SCIENCE & TECHNOLOGY bomethoxy-3-cyano-2,3-diphenylpropane from (21£,4S)-2-carbomethoxy-4-cyano2,4-diphenyl-3-butanone [Org. Lett., 5, 2531 (2003)]. Reducing the cyano group in the product to an amine would yield optically pure 7-amino acids, which can be used to make heterocycles, peptides, and other specialty chemicals, he pointed out. Now, Garcia-Garibay and graduate students Danny Ng and Zhe Yang have used MONG THE MOST CHALLENGup to 95% and enantiomeric excesses ap- the reaction as a key step in the total syning structural motifs in syn- proaching 100%. thesis of three natural products: a-cuthetic organic chemistry are The idea is simple: Take a crystalline parenone, herbertenolide, and tochuinyl adjacent quaternary centers. chiral acetone derivative acetate. In all cases, the Miguel A. Garcia-Garibay, a with six different subchallenge was to prepare an chemistry professor at the University of stituents and photochemappropriate carefully deCalifornia, Los Angeles, believes that car- ically break the two bonds signed ketone precursor for bon-carbon bond formation through to the carbonyl group. photochemical solid-state photochemical decarbonylation of a When CO is removed, the decarbonylation. Once the crystalline ketone is a viable alternative resulting radicals then join precursor was in place, way to create this motif, especially for to form a bond that mainthe reactions proceeded compounds of high value. Last month, tains the absolute configusmoothly Garcia-Garibay described applications ration of the substrate. "In The strategy will not of the reaction to total synthesis of com- general, radicals are not work for every ketone, plex molecules at the ACS national meet- chiral," Garcia-Garibay exGarcia-Garibay said. In ing in New York City. plained. "But being in the fact, the requirements of Natural products with vicinal quater- chiral environment of the the reaction can seem nary chiral centers are very difficult to crystal, they will be con- Garcia-Garibay overwhelming at first ~~~ prepare by solution chemistry, Garcia- figurationally trapped. And ~~ glance: The ketone has to Garibay said. On the other hand, if an because the two electrons are very close be a crystal that allows the passage of appropriate substrate for photochemi- to each other, they quickly form the de- light, and the bonds around the carbonyl cal decarbonylation can be prepared, the sired bond." must be severable by the irradiation. solid-state reaction is straightforward, In this way, Garcia-Garibay and co- These requirements can be met by informing the desired product in yields of workers have prepared (2R,3R)-2-car- troducing radical-stabilizing groups. Furthermore, the product must be crystalline and must be able to coexist with the substrate in the same crystal lattice ALTERNATIVE CHEMISTRY or else the crystal will melt or turn into Photodecarbonylation of ketone crystals preserves absolute configuration amorphous glass. These requirements mean that the structural similarity of substrate and product must be high. C09H FROM
THE ACS
MEETING
C-C BOND FORMATION IN ORGANIC CRYSTALS
Solid-state photochemical reaction offers alternative route to vicinal quaternary centers
A
Tochuinyl acetate
"IT SEEMS TO BE a lot of trouble to get everything in place for this reaction to work," Garcia-Garibay said. "But every reaction has certain limitations; we just get used to them. Once we know the rules for this one, we can take advantage of what it can offer." The advantages include exquisite chemo- and stereospecificity, due to the constraints of the crystal environment, as well as zero use of solvent and little or no workup of the product, Garcia-Garibay pointed out. "For high-value chemicals, the reaction would be practical," Garcia-Garibay said. "Although the chemical engineering would be very different, it could be competitive for compounds for which the transformation cannot be achieved more easily by conventional m e a n s . — A . MAUREEN ROUHI
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