Tetrabutylammonium difluorotriphenylstannate [Bu4N][Ph 3SnF2]: Delivering carbon or fluorine ligands via hypercoordination

Article abstract of DOI:10.1055/s-2005-921747

The reagent, tetrabutylammonium difluorotriphenylstannate, was easily prepared on a multigram scale (～100 g). Several of its applications are presented, either as a soluble, thermally stable and anhydrous nucleophilic fluorinating agent or as a synthetic equivalent to PhMgX or PhLi species under aqueous and aerobic conditions. The proposed methodologies emphasize the concept of hypercoordination and its usefulness for improving selectivity, reactivity and shelf-stability of reagents. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-921747

182
PRACTICAL SYNTHETIC PROCEDURES
Tetrabutylammonium Difluorotriphenylstannate [Bu4N][Ph3SnF2]:
Delivering Carbon or Fluorine Ligands via Hypercoordination
Tetrabutylammonium
a
D
ifluorotrip
r
henylsta
c
nnate Gingras,* Yoann M. Chabre, J.-M. Raimundo
Chemical Laboratory of Organic and Metallic Materials, Faculty of Sciences,
University of Nice-Sophia Antipolis, 28 Av. Valrose, 06108 Nice Cedex 2, France
Fax +33(4)92076578; E-mail: gingras@unice.fr
PSP
Received 17 May 2005; revised 19 August 2005
No61
Abstract: The reagent, tetrabutylammonium difluorotriphenylstannate, was easily prepared on a multigram scale (~100 g). Several of its
applications are presented, either as a soluble, thermally stable and anhydrous nucleophilic fluorinating agent or as a synthetic equivalent
to PhMgX or PhLi species under aqueous and aerobic conditions. The proposed methodologies emphasize the concept of hypercoordination
and its usefulness for improving selectivity, reactivity and shelf-stability of reagents.
Key words: fluorination, tin, carbanions, sulfur, hypercoordination
Procedure 1
F
KF⋅2H2O
TBAF⋅3H2O
Ph
Ph
Ph3SnCl
1
Ph3SnF
Ph Sn
F
n-Bu4N
EtOAc, H2O
20 °C, 30 min
CH2Cl2
20 °C, 30 min
2
3 (66% overall)
Procedure 2
O
OSiMe3
Br
3, THF
+
–78 °C, 15 min
20 °C, 6 h
4
5
6 (99%)
Scheme 1
In 1991, one of us described the first hypercoordinated or- and importance. This reagent has found its way in the fine
ganotin 3 acting as an anhydrous nucleophilic fluorinating chemicals industry under the name ‘Gingras Reagent’, but
agent.1 Among many advantages, its thermal stability, its its cost discouraged an extensive use. The purpose of this
solubility in less polar solvents and its anhydrous nature article is threefold: a) to describe a reliable and multigram
(even after many years), led to a synthetic equivalent to preparative procedure of the reagent (~100 g), which was
tetrabutylammonium fluoride (TBAF) with improved checked several times,4 b) to report a detailed character-
properties. For instance, it was shown that drying TBAF ization and analysis of purity of 3 and c) to demonstrate
was almost impossible and gradually lead to its decompo- two classes of synthetic applications such as enol silyl
sition.2 More importantly, the concept of hypercoordina- ether C-alkylations and selective sulfurations of organo-
tion for modulating the properties of a reagent was put tins.
forward. Recently, this demonstration went further when
hypercoordination helped in stabilizing carbanionic spe-
cies for making synthetic equivalents to PhMgX or to Ph-
Li, albeit without their disadvantages (such as titration,
Procedures
strict anhydrous and inert conditions, pyrophoric or flam- Procedure 1 depicts for the first time a large-scale prepa-
mable properties).3
ration of triphenyltin fluoride 2 and its conversion to
tetrabutylammonium difluorotriphenylstannate (3)
Due to the usefulness of this ambivalent reagent, either as
synthetic equivalents to TBAF or to PhMgX/PhLi species
under aqueous and aerobic conditions, a plethora of pub-
lications followed, which clearly indicated its usefulness
(Scheme 1). In the first step, commercial triphenyltin
chloride (1) dissolved in ethyl acetate was rapidly con-
verted into polymeric triphenyltin fluoride 2 within min-
utes at 20 °C after addition of an aqueous solution of
potassium fluoride. Ethyl acetate played a major role to
ensure an almost complete precipitation of 2 as a white
powder, which was further rinsed with water. A trituration
with diethyl ether and filtration helped to remove the bulk
SYNTHESIS 2006, No. 1, pp 0182–0185
0
6
.
