SCIENCE & TECHNOLOGY nine. He says that the compound is easy to make and is stable at room temperature and open to the air. J. Stewart Witzeman, who is technology director of Eastman's newly erected performance chemicals and intermediates business, underscored the compound's stability and proprietary status when he said prior to the CPhI Conference: 'This exciting discovery, made in Eastman's research laboratories, has stirred tremendous interest in the pharmaceutical community Now researchers have a potential new path to produce new active pharmaceutical ingredients more quickly and cost effectively, while being confident in Eastman's ability to provide sufficient quantities of chiral ligands at any scale required." Michel Bulliard, who is research and development manager at PPG-SIPSY in Avrille, France, was at CPhI to show off his own firm's efforts to declare independence in intellectual property Speaking to the Chiral Technology Conference running alongside the show, he said that the company originally licensed a ligand called MeOBiphep from Roche of Basel, Switzerland, in 1987 The compound is 2,2'-bis(iphenylphosphino)-6,6'-dimethoxybiphenyl. But PPG-SIPSYhas gone on to modify the structure in order to make it the company's own. One version is called SoniPhos, with 6,6'-acyloxy groups. This version is superior for ruthenium-catalyzed reductions of ethyl 7-chloroacetoacetate, Bulliard says. Another version has methoxy groups in the 4-, 5-, and 6-positions of each biphenyl ring. That ligand works best on hydroxyacetone. Bulliard says these and other variations allow PPG-SIPSY to vary
CHIRAL CATALYSIS RIDING HIGH Innovations in enantioselective catalysis stand out among new technologies at CPhI in London STEPHEN C. STINSON, C&EN NORTHEAST NEWS BUREAU
A
CURRENT OF EXCITEMENT R I P -
pled through the London exposition hall, the site of this year's Conference on Pharmaceutical Ingredients (CPhI), when the winners of the Nobel Prize in Chemistry were announced the week of Oct. 8. The prize, which this year recognizes enantioselective catalysis, went to retired Monsanto chemist William S. Knowles and organic chemistry professors K. Barry Sharpless of Scripps Research Institute and Ryoji Noyori of Nagoya University, in Japan. The names of the Nobel winners resonated in the expo hall, where a strong trend among the booths was innovation in enantioselective catalysts. Indeed, Noyori's prize underscored an irony behind all of the catalytic innovation at CPhI. Among Noyori's achievements is the invention of BINAP {2,2'-bis(diphenylphosphino)-l,r-binaphthyl} in 1983. Nagoya University patented that catalyst ligand and licensed the patent toTakasago International Corp. of Tokyo. Takasago used a rhodium chelate of BINAP to develop a process to make synthetic /-men-
thol, whose production is now 2.6 million lb per year. So successful was the BINAP ligand in the menthol and other enantioselective processes that other companies asked Takasago for sublicenses. Takasago refused. Takasago's refusal served as awake-up call that other fine chemicals firms must develop their own proprietary catalyst ligands so as not to be left behind at the dawn of enantioselective technology in drugs and fine chemicals. PERHAPS THE NEWEST such ligand to emerge in this drive for ligand self-sufficiency is BoPhoz from Eastman Chemical. The compound takes its trade name from its inventor, Neil W Boaz, a senior research associate who was at CPhI to promote BoPhoz, and from its diphenylphosphino groups. Boaz says that Eastman will either sell the ligand with a license for its use or use the catalyst in-house to make singleenantiomer products to special order. Boaz tells C&EN that the ligand has already seen commercial application at Eastman, which uses it in an asymmetric hydrogenation to make cyclopropyl-a-ala-
CATALYST LIGANDS New entries for self-sufficiency CH3 Fe P(C6H5)2P(C6H5)2 BoPhoz (N-ethyl shown)
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TaniaPhos (one form shown)
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Josiphos (one form shown)
DepyPhos
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OCTOBER
29, 2001
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SCIENCE & TECHNOLOGY the dihedral angle between the twisted biphenyl rings and the cone angle, which is a measure of the angle of"bite" of the phosphorus atoms on the transition-metal ion. OM Group of Cleveland acquired a stable of enantioselective phosphorus hydrogenation catalyst ligands plus expertise in precious metals with its purchase ofthe dmc2 (formerly standingforDegussa metals, chemicals, and ceramics) division ofDegussa. Previously OM's business was limited to catalysts and additives based on nonprecious transition metals, notably cobalt and nickel The ligands from OM's dmc2 division in HanauWolfgang, Germany, are DepyPhos, a bis(diphenylphosphino)pyrrolidine, and MandyPhos andlaniaPhos, which are each a series ofsubstitutedferrocenesthat include diphenylphosphino groups. DSM FINE CHEMICALS has followed a course ofboth licensing and developing its own enantioselective catalyst ligands. The company inherited a licensing agreement with Pennsylvania State University with its acquisition of Catalytica ofMountain View, Calif. The license is on two ligands called PennPhos and BICP, invented by associate
Heterocyclics From Nitrogen to Sulphur containing heterocycles
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Ubichem pic
