Catalytic B(C6F5)3[rad]H2O-promoted defluorinative functionalization of tertiary aliphatic fluorides

Article abstract of DOI:10.1016/j.jfluchem.2016.11.005

A B(C₆F₅)₃[rad]H₂O-catalyzed defluorinative functionalization of tertiary aliphatic fluorides is described that proceeds under benign reaction conditions. The synthetic utility of the method is exemplified throu

Full text of DOI:10.1016/j.jfluchem.2016.11.005

Accepted Manuscript
Title: Catalytic B(C6F5)3<ce:glyph
name="rad"/>H2O-promoted defluorinative functionalization
of tertiary aliphatic fluorides
Author: Marian Dryzhakov Edward Richmond Guang Li
Joseph Moran
PII:
S0022-1139(16)30364-5
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2016.11.005
FLUOR 8892
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Revised date:
Accepted date:
5-10-2016
3-11-2016
4-11-2016
Please cite this article as: Marian Dryzhakov, Edward Richmond, Guang
Li, Joseph Moran, Catalytic B(C6F5)3H2O-promoted defluorinative
functionalization of tertiary aliphatic fluorides, Journal of Fluorine Chemistry
http://dx.doi.org/10.1016/j.jfluchem.2016.11.005
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Highlights


B(C6F5)3•H2O catalyzes cleavage of C(sp3)–F bonds in tertiary aliphatic fluorides.
Generation of heteroatom-substituted tertiary aliphatic products including: azides, (thio)ethers,
sulfonamides, and carbamates.

Reactivity is achieved at room temperature with low catalyst loading (1 mol%).

Catalytic B(C6F5)3•H2O-Promoted Defluorinative Functionalization
of Tertiary Aliphatic Fluorides
Marian Dryzhakov, Edward Richmond, Guang Li and Joseph Moran*
Université de Strasbourg, CNRS, ISIS UMR 7006, F-67000 Strasbourg, France
*E-mail: moran@unistra.fr
Graphical abstract
Abstract
A B(C6F5)3•H2O-catalyzed defluorinative functionalization of tertiary aliphatic fluorides is described that
proceeds under benign reaction conditions. The synthetic utility of the method is exemplified through the fast
and efficient formation of a range of products with newly installed C(sp3) –N, –S, –C and –O bonds. This study
illustrates the broad reactivity of otherwise inert starting materials and provides a route to valuable and
synthetically underrepresented products that have not been accessed previously from such fluorinated
precursors.
Keywords
Aliphatic fluoride, Brønsted acid, catalysis, carbocation, alkyl azide, thioether
Highlights


B(C6F5)3•H2O catalyzes cleavage of C(sp3)–F bonds in tertiary aliphatic fluorides.
Generation of heteroatom-substituted tertiary aliphatic products including: azides, (thio)ethers,
sulfonamides, and carbamates.

Reactivity is achieved at room temperature with low catalyst loading (1 mol%).
1. Introduction
The unique properties of organic molecules that bear fluorine atoms in their structures have long been
appreciated by researchers in the fields of synthetic chemistry, medicine and material science [1]. This is
primarily due to the impact of the strong and highly polar C–F bond on the stability, as well as lipophilicity, of
such organofluorides [2]. However, the great demand for fluorinated materials has also generated significant
concern regarding their high resistance to decomposition and consequently their accumulation in the
environment [3]. With fluorine forming the strongest and a notably short (rW = 1.47 Å) single bond to carbon
[4], the fluoride ion is traditionally considered a poor leaving group [5], thus explaining the chemical inertness
of fluorinated substrates and the sluggishness of their environmental degradation. Although a number of
methods have been developed to break C(sp2)–F bonds in mono- and polyfluorinated aromatics [6], as well as
benzylic and allylic fluorides [7], the efficient cleavage of unactivated C(sp3)–F bonds in simple aliphatic
substrates remains underdeveloped [8]. Such transformations typically rely on the use of stoichiometric
fluorophilic main group Lewis acids or the use of a Lewis acidic catalyst accompanied by stoichiometric
fluoride-trapping silicon reagents (Figure 1 – Top) [9]. Thus, in addition to the high kinetic barrier for
functionalization of unactivated C(sp3)–F bonds, competitive elimination processes from the intermediate
carbocation often decrease the efficiency of target transformations [10].