0
1
.2
0
0
6
Advanced online publication: 16.12.2005
DOI: 10.1055/s-2005-921747; Art ID: Z09605SS
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Tetrabutylammonium Difluorotriphenylstannate
183
of water. The crude product was dried under vacuum at agents for making Ar–S bonds, under aqueous and aerobic
about 50 °C until constant weight and was used as such in conditions (Scheme 3). It emphasized the versatile use of
the next step. Triphenyltin fluoride (2) quickly reacted at reagent 3 or hypercoordinated organotin fluoride species,
20 °C with commercial tetrabutylammonium fluoride tri- generated in situ, to transfer either a fluorine or a carbon
hydrate in dichloromethane. After two recrystallizations, ligand. It was a clear demonstration of the usefulness of
the expected product 3 was obtained. Practical aspects of hypercoordination to drive the control of selectivity and
those procedures were a quick reactivity at 20 °C (within reactivity. More importantly, previous sulfurations of or-
minutes) for both steps and simple precipitations or re- ganotins with elemental sulfur provided a mixture of sul-
crystallizations. Finally, it was shown that 100 g of pure furated products and organotin sulfides at higher
product was easily obtained without chromatography or temperatures near 200 °C.3 In our case, selective disulfide
special purification techniques. This reagent could be kept formation was observed with most sulfur transfer agents
for years without protection from moisture. The overall in the presence of water and air at 150 °C and within a few
yield of sufficiently pure product (92.6 g, 66%) represents minutes only. The presence of fluorine ligands was thus
an improvement over the first report (53%).1 A detailed crucial for selectivity and reactivity.
multigram preparative procedure of 3 has never been pre-
viously disclosed.
Procedure 2 presents a selective C-alkylation of enol silyl
ether 4, probably through a nucleophilic enol stannate
generated via a fluoride ion ligand exchange from Sn to Si
atoms1 (Scheme 1). An interesting feature was again a
prompt reactivity at 20 °C and selectivity for a mono C-
alkylation of cyclopentanone; the latter compound being
known to often generate polyalkylated products. It is note-
worthy that no O-alkylation reaction was observed. The
simplicity of the procedure was demonstrated when re-
agent 3 was added in one portion to a solution of enol silyl
ether 4 and benzyl bromide (5) in THF at low temperature.
The mixture was immediately warmed at 20 °C for a few
hours and an almost quantitative yield of benzylated prod-
uct 6 was obtained, after removing organotin by-products
over silica gel column by chromatography.
Scheme 3
Sulfuration of reagent 3 is an example of a somewhat
broad method that could be applied to a wide variety of or-
ganotins, even though the procedure was more efficient
with aryltins, compared to alkyltins. In short, optimization
of the process indicated that 10% of water in DMF in-
creased the selectivity for disulfide formation, the relative
molar ratio sulfur/organotin was best at 3.1. Coordinating
solvents such as DMF, DMSO, MeCN and 1,3-dimethyl-
2-imidazolidinone (DMI) were chosen, but DMF gave
overall the best results. A convenient compromise be-
tween temperature and reaction time was found at 150 °C
within 25 minutes for triphenyltin chloride. Electron rich
aryltins reacted faster than electron-poor aryltins. Finally,
it was observed that tetraaryltins and triaryltins reacted
faster than mono- and diaryltins. Some examples are de-
scribed in Scheme 3.
Applications
Reagent 3 has found several uses in synthesis such as: a)
nucleophilic fluorinations for making alkyl fluorides1,5
and gem-difluoroalkanes,6 b) trifluoromethylations,7,8a c)
difluoroalkylations,9 d) Stille couplings,10 e) enol silyl
ether alkylations1,8 and f) Ar–S bond formations.11
As shown in Procedure 2 (Scheme 1), enol silyl ethers
were activated with reagent 3 and then C-alkylated, possi-
bly through organotin enolates (experimentally unveri-
fied). Some examples of this reaction are shown in
Scheme 2.
