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FTI, Mettler Toledo, & CEM Seminar Summary

On October 2nd, chemists from 30 leading pharmaceutical and academic labs convened in New Jersey to discuss how fluorous chemistry, automated parallel synthesis, and microwave synthesis can be combined to create an integrated solution for increasing lead generation and optimization of drug candidates. If you missed the seminar, please see the informative presentations below, available as ftp downloads.

Dr. Craig Lindsley of Merck Research Labs presentation (157 KB PDF)

Dr. Neil Moorcroft of Aventis Pharmaceuticals presentation (875 KB PPT)

Dr. Aaron Beeler of Boston University presentation (256 KB PDF)

Dr. Marvin Yu of Fluorous Technologies presentation (437 KB PDF)

Fluorous Technologies Licenses Palladium Microwave Patent from Personal Chemistry

The licensed patent covers new means for performing Heck, Stille and Suzuki reactions catalyzed by palladium (except Pd/C), utilizing microwave energy. FTI has demonstrated that FluoroFlash® reagents are ideal for rapid microwave synthesis followed by expeditious fluorous purification

In this example, a commercially available phenol is converted to a sulfonate by reacting with C8F17 perfluorosulfonyl fluoride (F-Sulfonyl Fluoride). Similar conditions used in traditional thermal Suzuki couplings are applied to the microwave reaction with these exceptions: the reaction temperature is higher (100ºC) and the reaction time is much shorter (10 min). Fluorous solid-phase extraction is employed to separate the coupling product from the cleaved fluorous tag. In a typical "flash fluorous synthesis" under microwave conditions, a chemist can finish the whole process including reaction, purification, and product characterization in less than one hour.

Run under license to US patent 6,136,157 and European patent No. 0901 453 held by Personal Chemistry

Fluorous Tagged Amino Acids at Work

In a recent publication, Professor Dennis Curran and co-workers showed how Fluorous carbobenzyloxy (F-Cbz) tagged amino acids can be used to create FCbz-Phe derivatives. Several reactions of the phenylalanine derivatives were undertaken to show the broad applicability of the FCbz-tagged amino acids and to validate that high purity products would result upon separations over FluoroFlash® silica gel. Coupling reactions were conducted with four different amines under standard conditions (EDCI, HOBt) as shown in Table 2. The amines were used in excess (4 equiv) and the excess amine and the crude coupled products were isolated in moderate to excellent yields and high levels of purity by either FluoroFlash® SPE or FluoroFlash® HPLC.

D. P. Curran and Co-workers, "Synthesis and Reactions of Fluorous Carbobenzyloxy (fCbz) Derivatives of a-Amino Acids" Journal of Organic Chemistry 2003, 68, 4643-4647 [Abstract] [Full Article]

FTI Releases Two New Products

Fluorous benzophenone imine (product number F017069) is a useful ammonia equivalent in the palladium catalyzed amination of aryl halides and triflates. The intermediate N-aryl benzophenone imines can be purified by F-SPE and converted to amines by hydrolysis. The fluorous benzophenone byproduct can be easily removed from the mixture by F-SPE, yielding pure amines.

The Bis fluorous triphenylphosphine palladium complex (product number F034092) is a useful catalyst in Stille and Suzuki couplings. After the reaction, the catalyst can be rapidly removed from the reaction mixture by F-SPE. Currently, work is being done at FTI to integrate this catalyst with microwave techniques. This would offer another route to a "Flash Fluorous Synthesis", where the reaction, purification, and characterization are all finished within 1 hour."

Cutting Edge Fluorous Chemistry

In a recent publication, Joji Nishikido and co-workers at The Noguchi Institute used several catalysts in a fluorous biphasic catalytic system for Baeyer–Villiger oxidations.

Sn[N(SO2C8F17)2]4 was shown to give an excellent yield and selectivity of cyclic ketones by using 35% aqueous hydrogen peroxide. Furthermore, the catalyst was completely recovered and reused in the fluorous immobilized phase without loss of activity. Even after recycling the catalyst four times, the GC yield still remained higher than 90%.

Catalytic recycling of Sn[N(SO2C8F17)2]4 was also tested in the BV oxidation of cyclobutanone. It was found that there was almost no difference in the formation rate of gamma-butyrolactone (no loss of catalyst activity).

Xiuhua Hao, Osamu Yamazaki, Akihiro Yoshida and Joji Nishikido, TETRAHEDRON LETTERS 2003, 44:27:4977 - 4980. [Abstract]

Fluorous Technologies, Inc. (FTI) is a chemical technology company dedicated to the development and commercialization of fluorous products focused at the life science market. The company uses patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. FTI further leverages its enabling technology through service contracts, licenses, and collaborations.

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