Our research group has recently engaged in efforts toward the generation and utilization of aliphatic
carbocations from the corresponding alcohol precursors; transformations that can be catalyzed by the strong
Brønsted acid tris(pentafluorophenyl)borane hydrate (B(C6F5)3•H2O) [11]. Using this commercially available
catalyst, we subsequently disclosed the first catalytic [12] Friedel-Crafts reaction of tertiary aliphatic fluorides
with activated (hetero)arenes [13], a transformation that previously required the use of stoichiometric
fluorophilic reagents [14]. Herein we disclose the extension of this concept to the direct catalytic substitution
of tertiary aliphatic fluorides with a range of heteroatomic nucleophiles, under benign reaction conditions that
do not require stoichiometric activation (Figure 1 – Bottom).
Figure 1: Previous studies towards the catalytic substitution of tertiary aliphatic fluorides (top) and this work;
the practical, catalytic substitution of tertiary aliphatic fluorides with a variety of nucleophile classes (bottom).
2. Results and discussion
As an entry point to the heteroatomic substitution of tertiary aliphatic fluorides, we elected to focus on the
preparation of organic azides employing trimethylsilyl azide (TMSN3) as a functionalization agent. As well as
being a potent nucleophile, we reasoned that the trimethylsilyl group would have the added benefit of acting
as a fluoride trap in this transformation, thus favoring the accompanied formation of the target azide product.
Catalytic methods to produce alkyl azides remain scarce [11b] and to the best of our knowledge, a single study
on the catalytic azidation of tertiary alkyl fluorides using TMSN3 has been documented [9e], with the exception
of a study specific to adamantyl fluoride [9c]. In all of three reported reactions, a minimum of 10 mol% of
pyrophoric trialkylaluminium catalyst was used at cryogenic temperatures to provide alkyl azides, typically in
less than 65% isolated yield, presumably due to competitive side reactions. With this in mind, we were
delighted when our initial investigations into this reaction revealed that as little as 1 mol% of B(C6F5)3•H2O in
nitromethane is enough to obtain synthetically useful yields of aliphatic azide products at room temperature
(Table 1). Thus, homobenzylic tertiary aliphatic azides (2a-c) could be conveniently obtained after only 2 hours
of reaction time, followed by a simple chromatographic purification. Elimination-prone substrates could also
be employed, furnishing the desired products in good yield (2d). Conformationally restricted and cyclic
aliphatic azides (2e and 2f, respectively) were also smoothly prepared according to the optimized conditions.
Additionally, more complex structures, such as bisabolol-derived azide product (2g), are facile to obtain
without noticeable competitive azidation or isomerization of acid-sensitive double bonds [15].
Table 1 Scope of defluorinative azidation reaction.a,b

a Reagents and conditions: 1 (0.25 mmol), TMS-N3 (0.50 mmol), MeNO2 (0.125 mL), and B(C6F5)3•H2O (1 mol%).
Reaction stirred at r.t. for 1 h. b Isolated yields after column chromatography.
Thioethers, the prototypical sulfur(II) compounds which have versatile applications in synthetic, biological and
medicinal chemistry [16], are another class of substrates that could conceivably be accessed through the
interception of tertiary carbocations. Surprisingly, despite the utility of such substrates, synthetic methods to
access tertiary thioethers appear to be rather limited compared to other substitution patterns [17].
Additionally, to the best of our knowledge, to date there are no reports that describe the catalytic preparation
of such compounds from the corresponding fluorinated precursors [18]. Applying our standard reaction
conditions to the substitution of tertiary aliphatic fluorides with a variety of thiol nucleophiles yielded an array
of tertiary aliphatic thioethers (Table 2). Typically, high yields of substitution products were obtained most
probably as a result of the higher nucleophilicity of such S-centered nucleophiles. Arene-bearing (3a-d), as well
as cyclic (3e, 3g) and fully saturated (3f) thioethers could be easily synthesized. In addition to thiophenol (3a-f),
p-methoxyphenyl (PMP) thiol (3g) proved a competent nucleophile in this reaction.
Table 2 Scope of defluorinative thioether formation.a, b
a Reagents and conditions: 1 (0.25 mmol), RSH (0.50 mmol), MeNO2 (0.125 mL), and B(C6F5)3•H2O (1 mol%).
Reaction stirred at r.t. for 1 h. b Isolated yields after column chromatography.

