Supplement II, 2008

FluoroFlash Products for ®

Synthesis & Separation

F luoroFlash Tags for

Solution Phase Synthesis
FluoroFlash Scavengers
and Reagents
Sigma-Aldrich® and Fluorous FluoroFlash SPE
Technologies, Inc. are partnering
to bring you easier, faster, and Cartridges for
more robust purifications. Fluorous Separations
Simplify Purification with FluoroFlash® Products!
In partnership with Fluorous Technologies, Inc., Sigma-Aldrich® is pleased to offer a wide range of fluorous products that allow
for faster, more robust purifications. By combining fluorous tags with fluorous solid phase extraction (F-SPE), researchers can
quickly and efficiently purify complex chemical mixtures. In this brochure you will find a representative listing of applications and
FluoroFlash® products available through Sigma-Aldrich at research scale to support this important new separation technology.

Non-fluorous

General Concept:
Fluorous chemistry is a novel tagging
and separation technology based on the Fluorous
use of perfluoroalkyl (fluorous) domains. tagging
Fluorous
Fluorous-tagged molecules can be readily separation
separated from non-fluorous molecules
exploiting fluorophilicity.

Fluorous

Features and Benefits Key Applications:

of Fluorous Chemistry: • Medicinal Chemistry
• Complete solution phase chemistry – highly adaptable • Parallel Synthesis
• Orthogonal mechanism of separation – very selective • Combinatorial Chemistry
• Based on fluorinated materials – chemically inert • Catalysis
• Applicable to numerous molecular classes – broad utility • Peptide & Carbohydrate Synthesis
• Compatible with standard lab equipment – easily integrated • Microwave-assisted Organic Synthesis

Useful References:
Besides the information in this brochure, you can learn much more about fluorous techniques at the Sigma-Aldrich website
portal: sigma-aldrich.com/fluorous. There you will find application notes, ChemFiles, a Cheminar™ on fluorous chemistry,
Aldrichimica Acta articles and many other useful references.

Technical Support:
Fluorous Technologies, Inc. may be contacted by phone (412-826-3050) or email
(contact-fti@fluorous.com) to answer any questions you may have about fluorous
products and applications.

sigma-aldrich.com/fluorous Order: sigma-aldrich.com/order Technical service: sigma-aldrich.com/techinfo

FluoroFlash® Tags for Solution Phase Synthesis
FluoroFlash® tags are perfluoroalkyl modified versions of traditional protecting groups familiar to synthetic chemists. These tags
have reactivity profiles very similar to the traditional protecting group, but have the added benefit of providing a phase tag for
purification. FluoroFlash tags are a solution phase alternative to solid phase synthesis strategies. The fluorous-tagged materials
are easily separated from non-tagged components by F-SPE.

Benefits of FluoroFlash Tags: Fluorous BOC protection used in combinatorial synthesis

1) H2N R' O
• Solution phase kinetics CO2H
F17 Boc-ON
CO2H
(55118) EDCI, HOBt NHR'
• Broad reaction compatibility HN N N
THF:H2O 2) F-SPE
F-Boc
• Reaction monitoring by TLC, GC, LC, NMR, etc. 90% F-Boc

• Readily scalable O O
1) TFA R" X
NHR' NHR' 96-member library
2) F-SPE DIPEA
HN N
R"

Application example of a fluorous PMB protecting group used in the multistep synthesis of natural product Radicicol A

1) NaH, Cl3CCN F-PMB 1) Grubbs II cat. F-PMB

OH O F-PMB Br2, NaOMe O
O O
OH B
C8F17 O 2) O F-SPE
O
Br
F17 PMB-OH B O
(97071)
F-SPE

F-PMB F-PMB
O O
1) t-BuLi 1)TBAF
7 steps
2) O Radicicol A
TBDPSO 2) I2, PPh3
O TBDPSO OEOM I OEOM
O O
O O F-SPE O
3) EOMCl
F-SPE
Dakas, P.-Y. et al, Angew. Chem. Intl. Ed. 2007, 46, 6899

