Science/Technology This a c h i e v e m e n t of organic chemistry professor Eric N. Jacobsen is the latest advance in efforts to make chiral compounds from ole fins. It parallels the catalytic asym metric epoxidation of allylic alco hols and catalytic asymmetric dihydroxylation of unsubstituted olefins devised by organic chemistry pro fessor K. Barry Sharpless at Massa chusetts Institute of Technology. Like the chemistry of Sharpless, the new reaction creates two dis symmetric carbon atoms in one shot. As a catalytic reaction, it is superior to stoichiometric ones that consume a mole of reagent for every mole of product formed. And though the new reaction is not yet honed to perfection, it has the potential to give both high yields and high enantiomeric excesses. Benkovic: focus on catalysis Working with graduate student Lerner says the response to the Wei Zhang and undergraduate re initial paper in Science has been two search student Jennifer L. Loebach fold. One response is that many sci (to whom Eli Lilly & Co. provided entists have asked for permission to a summer research scholarship), Ja apply the technique to their own cobsen made catalysts as chelates work. The other response, Lerner of manganese(III) with imines of notes, is from "molecular biologists, (R,R)- or (S,S)-l,2-diamino-l,2-diphesaying, This is a fantastic idea, but nylethane and substituted salicylalwe know how to make it even bet d e h y d e s . Chemistry d e p a r t m e n t ter/ " This second response, he says, crystallographer Scott R. Wilson ver "is very comforting, because it ified structures of catalysts as their means that the community is behind bis(acetonato) derivatives. it and tinkering with it." That tink The Jacobsen epoxidation seems ering, Lerner believes, will un to work better with cis- than with doubtedly lead to improvements in trans-olefins. For example, trans-βthe technique. D methylstyrene gave a 93% yield but only 20% enantiomeric excess. By contrast, c/s-^-methylstyrene gave a 73% yield and 84% enantiomeric ex cess. Also, catalysts based on hindered salicylaldehydes seem to give high Chemists at the University of Illi er enantiomeric excesses. Catalyst nois, Urbana-Champaign, have de made from 3-£er£-butyl-2-hydroxyvised a cheap method for catalytic benzaldehyde was superior in this asymmetric epoxidation of unsubsti- respect to that made from salicylaltuted olefins [/. Am. Chem. Soc, 112, dehyde itself. The Illinois research 2800 (1990)]. The technique may be ers made the ferf-butyl compound applied to research syntheses of nat by formylation of cheap 2-tertural products and industrial produc butylphenol with chloroform and tion of drugs, pesticides, phero- sodium hydroxide. Jacobson contin mones, and flavor and fragrance ad ues to study other even more hin ditives. Such widely applicable dered catalysts. asymmetric syntheses take on a new Although the new epoxidation importance in light of the regula works well on unsubstituted olefins, tions concerning marketing of enan it seems to work best on olefins that tiomeric versus racemic drugs ex have something to get hold of. Japected this spring from the Food & cobsen's highest enantiomeric ex Drug Administration. cess was 93%, attained with the eth-
Asymmetric synthesis takes big step forward
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April 2, 1990 C&EN
H
CeH 5
PF6"
C6H5n-jJ—^IMH
Manganese-containing chiral catalyst
ylene ketal of 2-cyclohexenone in 52% yield. The researchers use a phase-trans fer reaction with 1 to 8 mole-% ep oxidation catalyst and 5% sodium hypochlorite solution with methy lene chloride as the organic phase. No phase-transfer catalyst is needed as long as the aqueous phase is buff ered to pH 9.5. Chemists in industry may find it attractive to try commer cially available 20% solutions of so dium hypochlorite to minimize the volumes of reaction mixtures. Jacobsen's group initially used iodosomesitylene as the oxidant. But sodium hypochlorite is cheaper and gives higher catalyst turnover num bers. (Turnover number is the num ber of moles of product made per mole of catalyst before the catalyst is spent.) Current turnover numbers in Jacobsen's group are 100 to 200. Ja cobsen is investigating the reaction to see what deactivates catalysts. The diamine to make the catalyst was also cheaply available, thanks to a synthesis perfected by organic chemistry professor Elias J. Corey and coworkers at Harvard Universi ty [/. Am. Chem. Soc, 111, 5493 (1989)]. The Harvard chemists react ed benzil, cyclohexanone, ammoni um acetate, and acetic acid to get a diimine, l,4-diazaspiro[4.5]deca-l,3diene. This they reduced with lithi um to an imidazolidine, which they hydrolyzed to racemic 1,2-diamino1,2-diphenylethane. Fractional crys tallization of their tartrate salts re solved the diamines in greater than 99% optical purities. Research Corporation Technolo gies, Tucson, Ariz., is helping the University of Illinois patent the Ja cobsen epoxidation. Stephen Stinson