As a further demonstration of the B(C6F5)3•H2O-initiated functionalization of fluorinated substrates, we next
sought to employ increasingly weaker nucleophiles. Surprisingly, to the best of our knowledge, little to no
literature evidence exists for the substitution of tertiary alkyl fluorides to produce heteroatom-substituted
products, such as alkyl ethers, carbamates and sulfonamides [19]. To this end, a series of O-, N- and C-centered
nucleophiles were tested in this reaction manifold under our otherwise identical reaction conditions (Table 3).
Thus, substitution of 1-fluoroadamantane with a variety of nucleophiles furnished a suite of adamantanes
bearing synthetically useful functional groups (4a-e). As would be expected, silylated nucleophiles such as silyl
enol ethers (4d) and allyltrimethylsilane (4g) proved competent reaction partners in this catalytic
transformation. Oxygen-bearing nucleophiles were also well tolerated providing the corresponding ethers (4a
and 4h) in moderate to excellent yields. Additionally, it was also possible to employ benzyl carbamate as a
nucleophile in such transformations, although the corresponding acid-labile products (4f and 4i) were isolated
in slightly diminished yield.
Table 3 Scope of defluorinative substitution with various nucleophiles.a, b
a Reagents and conditions: 1 (0.25 mmol), NuH or TMSNu (0.50 mmol), MeNO2 (0.125 mL), and B(C6F5)3•H2O (1
b
mol%). Reaction stirred at r.t. for 1 h. Isolated yields after column chromatography. c Reaction stirred at 50 °C
for 1 h.
Our previous kinetic study on the closely related Friedel-Crafts reaction of tertiary aliphatic fluorides initiated
by substoichiometric B(C6F5)3•H2O, revealed an autocatalytic reaction profile characterized by a short
induction period at room temperature followed by rapid product formation once the induction period has
expired [13]. Such an observation is consistent with the stoichiometric HF-byproduct being involved in the
formation of a superior HF-derived Brønsted acid catalysts in solution [20]. In accordance with this knowledge,
we suggest that the reactions described herein employing non-silylated nucleophiles also proceed by a similar
B(C6F5)3•H2O-initiated autocatalytic pathway. However, in cases where silylated nucleophiles are employed,
such as TMS-N3 (Table 1), the reaction is not autocatalytic, as the fluoride anion is trapped by silicon. Thus,
activation of the tertiary aliphatic fluoride by B(C6F5)3•H2O initiates heterolytic cleavage to generate the
tertiary aliphatic carbocation which is intercepted by the silylated nucleophile. Concomitantly, the liberated
fluoride is scavenged by the silyl group giving the TMS-F byproduct and allowing the regenerated B(C6F5)3•H2O
to re-enter the catalytic cycle (Figure 2). However, an alternative pathway involving activation of TMS-N3 by
the Brønsted acid with subsequent silylation-abstraction of fluoride by electrophilic silicon cannot be excluded.

Figure 2 Plausible catalytic cycles.
In conclusion, the catalytic defluorinative substitution of tertiary aliphatic fluorides with a variety of
nucleophiles has been described. Proceeding at ambient temperature and employing only 1 mol% of a
commercially available Brønsted acid catalyst, the generality of this simple and highly tractable methodology
has been exemplified through the preparation of a range of S-, O-, N-, and C-substituted products. To the best
of our knowledge, this is the first study where such functionalized products (thioethers, ethers, carbamates,
sulfonamides) have been accessed via simple catalytic substitution of a fluorinated tertiary C(sp3) center. In
other cases, for example azidation and alkylation reactions, prior routes have relied on the use of pyrophoric
activation reagents and cryogenic reaction conditions. The described methodology therefore provides an
immensely simplified and attractive variant to such substitution reactions with much practical appeal.