Benzyl OH OH
Boc
N Ph Benzyl OH OH
C8F17 O Boc C8F17 N Ph
CN C8F17 O C8F17
Sigma-Aldrich® offers a full line of FluoroFlash tags. Representative examples are shown in the tableCNbelow. FluoroFlash tags are also available in other
Benzyl OH
perfluorocarbon chain lengths. For a Boccomplete listing of Navailable
Ph
products, please visit sigma-aldrich.com/fluorous.
OH
C8F17 O C8F17
CN Benzyl OH Ph OH
Boc iPr Trityl OH Ph Benzyl OH
N Ph Boc Ph OH
Product No. Name Silane Structure
C8F17 SiH O Product No.C F iPrName
NOH Ph Trityl OH Structure Ph
C8F17 iPr C8F817 17 O C8F17
CN Silane SiH OH
55118 F17 Boc-ON O 19563 C8CF817F17
Boc F17
iPr Benzyl-OH
CN Benzyl OH OH
N Ph N Ph C8F17
C8F17 O O C8F17 Ph O C8F17
iPr Trityl OH Ph
CN CN
Silane SiH OH
C8F17 iPr
04537 F17 Silane iPr O
O 672475
CTrityl
8F17 OH
FluoMar F17 Ph
Trityl-OH
SH
Ph Ph
Ph
iPr O Trityl OH
Silane SiH N O
OH FluoMar
Cbz-OSu C8F17 iPrO O Silane SiH SH
OH
C F17 O iPr N
O Cbz-OSuC8F17 C88F17 O O C8F17 Ph
Trityl Ph
C8F17 iPr
O C8OH
F17 O
14944 F17 Cbz-OSu O Silane C8F17 SiH OH
O FluoMar C8F17 iPr
SH FluoMar
N
40829 F17 FluoMar™ C8F17 OH
Cbz-OSu O O O Fmoc-Cl C8F17
OO F17
C8FluoMar O O
SH
O FluoMar S
C8F17 Fmoc-Cl SH
Cbz-OSu N
O O Cbz-OSu C F N
O 672262 8 17 F26
O Fmoc-Cl
O
O
O
97071 F17 PMB-OH C8F17 C6F13 O C6F13 O FluoMarC8F17 O
SH
PMB-OH OH C8F17
Fmoc-Cl N C6F13 C6F13
PMB-OH
Cbz-OSu O O OHO
C8F17 O C8F17 O O
O
C8FC17
8F17 O Cl
Fmoc-Cl O Cl
Fmoc-Cl
C6F13 C6F13
PMB-OH OH
O
C8F17 O C6F13 C6F13 Fmoc-Cl
PMB-OH OH O Cl C6F13 C6F13
PMB-OH OH
O
C8F17 O O
C8and
FluoroFlash reagents and sorbents are products of Fluorous Technologies, Inc. Use of these products may be protected by U.S. Patents 6,156,896; 5,859,247; 5,777,121 F177,060,850. O
O Cl C6F13 C6F13
FluoroFlash is a registered trademark of Fluorous Technologies, Inc. FluoMar is a trademark of Fluorous Technologies, Inc. PMB-OH OH O Cl
O
C8F17 O
O Cl
FluoroFlash® Scavengers and Reagents
FluoroFlash® scavengers and reagents are analogous to solid phase supported scavengers and reagents that are commonly used
in solution phase synthesis strategies. FluoroFlash scavengers, reagents, and their byproducts can be readily removed by F-SPE.

Benefits of FluoroFlash Fluorous Mitsunobu reaction

Scavengers and Reagents: 1) F26 DIAD

(68333) F

• Solution phase kinetics F17 TPP

(07026)
• Precise stoichiometric control OH + F
O I(OAc)2
Propylamine OH DAIB
• Less molar equivalents required per reaction C8F17 NH2
I(OAc)
2) F-SPE
Propylamine DAIB 2 C8F17 I(OAc)
Propylamine DAIB 60% yield, 97% purity
2

