| If your email does not support graphics, please access the web version of this technical bulletin. |
|
New Fluorous Research from Around the World
A variety of new fluorous-tagged compounds have recently been developed. Purification of the associated reactions was greatly simplified - the key benefit of fluorous chemistry - and in one interesting case discussed below, addition of a fluorous tag improved the physical properties of a thiol by reducing its odor. Interest in fluorous-tagged biopolymers remains strong, and new work has also been reported in fluorous catalysis.
FLUOROUS PROTECTING GROUPS: A new
acid-labile fluorous protecting group was recently synthesized by Dr.
Ladlow and colleagues at the GlaxoSmithKline Cambridge Technology Centre [1].
They improved the purification of sulfonamide and carboxamide libraries
by introducing the fluorous phase-tag. Following Suzuki-Miyaura coupling, fluorous SPE was
used for rapid separation. High (>95%) purity was achieved without column chromatography - avoiding an expensive step that is often a
bottleneck in library purification. Their work is also one of a number of recent examples of a
rapid-synthesis workflow incorporating
both a microwave-promoted reaction (in this case, the coupling step) and an "in-line"
parallel fluorous separation.
A prominent research group at The Noguchi Institute also prepared a novel fluorous
protecting group, Bfp-OH, for use in pentasaccharide synthesis [2]. The Bfp-OH was used as a fluorous support in a solution-phase system,
and each intermediate was isolated by liquid-liquid extraction. Following cleavage, the fluorous species was readily
removed and recycled. Like GSK, the Noguchi researchers noted that the requirement for column chromatography was minimized.
Highly fluorous thioglycosyl donors were prepared from a new, nearly odorless fluorous thiol reagent at the University of Toledo. This fluorous thiol was developed by Dr's Huang & Jing with the specific aim of mitigating the unpleasant odor typical of thiols. Subsequent glycosylations of primary and secondary alcohols using this fluorous thioglycosyl donor produced product in high yields (85-95%). The fluorous disulfide by-product was easily removed by F-SPE and the fluorous thiol was regenerated for re-use [3]. An additional tagging application involved the use of fluorous-tagged saccharide primers. Researchers at the University of Tokyo found that these primers could be viable scaffolds for fluorous-enhanced synthesis of oligosaccharides, noting that the fluorous-tagged saccharide could actually be taken up by a cell. Once in the cell, the chain was elongated by cellular enzymes and released into the culture media. The presence of fluorine in the cells appeared to have no adverse effect. Their presence may have increased the hydrophobicity of the primer and actually enhanced membrane permeability [4].
FLUOROUS CATALYSIS: Researchers at Kyoto University developed a fluorous chiral phase-transfer catalyst for use in the catalytic asymmetric synthesis of chiral α-amino acids. This recyclable fluorous catalyst was used in the alkylation of a glycinate Schiff base with alkyl halides, and then recovered using fluorous solvent [5]. In another catalytic asymmetric reaction, enantiopure fluorous (bis)oxazolines with fluorine content >50% were synthesized. This work was completed at the Universite Claude Bernard Lyon and involved the introduction of two fluorinated ponytails by alkylation of the corresponding non-fluorous (bis)oxazolines. Enantioselectivity exhibited by these fluorous ligands was quite close to that observed in the non-fluorous analogues. The fluorous ligands were again easily recovered and reused with no degradation in performance [6]. Finally, Prof. Dr. Paul Knochel reported a new fluorous benzimidazolic ligand for ruthenium catalyzed fluorous biphasic epoxidation of alkenes with oxygen. The reaction rates and yields were excellent while the fluorous species was recycled up to ten times without any loss of activity [7].
PRODUCT AVAILABILITY: Fluorous Technologies stocks a wide variety of fluorous compounds, including protecting groups, catalysts, and precursors. FTI also offers custom development and separation services.