3. Experimental
3.1 General Information. All reagents and solvents were used as received without purification unless
otherwise stated. General laboratory techniques were used throughout, and no special precautions were
taken to exclude air or moisture from the reactions unless otherwise stated. Elevated temperatures were
achieved by way of a stirrer-hotplate, heating block and thermocouple. Where applicable, analytical thin layer
chromatography was performed on pre-coated aluminium plates (Kieselgel 60 F254 silica). TLC visualisation
was carried out with ultraviolet light (254 nm), followed by staining with a 1% aqueous KMnO4 solution. Flash
1
column chromatography was performed on Kieselgel 60 silica eluting with the solvent system stated. H, 13C
1
and 19F nuclear magnetic resonance (NMR) spectra were acquired on a Bruker Avance II 400 (400 MHz H, 100
MHz 13C, 376 MHz 19F) spectrometer at ambient temperature in the deuterated solvent stated. All chemical
shifts are quoted in parts per million (ppm) relative to the residual solvent as the internal standard. Data are
reported as: multiplicity (ap = apparent, br = broad, s = singlet, d = doublet, t = triplet, q = quartet, qn =
quintet, sx = sextet, sp = septet, oct = octet, non = nonet, m = multiplet), integration and coupling constant(s)
in Hz. Melting points were obtained on a Büchi Melting Point B-450 apparatus, and high resolution mass
spectra were obtained on an Agilent Technologies LCMS (ESI) or (EI) system.
3.2 Materials. Unless otherwise noted, all commercial materials were purchased from Sigma-Aldrich and
used without further purification. The substrates 3-bromo-3-methyl-1-phenylbutane [21], 3-chloro-3-methyl-1-
phenylbutane [21], 3-methoxy-3-methyl-1-phenylbutane [22], benzyl 1,1-dimethyl-3-phenylpropyl ether [11b],
1,1-dimethyl-3-phenylpropyl acetate [ 23 ] were prepared according to
a literature procedure.
Tris(pentafluorophenyl)borane B(C6F5)3 was purchased from Alfa Aesar and used under air, without any
precaution to exclude moisture or air. B(C6F5)3 is known to rapidly hydrate to B(C6F5)3H2O under these
conditions [24].
3.3 Preparation of Tertiary Aliphatic Fluorides
Aliphatic fluorides 1a-i were prepared as previously reported according to the general procedures outlined
below with identical spectral data [13].
General Procedure A To a solution of alcohol (9.75 mmol) in dry CH2Cl2 (30 mL) at -78 °C, was added
(diethylamino)sulfur trifluoride (2.60 mL, 3.14 g, 19.5 mmol, 2.00 equiv). The mixture was slowly warmed to
room temperature and stirred for 2 h. The reaction was diluted with CH2Cl2, washed with saturated aqueous
sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo (< 20 °C). The residue
was purified by silica gel chromatography (Petroleum ether) to afford the desired product.
3.4 Characterization Data for Novel Starting Materials
4-(2-Fluoro-6-methylhept-5-en-2-yl)-1-methylcyclohex-1-ene 1g
The title compound was prepared as an inconsequential, inseparable mixture of
diastereomers according to General Procedure A from (-)-α-bisabolol (1454 mg, 6.5 mmol). Isolated (1000 mg,
69%) as a colorless oil after column chromatography (Petroleum ether 100%). Rf = 0.3 (100% Petroleum ether).
Diastereomeric ratio [2.5:1]. 1H NMR (400 MHz, CDCl3)  5.42(1H, m), 5.17 (1H, ap. t, J = 7.0 Hz), 2.19-1.81 (9H,
m), 1.73 (3H, s), 1.70 (3H, s), 1.66 (3H, s), 1.39-1.27 (5H, m); 13C NMR (100 MHz, CDCl3)  133.8, 131.8, 124.2,
120.5, 98.5 (d, 1JCF = 168.7 Hz), 42.2 (d, 2JCF = 22.2 Hz), 37.3 (d, 2JCF = 22.2 Hz), 30.8, 26.1 (d, 3JCF = 6.1 Hz), 25.7,
3
2
23.9 (d, 3JCF = 7.3 Hz), 23.4, 22.0 (d, JCF = 4.6 Hz), 21.4 (d, JCF = 25.3 Hz); 19F NMR (376 MHz, CDCl3; CF3CO2H –
ext. std.)  -150.7 (m); HRMS (EI) for C15H25F [M+]: calcd. 224.1940; found 224.1934.
3.5 Defluorinative Substitution Reaction Procedure
General Procedure B To a 2 mL disposable vial containing the requisite aliphatic fluoride 1 (0.25 mmol, 1 equiv)
in nitromethane (0.125 mL, 2.0 M) was added the requisite nucleophile (0.50 mmol, 2 equiv), followed by
B(C6F5)3•H2O (1.3 mg, 2.5 µmol, 1.0 mol%). The vial was capped and the mixture allowed to stir for 1 h at room
temperature (23 °C), unless another temperature is specified in the procedure. At completion, the reaction

