If you have been trying to reach us at FTI earlier this week, you may have had a difficult time. Unfortunately, we had an unexpected power outage within the research park where we are situated which shut us down for two days. Things are now back to normal however and we are fully capable of helping solve your separation problems or advising you on fluorous applications.
Thank you for your understanding.
Aryloxyamines are an interesting class of compounds which have been used in a variety of applications. They are excellent intermediates for the synthesis of a number of biologically active heterocycles. They also readily form very stable oximes and have therefore been used in several chemical ligation strategies for application in fragment based discovery, dynamic combinatorial libraries, and chemical biology applications. However, there is only a limited number of commercially available aryloxyamines and no methods for the parallel synthesis of these compounds have been reported. Until now.
A new publication from Prof. Philippe Durand in J. Comb. Chem. describes a fluorous tagged approach to the parallel synthesis of these useful compounds. The paper highlights some of the virtues of fluorous chemistry. Of primary importance in this instance is the solution phase nature of the chemistry and the inertness of the tag. This allowed the researchers to test and apply a number of conditions that failed in solid phase approaches. Application of various Petrassi coupling conditions to a solid-supported N-hydroxyphthalimide failed as did the use of a ROMP based strategy. By combining the solution phase chemistry of a fluorous tag with the ease of fluorous solid phase extraction (FSPE), the authors were able to develop a general synthetic methodology amenable to parallel synthesis.
The route is shown above and uses modified Petrassi conditions for the coupling of the fluorous tagged N-hydroxyphthalimide with arylboronic acids. Their initial efforts using standard Petrassi conditions afforded only modest yields (40-60%). Optimization of the reaction conditions was conducted using a multi-variable design of experiments (DoE) based on Taguchi methods. This allowed them to identify which variables, or combinations of variables, were most important. This led to conditions which used 4 equivalents of the boronic acid, Cu(OAc)2 as catalyst, and benzotrifluoride (BTF) as solvent. Of course, using that much excess arylboronic acid also led to increased amounts of by-products and that’s where the fluorous tag comes in. The researchers developed their own unique FSPE protocol involving three different fluorophobic washes to remove the various by-products followed by a single fluorophilic wash with acetone to isolate the arylated hydroxyphthalimide 3 in generally excellent yield and purity. Aminolysis of 3 to provide the desired aryloxyamines was conducted using resin-bound amine. The authors noted that they could perform the aminolysis with methylamine then collect the products using FSPE. However, the volatility of some of the products made isolation from the fluorophobic wash difficult. No problem. The solution phase nature of the fluorous tag made the use of the resin-supported amine in a volatile solvent easy, once again showing how versatile the fluorous tag can be. The authors went on to produce 25 different aryloxyamines.
An interesting communication which highlights some of the advantages and adaptability of fluorous tagged methods to meet the needs of a specific chemical scheme.
At this year’s Fall ACS National Meeting, Prof. Nicola Pohl of Iowa State University will be awarded the Horace S. Isbell Award for “excellence in and promise of continued quality of contribution to research in carbohydrate chemistry”. An integral part of her research program has been the use of fluorous tags in automated carbohydrate synthesis and immobilization of those carbohydrates via the same fluorous tags. We are pleased to extend our congratulations to Prof. Pohl.
With this award, Prof. Pohl joins an ever expanding group of scientists who have been recognized for their work in fluorous chemistry. Fluorous Technologies Inc. founder and University of Pittsburgh professor Dennis Curran was the recipient of the 2008 ACS Award for Creative Work in Fluorine Chemistry. Prof. István Horváth was a 2006 Humboldt Research Award winner for his pioneering work in fluorous chemistry. Our own Yimin Lu was honored in 2006 by the Organic Division of the ACS with a Technical Achievement Award.
