770 (2001); C&EN, Dec. 17, 2001, page 11]. They found the proposed structure to be wrong, but the synthesized compound turned out to have anticancer properties as powerful as those of the natural product. This year, a group led by K. C. Nicolaou of Scripps and the University of California (UC), San Diego, reported a total synthesis of the correct natural-product structure (Image 3) [Angew. Chem. Int. Ed., 41, 3495 (2002); C&EN, Sept. 23, page 19].

The first total synthesis of ramoplanin--an antibiotic two to 10 times more active against some gram-positive bacteria than vancomycin, the antibiotic of last resort--was achieved by Scripps's Dale L. Boger and coworkers (Image 6) [J. Am. Chem. Soc., 124, 5288 (2002); C&EN, May 13, page 8].

Steven V. Ley's group at the University of Cambridge carried out the first total synthesis of the bioactive alkaloid (+)-plicamine (Image 4) [Angew. Chem. Int. Ed., 41, 2194 (2002); C&EN, June 17, page 26]. All transformations used in the synthesis were done with supported reagents and scavengers, avoiding the need for any chromatographic, crystallization, or distillation steps.

Jeffrey D. Winkler and coworkers at the University of Pennsylvania reported the first total synthesis of the natural product ingenol (Image 5), a long-standing synthetic target [J. Am. Chem. Soc., 124, 9726 (2002); C&EN, Aug. 19, page 11]. They established the correct stereochemistry of ingenol's unusual trans intrabridgehead by using dioxenone photochemistry developed by their group.

The first "heterosuperbenzene" (Image 7), a graphitelike structure with 13 fused benzenoid rings, was synthesized by Sylvia M. Draper and coworkers at the University of Dublin, Trinity College [J. Am. Chem. Soc., 124, 3486 (2002); C&EN, April 8, page 22].

And on the energy front, the nonpolluting fuel hydrogen (H₂) is currently made by steam reforming of fossil fuels, but James A. Dumesic and coworkers at the University of Wisconsin, Madison, developed a platinum-catalyzed process that produces it from biomass [Nature, 418, 964 (2002); C&EN, Sept. 2, page 29].