Speeding up Synthesis & Separation: Microwave Synthesis and Fluorous Chemistry
Fluorous chemistry is widely compatible with existing and emerging synthetic techniques. In an effort to develop high-speed, high-productivity workflows, FTI researchers have recently demonstrated the use of microwave-promoted reactions with fluorous-enhanced separations. FTI has published several papers on the topic and recently received an SBIR grant to continue developed work on rapid synthesis.
- “A traceless perfluorooctylsulfonyl tag for deoxygenation of phenols under microwave irradiation”; Zhang, W.; Nagashima, T.; Lu, Y.; Chen, C. H.-T. (Tetrahedron Letters 2004, 45, 4611-4613)
- “A Highly Efficient Microwave-Assisted Fluorous Suzuki Coupling Reaction”; Zhang, W.; Chen, C. H.-T.; Luo, Y.; Nagashima T. (Organic Letters 2004, 6, 1473-1476)
- “Combination of Microwave Reactions with Fluorous Separations in the Palladium-Catalyzed Synthesis of Aryl Sulfides” Zhang, W.; Lu, Y.; Chen, C. H.-T. (Molecular Diversity, 2003, 199-202)
The Handbook of Fluorous Chemistry
"The Handbook of Fluorous Chemistry", edited by the pioneers of fluorous research, John A. Gladysz, Dennis P. Curran and Istvan T. Horvath has just been published by Wiley. This handbook is the first to summarize all the essential aspects of this emerging field of chemistry. A partial listing of the chapters includes:
- Fluorous Chemistry: Scope and Definition
- Fluorous Solvents and Related Media
- Separations with Fluorous Silica Gel and Related Media
- Getting Started in Synthesis: A Tabular Guide to Selected Monofunctional Fluorous Compounds
- Applications of Fluorous Compounds in Materials Chemistry
A link to the ordering information can be found on
FTI's homepage.
Fluorous SPE Application Note Revised
Our Fluorous SPE Application Note has been updated and expanded. This and other application notes are on our website. It now includes recommended procedures for pre-treatment of the cartridges prior to use, and for washing prior to re-use. An FAQ list has also been added. The updated application note is available at www.fluorous.com/download/an_spe.pdf. As always, if you have specific questions or need additional information, please feel free to contact us at any time by email or phone at 412-826-3050.
Academic offer: Free fluorous chemistry lecture slides
For our colleagues in the academic community, FTI is pleased to provide a set of PowerPoint lecture slides on fluorous chemistry. The presentation is scientific rather than commercial in nature, and it is intended to be a teaching aid for instruction on fluorous chemistry mechanisms, techniques, and applications. The release date is set for 30 August. Please call us to arrange to receive these slides at no cost or obligation to you.
References Cited in August 2004 Technical Bulletin:
[1] Ladlow, Mark, Warrington, Brian H., Villard, Anne-Laure. Journal of Combinatorial Chemistry 2004, 6(4), 611-622
[2] Miura, Tsuyoshi; Goto, Kohtaro; Waragai, Hideki; Matsumoto, Hiroharu; Hirose, Yuriko; Ohmae, Masashi; Ishida, Hideki; Satoh, Ai; Inazu, Toshiyuki. Journal of Organic Chemistry 2004, 69(16), 5348-5353
[3] Huang, Xuefei, Jing, Yuqing. Tetrahedron Letters 2004, 45(24), 4615-4618
[4] Kasuya, Maria Carmelita Z.; Cusi, Reuben; Ishihara, Orie; Miyagawa, Atsushi; Hashimoto, Kazuhiko; Sato, Toshinori; Hatanaka, Kenichi. Biochemical and Biophysical Research Communications 2004, 316(3), 599-604.
[5] Shirakawa, Seiji; Tanaka, Youhei; Maruoka, Keiji. Organic Letters 2004, 6(9), 1429-1431.
[6] Bayardon, Jerome; Sinou, Denis. Journal of Organic Chemistry 2004, 69(9), 3121-3128.
[7] Ragagnin, Gianna; Knochel, Paul. Synlett 2004, (6), 951-954.