C8F17 NH2 C8F17 NH2

C8F17 DAIB C8F17 I(OAc)2
Propylamine
C F NH2
DAIB Benzylamine 8 17I(OAc)2 C8F17
Sigma-Aldrich offers a full line of Propylamine
FluoroFlash scavengers and reagents. Representative examples are shown
I(OAc)2
in the table below.
C8F17
Propylamine NH2 DAIB NH2
C8F17 Tin Hydride SnH3
For a complete listing of available products, pleaseCvisit
Benzylamine
F
8 17
sigma-aldrich.com/fluorous.
NH2
Benzylamine C4F9
NH2 C8F17 C8F17 3
Tin HydrideBenzylamine
DAIB SnHI(OAc)
3 2 NH2 Tin Hydride SnH3
Propylamine C4F9
C8F17 C4F9
3
Product No. Name Benzylamine StructureNH2
C8F17 ProductC No. C8F17 Name NH2 Tin Hydride Structure 3SnH3
8F17
DAIB I(OAc)2 Tin Hydride C4F9
Propylamine C8F17 3
04636 F17 Propylamine Benzylamine NH2 Tin Hydride 06694 SnH3 F27 Tin Hydride Triphenyl SnH PPh2
C8F17 NH2 C4F
NH C9F
Thiol
8 17 SH Phosphine C4F9
C8F17 2 Tin Hydride 3 C F SnH3 3
C4F9 8 17 PPh2
Benzylamine C F Triphenyl C8F17 PPh2
3 Triphenyl
07856 F17 Benzylamine Thiol 8 17 SH Phosphine Thiol SH Phosphine
C8F17 NH2 07026 C8F17 C8F17F17 Triphenylphosphine
Tin Hydride SnH 3 Triphenyl C8F17 PPh 2
Benzylamine C F
C8F17 ThiolIsatoic 4 9 3 SH Phosphine
CPPh
8F172
NH2 Triphenyl Tin Hydride Anhydride
SnH3 DIAD
C8F17
C6F13 C6F13
Thiol SH Phosphine PPh2
Isatoic
C8F17 Triphenyl C4F9
08686 F17 Thiol AnhydrideC8F17
Thiol SH C8F17 Isatoic 3 N C8F17
Phosphine C6FAnhydride
C8F17 DIAD 68333 13
C8F17
F26
O
CDIAD
O
6F13
O DIAD C F
6 13
O O C F
6 13
N C8F17 Isatoic O O
Triphenyl PPh N2 C8F17
Anhydride O O
Thiol O SH Phosphine DIAD C6F13 O NO N C6F13
07172 F17 Isatoic Anhydride Isatoic C8F17 O O O O O ON O
C8F17 C8F17 O O
Anhydride N NC6F13
Isatoic DIAD C6F13
Triphenyl PPh2 ON ON
Anhydride N CSH O O O
Thiol 8F17 Phosphine O O
C8F17 DIAD C6F13 C6F13
OC8O N N
Isatoic O O O N C8F17 672378 Ethyl
F17
O Isocyanate O
F26 CDMT CDMT
O O NCO C6F13 O
Anhydride O O O N N C8FO
Ethyl DIAD C6FEthyl
13 O 17 C6F13
18486 F17 Ethyl Isocyanate Isocyanate N NCO C8F17 CDMT C6F13 N N O N N
Isatoic Isocyanate CDMT C6F13 O
C8F17 O CO8F17 NCO
Anhydride Ethyl C6F13 O N Cl
O O O DIAD CIsocyanate
F
6 13 O N O N C F
6 13 CDMT NO N
NCO C6F13
Ethyl N C8F17 N CN8F17
C6F13 O N Cl
16429
Propylamine F17 DAIB DAIB
Isocyanate
O
I(OAc) 2CDMT C6F13 OO O C F
6 13 O N N N Cl
Ethyl NCO O O O O
C8F17 CDMT
C8F17 NH2 Isocyanate C6FN 13 N N O
N C6F13 O N Cl
C8F17 NCO
C8F17
Ethyl C6F13 O N N
Cl N
Isocyanate CDMT C F O
C8F17
NCO C6F13 6 13 O N Cl
Benzylamine Ethyl N N
Isocyanate CDMT C 6 F 13 O
NH2 NCO C6F13 O N Cl
Tin Hydride C8F17 SnH3
C4F9 N N