mixture was directly dry loaded onto silica and purified by column chromatography over silica according to the
conditions given. For reactions at elevated temperatures, an identical procedure was followed, however the
reaction was performed in a 10 mL screw-top vial. The desired temperature was achieved using a heating
block and contact thermometer.
3.6 Characterization Data for Substitution Products
(3-Azido-3-methylbutyl)benzene 2a
The title compound was prepared according to General Procedure B from fluoride 1a (42 mg,
0.25ꢀ mmol) and trimethylsilyl azide (0.066 mL, 0.50 mmol). Isolated (41 mg, 87%) as a colorless oil after
column chromatography over silica (Petroleum ether 95%, Et2O 5%). Rf = 0.39 (Petroleum ether 95%, Et2O 5%).
1H NMR (400 MHz, CDCl3)  7.37-7.24 (5H,m), 2.77-2.71 (2H, m), 1.88-1.83 (2H, m), 1.40 (s, 6H); 13C NMR (100
MHz, CDCl3)  141.9, 128.5, 128.3, 126.0, 61.5, 43.6, 30.8, 26.1. Analytical data are in accordance with the
literature [11b].
1-(3-Azido-3-methylbutyl)-4-chlorobenzene 2b
The title compound was prepared according to General Procedure B from fluoride 1b
(50 mg, 0.25 mmol) and trimethylsilyl azide (0.066 mL, 0.50 mmol). Isolated (48 mg, 86%) as a colorless oil
after column chromatography over silica (Petroleum ether 99.8%, Et2O 0.2%). Rf = 0.18 (Petroleum ether
1
99.8%, Et2O 0.2%). H NMR (400 MHz, CDCl3)  7.30 (2H, d, J = 8.4 Hz), 7.16 (2H, d, J = 8.3 Hz), 2.73-2.68 (2H,
m), 1.83-1.78 (2H, m), 1.39 (6H, s); 13C NMR (100 MHz, CDCl3)  140.3, 131.7, 129.7, 128.6, 61.3, 43.4, 30.1,
26.1. Analytical data are in accordance with the literature [11b].
1-(3-Azido-3-methylbutyl)-4-bromobenzene 2c
The title compound was prepared according to General Procedure B from fluoride 1c
(61 mg, 0.25 mmol) and trimethylsilyl azide (0.066 mL, 0.50 mmol). Isolated (56 mg, 84%) as a colorless oil
after column chromatography over silica (Petroleum ether 99.8%, Et2O 0.2%). Rf = 0.35 (Petroleum ether
1
99.8%, Et2O 0.2%). H NMR (400 MHz, CDCl3)  7.40 (2H, d, J = 8.2 Hz), 7.07 (2H, d, J = 8.2 Hz), 2.66-2.61 (2H,
m), 1.77-1.73 (2H, m), 1.33 (6H, s); 13C NMR (100 MHz, CDCl3)  140.8, 131.5, 130.1, 119.7, 61.3, 43.4, 30.2,
26.1. Analytical data are in accordance with the literature [11b].
(2-Azido-2-methylpropyl)benzene 2d
The title compound was prepared according to General Procedure B from fluoride 1d (38 mg,
0.25 mmol) and ꢀtrimethylsilyl azide (0.066 mL, 0.50 mmol). Isolated (33 mg, 74%) as a colorless oil after
column chromatography over silica (Petroleum ether 99%, Et2O 1%). Rf = 0.15 (Petroleum ether 99%, Et2O 1%).
1H NMR (400 MHz, CDCl3)  7.40-7.26 (5H, m), 2.83 (2H, s), 1.33 (6H, s); 13C NMR (100 MHz, CDCl3)  136.8,
130.5, 128.1, 126.8, 61.8, 47.6, 26.0. Analytical data are in accordance with the literature [11b].
1-Azidoadamantane 2e
The title compound was prepared according to General Procedure B from fluoride 1e (39 mg, 0.25
mmol) and trimethylsilyl azide (0.066 mL, 0.50ꢀ mmol). Isolated (34 mg, 77%) as aꢀ white solid after column
chromatography over silica (Petroleum ether 99.5%, Et2O 0.5%). Rf = 0.23 (Petroleum ether 99.5%, Et2O 0.5%).

