Cocatalysis by tetravalent tin compounds in phase-transfer catalyzed fluorination of alkyl halides and sulfonates

Article abstract of DOI:10.1016/S0040-4039(02)00376-3

Phase-transfer catalyzed fluorination of alkyl halides or sulfonates is co-catalyzed efficiently by triorganotin halides. The cocatalytic action is due to continuous formation of lipophilic hypervalent triorganodifluorostannate anions, which act as fluori

Full text of DOI:10.1016/S0040-4039(02)00376-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2761–2763
Cocatalysis by tetravalent tin compounds in phase-transfer
catalyzed fluorination of alkyl halides and sulfonates
Mieczysław Ma˛kosza* and Robert Bujok
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw 42, POB 58, Poland
Received 7 January 2002; revised 12 February 2002; accepted 21 February 2002
Abstract—Phase-transfer catalyzed fluorination of alkyl halides or sulfonates is co-catalyzed efficiently by triorganotin halides.
The cocatalytic action is due to continuous formation of lipophilic hypervalent triorganodifluorostannate anions, which act as
fluorinating agents in the organic phase. © 2002 Elsevier Science Ltd. All rights reserved.
Many pharmaceuticals and plant protection agents con-
tain fluorinated substituents,1 thus methods for intro-
duction of this halogen into organic molecules are of
great interest.2,3 An important way to achieve this goal
is nucleophilic substitution of halogen or other nucleo-
fugal groups with F− anions.2–4 This reaction, although
widely used, encounters serious problems connected
with the insolubility of KF, the common F− source, in
the majority of solvents and also the high basicity of F−
anions, and so b-elimination is often a significant side
These problems can be solved by the use of cocatalysts:
tetravalent tin compounds such as R3SnF for PTC
fluorination of alkyl halides. It is known that Bu4N+F−
reacts with Ph3SnF giving a stable, crystalline salt,
Bu4N+Ph3SnF2 with a hypervalent pentacoordinated
−
anion.7 This compound can be used as a source of F−
anions in some reactions including fluorination of
haloalkanes.8 However, the high price and high molecu-
lar weight (630.5) preclude the use of this compound in
practical synthesis. We have assumed that due to the
ability of R3SnF or R3SnCl to react with F− and
produce lipophilic hypervalent anions, they can act as
cocatalysts in the PTC fluorination of haloalkanes as
shown in Scheme 1.
process. Phase-transfer catalysis, PTC,
a general
methodology for reactions using inorganic anions,5 is of
limited use for reactions of F− anions. Due to their low
lipophilicity and high energy of hydration, the ion-
exchange equilibrium governing PTC processes, is very
unfavorable for transfer of F− into the organic phase
and only liquid–solid systems can be used for such
reactions. The high basicity of F− often results in the
decomposition of tetraalkyl ammonium cations of the
PT catalyst.6
Indeed, triphenyltin fluoride and triphenyltin chloride
(the chloride, converted under the reaction conditions
into fluoride, is less expensive) both exhibit substantial
cocatalytic action on the PTC fluorination of the model
benzyl bromide, as is shown in experiments carried out
Scheme 1.
Keywords: fluorination; phase-transfer catalysis; tin compounds.
* Corresponding author. Fax: (+48 22) 632 66 81; e-mail: icho-s@icho.edu.pl
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00376-3