Other Fluorous Technologies Products

C8F17 3
Fluorous
C6F13
propylamine O N
used Cl
as a scavenger

available through Sigma-Aldrich® PPh2

NCO 1) benzylamine (1.0 equiv) H
N NHBn
Triphenyl
Thiol SH 2) F17 propylamine (1.0 equiv)
• Fluorous Creagents
F 8 17 for Proteomics and Metabolomics
C F
Phosphine O
8 17 (04636)
Applications 1.3 equiv.
3) F-SPE 93% yield, >98% purity
• Additional
Isatoic
Anhydride
FluoroFlash tags for Protecting Group chemistry
DIAD C F C F Lindsley, C.W. et al, Tetrahedron Lett. 2002, 43, 4225
• FluoroFlash products N Cfor
F Fluorous Peptide &
8 17
6 13 6 13

O O
Carbohydrate O O Synthesis
O O O
N N
• Expanded FluoroFlash Tin, Phosphine, Catalyst,
and Ligand offerings
Ethyl
IsocyanateFlash Tags for Fluorous
• Fluoro CDMT Mixture CSynthesis
F O 6 13
NCO
C F
• FluoroFlash Building Blocks to Design Your Custom
8 17
N N

Fluorous Tags C F O N Cl 6 13

For more details, please visit sigma-aldrich.com/fluorous

FluoroFlash® SPE Cartridges for Fluorous Separations
The separation of fluorous compounds from non-fluorous compounds using FluoroFlash® silica gel is the central theme
of fluorous techniques. Fluorous solid phase extraction (F-SPE) is used for quick separations of reaction mixtures involving
FluoroFlash tags, scavengers, and reagents. The separation of fluorous compounds by F-SPE is a reliable and generic procedure
that resembles filtration more than chromatography. The facile separation depends primarily on the presence or absence of a
light fluorous tag, not polarity or other molecular features that control traditional chromatography.

A simple two-step separation involves the loading of a reaction mixture containing the fluorous-tagged molecule onto an F-SPE
cartridge, washing the non-fluorous compounds away using a fluorophobic wash (typically 80:20 MeOH:water), then washing off
the fluorous compounds with a fluorophilic wash, such as MeOH or THF. No fluorous solvents are necessary. The cartridge can be
regenerated by washing with acetone or THF. Loading capacity for F-SPE cartridges is between 5-15% by weight of fluorous silica gel.

Fluorous Solid Phase Extraction Dye Demonstration

A visual representation of the FluoroFlash solid phase extraction technique illustrates
the easy separation of a fluorous-tagged product from the non-fluorous compounds
through the use of colored dyes.
• A mixture of a non-fluorous dye and a fluorous dye is loaded onto the F-SPE cartridge
• Non-fluorous dye is washed off with a fluorophobic solvent wash, 80:20 MeOH:water.
(middle test tube)
• Fluorous dye is washed off with a fluorophilic solvent wash, MeOH. (right test tube)

A detailed F-SPE Application Note can be found at the Sigma-Aldrich® website portal:
sigma-aldrich.com/fluorous.

Benefits of FluoroFlash SPE Sigma-Aldrich offers FluoroFlash silica gel in pre-packed cartridges, in bulk,
or as TLC plates.
separations:
Product No. Product
• High selectivity 14196 Pack of 20
FluoroFlash SPE cartridges, 2 g, 8 cc tube
• Simple binary separation
00866 FluoroFlash SPE cartridges, 5 g, 10 cc tube Pack of 10
• Large loading capacity
08967 FluoroFlash SPE cartridges, 10 g, 60 cc tube Pack of 5
• No fluorous solvents needed
08966 FluoroFlash SPE cartridges, 20 g, 60 cc tube Pack of 2
• Cartridges recyclable up to 10 times
06961 FluoroFlash SPE cartridges, 20 g, 60 cc tube Pack of 5
• Automation compatible
08965 FluoroFlash Silica Gel, 40 micron particle size 100 g

16888 FluoroFlash TLC Plates with F254 indicator Pack of 10

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