Beyond those who have been specifically recognized for their work in fluorous chemistry, however, are the numerous award-winning scientists who have used fluorous methods in their research. Prof. Peter Seeberger, the 2009 recipient of the ACS Carbohydrate Division’s Charles S. Hudson Award among many other accolades, has published several papers using fluorous methods in both carbohydrate and peptide chemistry. Staying within the ACS Carbohydrate Division, Prof. Xuefei Huang was last year’s recipient of the New Investigator Award. Prof. John Porco who has used fluorous reagents in several library syntheses was named an Arthur C. Cope Scholar last year, while Prof. Mukund Sibi who has utlized fluorous tags in his free radical research was bestowed that same honor in 2008. Prof. Veronique Gouverneur was awarded the Royal Society of Chemistry’s 2008 Bader Award for her work in fluorine chemistry, which includes the use of fluorous tags and reagents. A different Bader Award, this one for bioorganic or bioinorganic chemistry, was given to Prof. Stuart Schreiber in 2000. Prof. Schreiber’s group has published one of preeminent papers on fluorous microarrays.
These are just a few recent examples of distinguished researchers that have used fluorous methods as part of their work. Research that has been recognized and valued by peers. We at Fluorous Technologies are genuinely honored to have played a role, no matter how small or large, in helping these and other scientists around the world advance their research.
The 2010 ACS Fall National Meeting will be held in Boston from August 22-26th, 2010. The following is a list of presentations that we have located using the ACS Online Technical Program which include fluorous in the abstract. An upcoming Fluorous Technical Newsletter will provide context and commentary for many of these presentations.
Please be aware that this may not be a complete list of presentations using fluorous chemistry since the online search only identified those presentations with “fluorous” in the title or abstract. If you are presenting at the meeting and would like your presentation to be added, please contact us and we can add it. Also note that poster 96 will be available for viewing at two sessions, hence the double listing.
To read the abstracts, please click on the titles.
1. 96 – Synthesis of a fluorous tagged disaccharide for the enzymatic preparation of heparin oligosaccharides.
Authors: Sayaka Masuko, Smritilekha Bera, Robert J. Linhardt
Date/Time: Monday, August 23, 2010 - 08:00 PM
Session info: Sci-Mix (08:00 PM – 10:00 PM)
Location: Boston Convention & Exposition Center, Hall C
2. 96 – Synthesis of a fluorous tagged disaccharide for the enzymatic preparation of heparin oligosaccharides.
Authors: Sayaka Masuko, Smritilekha Bera, Robert J. Linhardt
Date/Time: Wednesday, August 25, 2010 - 08:00 PM
Session info: General Posters (08:00 PM – 10:00 PM)
Location: Boston Convention & Exposition Center, Hall C
3. 604 – Recyclable fluorous organocatalysts for asymmetric synthesis
Authors: Zijuan Zhang, Liang Wang, Hong Zeng, Wei Zhang
Date/Time: Tuesday, August 24, 2010 - 08:00 PM
Session info: Asymmetric Reactions and Syntheses, Biologically- Related Molecules & Processes, Material, Devices & Switches and Peptides, Proteins & Amino Acids (08:00 PM – 10:00 PM)
Location: Boston Convention & Exposition Center, Hall C
4. 162 – Fluorous benzaldehyde based synthesis of heterocyclic systems
Authors: Asha Kadam, Shang Ding, Ryan Fitzgerald, Minhgiao Le-Nguyen, Wei Zhang
Date/Time: Sunday, August 22, 2010 - 08:00 PM
Session info: Heterocycles and Aromatics, Metal-Mediated Reactions & Syntheses, Molecular Recognition & Self-Assembly and Physical Organic Chemistry: Calculations, Mechanisms, Photochemistry & High-Energy Species (08:00 PM – 10:00 PM)
Location: Boston Convention & Exposition Center, Hall C
5. 983 – Fluorous benzaldehyde based multi-component reactions for heterocycles
Authors: Bruno Piqani, Shan Ding, Tao Xi, Wei Zhang
Date/Time: Wednesday, August 25, 2010 - 07:00 PM
Session info: Chemistry for Preventing & Combating Disease, New Reactions & Methodology and Total Synthesis of Complex Molecules (07:00 PM – 10:00 PM)
Location: Boston Convention & Exposition Center, Ballroom
6. 532 – Fluorous linker facilitated synthesis of heterocyclic systems
Author: Wei Zhang
Date/Time: Tuesday, August 24, 2010 - 02:20 PM