1H and 13C and 19F NMR spectra were recorded in CDCl3 (refer-
enced to TMS or PhCF3) with Bruker instruments AC 200 (200
MHz) and AC 500 (500 MHz). FT-IR spectra were recorded with a
Perkin-Elmer 883 or Perkin-Elmer Spectrum 1000 instrument with
dry KBr disks (about 1% w/w of sample). Melting points (uncor-
rected) were determined in an open capillary with an Electrothermal
SMP3 (0.2 °C/min) apparatus. MS (EI, 70 eV) were recorded on a
Kratos MS-80RFA (University of Wisconsin-Madison, USA).
Not only fluoride ion ligand could be delivered from re-
agent 3, but a ‘nucleophilic’ phenyl ligand (or a Sn–C
bond) reacted with elemental sulfur or sulfur-transfer re-
OSiMe3
O
3 (1.1 equiv), THF
Triphenyltin Fluoride (2)
+
R
Br
R
To a 3-L, three-necked flask, fitted with a mechanical stirrer, was
added Ph3SnCl (1; 101.2 g, 0.263 mol, an inert atmosphere was not
needed). EtOAc (500 mL, laboratory grade) was poured into the
flask to dissolve the Ph3SnCl. An aqueous solution of KF·2H2O
(37.1 g, 0.394 mol) was prepared in warm distilled H2O (50 mL).
This solution was slowly poured into the main flask within a few
min and the mixture was mechanically stirred at 20 °C. Insoluble
–78 °C, 15 min
20 °C, 3.5–6 h
(1.2–1.5 equiv)
4
6
R = Ph (99%)
R = MeO2C (93%)
R = PhCH=CH (71%)
Scheme 2
Synthesis 2006, No. 1, 182–185 © Thieme Stuttgart · New York

184
M. Gingras et al.
PRACTICAL SYNTHETIC PROCEDURES
polymeric Ph3SnF (2) instantly precipitated. After stirring for 1 h
(less time might be needed), the mixture was filtered using a 1000-
mL fritted funnel. The resulting solid was washed with EtOAc (150
mL), distilled H2O (300 mL) and Et2O (100 mL, laboratory grade).
The product was partially dried in open air and was further dried un-
der vacuum until a constant weight (50 °C/0.1 mmHg). A white
powder was obtained (97.0 g, 99%) and used without any further
purification in the next step.
Anal. Calcd for C34H51F2NSn (630.48): C, 64.77; H, 8.15. Found: C,
64.92; H, 8.11.
Enol Silyl Ether Alkylations; 2-Benzylcyclopentanone (6);
Typical Procedure
Freshly distilled 1-(trimethylsilyloxy)cyclopentene (4; 1.41 mmol)
was added via a syringe to a solution of pure distilled benzyl bro-
mide (5, 2.12 mmol) in anhyd (dried over Na/benzophenone) THF
(5.0 mL). After cooling to –78 °C for 15 min, reagent 3 (1.55 mmol)
was added in one portion with the help of a lateral Gooch tube (cool-
ing might not be needed in some cases). The cooling bath was re-
moved whereupon the solid dissolved at 20 °C. Stirring was
continued for 6 h and a filtration over a short column of silica gel
(CH2Cl2) removed most of the organotins and salts. After evapora-
tion of solvents and drying under vacuum (0.1 mm Hg) overnight,
crude product 6 was obtained (293 mg, theory: 243 mg). A flash
chromatography over silica gel (acetone–hexane, 1:10) afforded
pure 6 (243 mg, 99%).
1H NMR (200 MHz, CDCl3): d = 7.40–7.10 (m, 5 H), 3.17 (dd,
J = 3.9, 13.6 Hz, 1 H), 2.52 (dd, J = 13.6, 9.5 Hz, 1 H), 2.48–2.25
(m, 2 H), 2.25–1.88 (m, 3 H), 1.88–1.45 (m, 2 H).