1H NMR (400 MHz, CDCl3)  2.20 (3H, s), 1.84 (6H, app. d. J = 2.7 Hz), 1.71 (6H, q, J = 10.8 Hz); 13C NMR (100
MHz, CDCl3)  59.0, 41.5, 35.9, 29.8. Analytical data are accordance with the literature [11b].
1-Azido-1-butylcyclohexane 2f
The title compound was prepared according to General Procedure B from fluoride 1f (40 mg, 0.25
mmol) and trimethylsilyl azide (0.066 mL, 0.50ꢀ mmol). Isolated (40 mg, 89%) as a colorless liquid after column
1
chromatography over silica (Petroleum ether 100%). Rf = 0.38 (Petroleum ether 100%). H NMR (400 MHz,
CDCl3)  1.68-1.50 (10H, m), 1.39-1.22 (6H, m), 0.92 (3H, t, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3)  64.2, 40.0,
34.7, 25.6, 25.5, 23.2, 22.3, 14.1. Analytical data are in accordance with the literature [11b].
4-(2-Azido-6-methylhept-5-en-2-yl)-1-methylcyclohex-1-ene 2g
The title compound was prepared as an inseparable mixture of diastereomers according to
General Procedure B from fluoride 1g (56 ꢀmg, 0.25 mmol) and trimethylsilyl azide (0.066 mL, 0.50 mmol).
Isolated (42 mg, 68%) as colorless oil after column chromatography over silica (Petroleum ether 99.7%, Et2O
0.3%). Rf = 0.25 (Petroleum ether 99.7%, Et2O 0.3%). Diastereomeric ratio [1:1]. Due to the overlapping signals,
the NMR data is reported cumulatively for both diastereomers. 1H NMR (400 MHz, CDCl3)  5.39 (ap. d, 1H, J =
5.1 Hz), 5.12 (ap. t, 1H, J = 6.9 Hz), 2.08-2.00 (m, 5H), 1.89-1.78 (m, 2H), 1.71 (3H, s), 1.67 (3H, s), 1.64 (3H, s),
1.61-1.54 (2H, m), 1.36-1.22 (5H, m). Analytical data are accordance with the literature [11b].
(2-Methyl-4-phenylbutan-2-yl)(phenyl)sulfane 3a
The title compound was prepared according to General Procedure B from ꢀfluoride 1a (42 mg,
0.25 mmol) and thiophenol (0.052 mL, 0.50 ꢀmmol). Isolated (60 mg, 94%) as a white solid after column
1
chromatography over silica (Petroleum ether 99%, Et2O 1%). Rf = 0.20 (Petroleum ether 99%, Et2O 1%). H
NMR (400 MHz, CDCl3)  7.58 (2H, dd, J = 7.6, 1.4 Hz), 7.39-7.26 (5H, m), 7.22-7.19 (3H, m), 2.87-2.83 (m, 2H),
1.82-1.78 (m, 2H), 1.34 (s, 6H); 13C NMR (100 MHz, CDCl3)  142.5, 137.5, 132.3, 128.8, 128.6, 128.4, 128.4,
125.8, 49.2, 44.3, 31.4, 29.0. Analytical data are in accordance with the literature [25].
(4-(4-Chlorophenyl)-2-methylbutan-2-yl)(phenyl)sulfane 3b
The title compound was prepared according to General Procedure B from fluoride 1b
(50 mg, 0.25 mmol) and thiophenol (0.052 mL, 0.50 mmol). Isolated (67 mg, 92%) as a white solid after column
chromatography over silica (Petroleum ether 99%, Et2O 1%). Rf = 0.14 (Petroleum ether 99%, Et2O 1%). mp 45-
47 °C; 1H NMR (400 MHz, CDCl3)  7.59 (2H, d, J = 6.8 Hz), 7.44-7.37 (3H, m), 7.29 (2H, d, J = 8.2 Hz), 7.16 (2H,
d, J = 8.2 Hz), 2.87-2.83 (m, 2H), 1.80-1.76 (m, 2H), 1.36 (s, 6H); 13C NMR (100 MHz, CDCl3)  140.9, 137.5,
132.1, 131.5, 129.7, 128.8, 128.6, 128.5, 49.1, 44.1, 30.8, 29.0; HRMS (ESI) for [M+K] C17H1935ClSK found
329.0554, calcd. 329.0528 (-7.9 ppm).
(4-(4-Bromophenyl)-2-methylbutan-2-yl)(phenyl)sulfane 3c
The title compound was prepared according to General Procedure B from fluoride 1c
(61 mg, 0.25 mmol) and thiophenol (0.052 mL, 0.50 mmol). Isolated (72 mg, 87%) as a white solid after column
chromatography over silica (Petroleum ether 99%, Et2O 1%). Rf = 0.15 (Petroleum ether 99%, Et2O 1%). mp 49-