Session info: Heterocycles and Aromatics (01:00 PM – 05:20 PM)
Location: Boston Convention & Exposition Center, Room 203
7. 1083 – Fluorous mixture synthesis and spectroscopic analysis of the phytophthora mating hormone a1 and the corresponding bis-MTPA esters
Authors: Reena Bajpai, Dennis P. Curran
Date/Time: Wednesday, August 25, 2010 - 07:00 PM
Session info: Chemistry for Preventing & Combating Disease, New Reactions & Methodology and Total Synthesis of Complex Molecules (07:00 PM – 10:00 PM)
Location: Boston Convention & Exposition Center, Ballroom
8. 485 – Surface modification of poly(dimethylsiloxane) with perfluorinated alkoxysilanes: Zeta potential and the adsorption of perfluoro-tagged proteins and peptides
Author: Hugh Horton
Date/Time: Thursday, August 26, 2010 – 4:25 PM
Session info: Symposium in Honor of Richard Lambert (1:30-4:50 PM)
Location: Westin Boston Waterfront, Harbor Ballroom II
9. 89 – Di-fluorous tagging strategy for the automated solution-phase synthesis of plant oligosaccharides
Author: Sahana Nagappayya, Heather Edwards, Nicola Pohl
Date/Time: Sunday, August 22, 2010 – 2:00 PM
Session info: New Reactions and Methodology (1:00 – 5:20 PM)
Location: Boston Convention & Exhibition Center, Room 206A
10. – Arrays and automated oligosaccharide synthesis
Date/Time: Sunday, August 22, 2010 – 4:10 PM
Author: Nicola Pohl
Session info: Wolfrom-Isbell-New Investigator Award Symposium (1:00 – 4:45 PM)
Location: Boston Convention & Exhibition Center, Room 251
11. 408 – Oxidation of olefins with hydrogen peroxide and polyoxometalates in ionic liquids and fluorinated alcohols as “magic solvents”
Authors: Mauro Carraro, Serena Berardi, Martino Gardan, Marcella Bonchio, Gianfranco Scorrano, Andrea Sartorel
Date/Time: Tudsday, Aogust 24, 2010 – 9:20 PM
Session info: Organometallic Chemistry (9:00 – 11:25 AM)
Location: Boston Convention & Exhibition Center, Room 257B
12. 919 – Tuning optical and electronic properties of arenebased organic semiconductors via perfluoroalkylation
Author: Haoran Sun, Michael Billion
Date/Time: Wednesday, August 25, 2010 – 5:00 PM
Session info: Material, Devices and Switches (1:00 – 5:25 PM)
Location: Boston Convention & Exhibition Center, Room 207
An interesting paper from 3 groups in Germany published in ChemPhysChem describes the formation of micron-bubbles using fluorous-fluorous aggregation. The researchers first formed fluorous tagged polyglycerol dendrimers. These dendrimers then have a hydrophilic core with fluorous shell around them. They were found to have very little solubility in organic solvents, but were soluble perfluorinated solvents. When a fluorous tagged dye, however, is added and the mixture subjected to ultrasonication the dendrimers are then soluble in a wide range of organic solvents, even highly fluorophobic ones such DMSO. The authors propose that the fluorous tagged dye and the fluorous dendrimer self-assemble through fluorous interactions. This turns the dendrimer with a fluorous shell into a dendrimer complex with a second polar shell around the fluorous shell.
It doesn’t end there, however. The fluorous domains on the dendrimers are obviously capable of complexing with each other. The complexes formed in the presence of the dye self-assemble with each other to form micron-bubbles. The average diameter of the bubbles could also be tuned. When the complexes are formed the amount of complexation could be estimated by 19F NMR. The more complexation observed, the smaller average diameter of the micron-bubbles. They also propose the these micron-bubbles consist of air, a dendrimer layer and a dye shell since they found that degassing led to bubble collapse, but that the bubbles could be reformed by gassing.
This is another example of the use of fluorous partitioning in order to form supramolecular complexes. I’ll call it micro-phase formation. There’s plenty of examples of nanoparticle formation based on “fluorous interactions”. One application using these nanoparticles was published last year for DNA detection that we commented on. In that example, gold nanoparticles contained a DNA sequence complementary to a target sequence. A second complementary sequence with a fluorous tag was introduced. The nanoparticles with the target sequence thus became fluorous and aggregated causing a color change which indicated the presence of the target DNA sequence.