13C NMR (67.92 MHz, CDCl3): d = 219.76, 139.79, 128.68, 128.20,
125.94, 50.78, 37.96, 35.38, 28.92, 20.34
Tetrabutylammonium Difluorotriphenylstannate (3)
To a 3-L, three-necked flask, fitted with a mechanical stirrer, was
added the above prepared Ph3SnF (2; 82.4 g, 0.223 mol, an inert at-
mosphere was not needed). n-Bu4NF·3H2O (70.4 g, 0.223 mol, hy-
groscopic) was added in one portion to the flask, followed by
CH2Cl2 (250 mL, laboratory grade). More CH2Cl2 (50 mL) was
used to rinse the glassware. The mixture was mechanically stirred
at 20 °C for 35 min. The solids partly dissolved after 5 min but a fine
precipitate remained. Anhyd Na2SO4 (20 g) was then added in order
to remove some residual H2O and stirring was continued for about
10 min. The mixture was filtered through a 1000 mL fritted funnel
and the filtrate was collected in a 3-L Erlenmeyer flask. CH2Cl2 (50
mL) was used to wash the residual solid. To the combined filtrates,
was slowly added Et2O from a dropping funnel. After adding about
700 mL of Et2O, the first crystals appeared. More Et2O (300 mL)
was continuously added within 10 min while stirring with a stirring
bar. The flask was placed in a fridge at –20 °C (or at 0–3 °C in an
ice-bath) for about 1 h and the crystals were collected in a 1000-mL
HRMS (EI): m/z calcd for : 174.1052; found: 174.1045 [M+].
fritted funnel. The solid was washed further with Et2O (300 mL) and Acknowledgment
dried in open air overnight (moist solid, 123.9 g). It was then vacu-
The authors acknowledge the French Ministry of Research and the
um-dried at 20 °C (0.1 mm Hg) until constant weight. The resulting
white solid (102.8 g, mp 181.3 0.5 °C) was not sufficiently pure
and was recrystallized from CH2Cl2 (150 mL) with slow addition of
Et2O (450 mL). The mixture was left in the cold at –20 °C for 1 h.
The solid formed was filtered and washed with Et2O (200 mL).
[Note: both the mother liquors from the above two filtrations were
combined, evaporated and the residue was recrystallized from a
mixture of acetone (60 mL) and Et2O (250 mL), followed by addi-
tion of EtOAc (100 mL), see below]. After vacuum drying, the re-
agent 3 was obtained as white crystals (93.0 g, 66%); mp 186.4
0.4 °C. This first crop obtained was recrystallized by dissolving it in
warm acetone (500 mL, laboratory grade), followed by filtration be-
fore adding n-hexane (750 mL, laboratory grade) via a dropping
funnel. Two phases appeared and Et2O (500 mL) was slowly poured
into the mixture. The crystals were formed at 20 °C. After collecting
and drying them (0.1 mmHg), pure tetrabutylammonium difluoro-
triphenylstannate (3) was obtained (76.6 g); mp 191.0 0.5 °C
(Lit.1 mp 189.5 0.5 °C). The solvents from the mother liquors
were evaporated and the residual solid was combined with the crop
obtained from the earlier mother liquors (see above). The residual
solids from the combined mother liquors were recrystallized as
above (100 mL acetone, 200 mL Et2O, 200 mL n-hexane). The crys-
tals formed were collected (21.7 g) and recrystallized to provide an
additional material (16.0 g); mp 184.0 0.5 °C. Even this last crop
was sufficiently pure for most purposes; overall yield: 92.6 g (66%).
University of Nice-Sophia Antipolis.
References
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(4) It was claimed that reagent 3 could be prepared in a crude
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1H NMR (500 MHz, CDCl3/TMS): d = 8.09 (d, J = 5.0 Hz, 6 H),
7.25 (m, 9 H), 2.46 (t, J = 7.0 Hz, 8 H), 1.07 (m, 16 H), 0.88 (t,
J = 7.0 Hz, 12 H).
(9) (a) Berber, H.; Brigaud, T.; Lefebvre, O.; Plantier-Royon,
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13C NMR (125.77 MHz, CDCl3/TMS): d = 13.99 (CH3), 19.74
(CH2), 23.88 (CH2), 58.05 (CH2N), 127.65 (CH), 128.07 (CH),
138.05 (CH).
19F NMR (282.2 MHz, CDCl3/PhCF3): d = –95.24 (s), Sn satellites
(d, J[119Sn,19F] = 1971 Hz, d, [117Sn,19F] = 1887 Hz).
119Sn NMR (111.82 MHz, CD2Cl2/Me4Snext): d = –342.4 (t,
J[119Sn,19F] = 1971 Hz).
Synthesis 2006, No. 1, 182–185 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Tetrabutylammonium Difluorotriphenylstannate
185
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Synthesis 2006, No. 1, 182–185 © Thieme Stuttgart · New York