2762
M. Ma˛kosza, R. Bujok / Tetrahedron Letters 43 (2002) 2761–2763
under arbitrarily chosen conditions assuring moderate
conversions so that the effectiveness of various system
can be compared (Scheme 2).
lyzed with Ph3SnF gave mostly the expected sec-alkyl
fluorides (Scheme 3).
The cocatalytic action of R3SnF embraces two major
steps: formation of the complex anion and its further
reaction with alkylating agents, thus the effects of
different R groups on both of these steps should affect
the observed cocatalytic activity of R3SnF. The activity
The process can proceed as a direct reaction of the
haloalkanes with the complexed anion, Scheme 1b or
via dissociation of the latter and subsequent reaction of
the free F− anions, Scheme 1c, d, which albeit in low
concentration exhibit high activity. Although the ther-
of R3SnF2 as an F− donor should be higher for
−
mal stability of Bu4N+Ph3SnF2 (mp 192–193°) and its
electron donating substituents, they should, however,
deactivate R3SnF as a Lewis acid in the reaction with
−
119Sn and 19F NMR spectra, in which signals of tetra-
coordinated Sn and free F− anions are absent, suggest
that dissociation does not occur, we have answered this
question independently taking into account differences
−
KF giving R3SnF2 . Values of the relative rate con-
stants of the reaction of PhCH2Br with Bu4N+R3SnF2
−
prepared separately are given in Scheme 4 and confirm
in the reactivity patterns of F− and Ph3SnF2 anions.
the expected effect of R on the reactivity of R3SnF2 .
−
−
The reactions of sec-alkyl halides, mesylates or tosy-
lates with the highly basic F− anions proceed to a
substantial extent as b-elimination reactions, whereas
this undesired process should be less pronounced in the
Direct measurement of the rate of formation of
R3SnF2 as a function of R in R3SnF in the heteroge-
−
neous reaction with solid KF cannot give reliable data.
The observation that the cocatalytic activities of vari-
ous R3SnF under identical arbitrarily chosen conditions
do not parallel the activities of the corresponding
−
reactions of the much less basic Ph3SnF2 anions.
Indeed the data in Scheme 3 indicate that the typical
fluorination of 2-octyl tosylate and 1-(p-nitro-
phenyl)ethyl bromide with F− anions is accompanied by
substantial b-elimination, whereas the reaction cocata-
−
R3SnF2 in the reaction with PhCH2Br indicates that
the overall cocatalytic effectiveness is a superposition of
opposite effects.
Scheme 2.
Scheme 3. (a) Conditions as described for a typical experiment.10
Scheme 4.

M. Ma˛kosza, R. Bujok / Tetrahedron Letters 43 (2002) 2761–2763
4th ed., 1999; Vol. E 10a, pp. 548–596.
2763
The cocatalysis in PTC fluorination of alkyl halides and
sulfonates is of general application, but it is particularly
efficient, when, in the reaction with conventional fluori-
nating agents, b-elimination is a problem.
5. (a) Dehmlow, E. V.; Dehmlow, S. S. Phase-Transfer
Catalysis, 3rd ed.; Verlag Chemie: Weinheim, 1993; (b)
Starks, C. M., Liotta, C. L., Halpern, M. Phase-Transfer
Catalysis: Fundamental Applications and Industrial
Perspectives; Chapman & Hall: New York, 1994; (c)
Ma˛kosza, M.; Fedoryn´ski, M. Adv. Catal. 1987, 35, 375.
6. Sasson, Y.; Mushkin, N.; Alsu, E.; Negussie, S.; Der-
meik, S.; Zoran, A. In Phase-Transfer Catalysis, ACS
Symposium Series 659; Halpern, M., Ed.; Am. Chem.
Soc.: Washington, 1996; pp. 148–161.
In preparative (but without optimization) experiments,
high conversions and good yields of fluoroalkanes are
obtained; for instance PhCH2Fꢀ100% GLC (72% iso-
lated); PhCOCH2F-94% GLC, (64% isolated); 4-
O2NPhCHFCH3-84% GLC (80% isolated).10
7. Gingras, M. Tetrahedron Lett. 1991, 32, 7381–7384.
8. (a) Martinez, A. G.; Barcina, J. O.; del Rosario Colorado
Heras, M.; de Fresno Cereso, A. Org. Lett. 2000, 2,
1377–1378; (b) Kerverdo, S.; Fernandez, X.; Poulain, S.;
Gingras, M. Tetrahedron Lett. 2000, 41, 5841–5845.
9. Cox, D. P.; Terpin´ski, J.; Ławrynowicz, W. J. Org. Chem.
1984, 49, 3216–3219.
Acknowledgements
This work was generously supported by Bayer AG,
Germany. We thank the Foundation for Polish Science
for Professorial Subsydium and Professor W. Dmowski
for helpful discussion.
10. Freshly dried KF (8.78 g, 0.15 mol), Ph3SnF (1.11 g, 3
mmol), Bu4N+HSO4 (1.02 g, 3 mmol) and 1-(p-nitro-
−
phenyl)ethyl mesylate (7.38 g, 30 mmol) were stirred in
acetonitrile (21 ml) at 85°C for 10 h. The reaction mix-
ture was diluted with diethyl ether (35 ml) and treated
with water (120 ml). The precipitated catalyst was
removed, washed with ether (5×20 ml) and the ether
extract dried. The product 1-(p-nitrophenylethyl fluoride,
was purified by column chromatography. Yield 4.07 g
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