50 °C; 1H NMR (400 MHz, CDCl3)  7.56-7.54 (2H, m), 7.41-7.32 (5H, m), 7.07-7.05 (2H, m), 2.79 (2H, dt, J = 8.1,
4.3 Hz), 1.76-1.72 (2H, m), 1.32 (s, 6H); 13C NMR (100 MHz, CDCl3)  141.4, 137.5, 132.1, 131.5, 130.2, 128.8,
128.6, 119.5, 49.1, 44.0, 30.8, 29.0; HRMS (ESI) for [M+K] C17H1979BrSK found 373.0025, calcd. 373.0022 (-0.58
ppm).
(2-Methyl-1-phenylpropan-2-yl)(phenyl)sulfane 3d
The title compound was prepared according to General Procedure B from fluoride 1d (38 mg,
0.25 mmol) and thiophenolꢀ (0.052 mL, 0.50 mmol). Isolated (55 mg, 90%) as a colorless oil after column
1
chromatography over silica (Petroleum ether 99%, Et2O 1%). Rf = 0.13 (Petroleum ether 99%, Et2O 1%). H
NMR (400 MHz, CDCl3)  7.63 (2H, d, J = 6.4 Hz), 7.44-7.37 (3H, m), 7.35-7.28 (3H, m), 7.23-7.21 (2H, m), 2.95
(m, 2H), 1.26 (s, 6H); 13C NMR (100 MHz, CDCl3)  137.8, 137.7, 132.1, 130.8, 128.8, 128.6, 127.9, 126.4, 49.3,
49.0, 28.1; HRMS (ESI) for [M+K] C16H18SK found 281.0761, calcd. 281.0761 (+0.06 ppm).
1-Adamantanyl(phenyl)sulfane 3e
The title compound was prepared according to General Procedure B from fluoride 1e (39 mg, 0.25
mmol) and thiophenol (0.052 mL, 0.50 mmol). Isolated (57 mg,ꢀ 94%) as a white solid after column
1
chromatography over silica (Petroleum ether 99%, Et2Oꢀ 1%). Rf = 0.27 (Petroleum ether 99%, Et2O 1%). H
NMR (400 MHz, CDCl3)  7.52-7.48 (2H, m), 7.38-7.26 (3H, m), 2.01 (s, 3H), 1.84-1.80 (m, 6H), 1.66-1.58 (m,
6H); 13C NMR (100 MHz, CDCl3)  131.7, 130.6, 128.6, 128.3, 47.9, 43.6, 36.2, 30.0. Analytical data are in
accordance with the literature [13].
(2,6-Dimethylheptan-2-yl)(phenyl)sulfane 3f
The title compound was prepared according to General Procedure B from fluoride 1h
(40 mg, 0.25 mmol) and thiophenol (0.051 mL, 0.50 mmol). Isolated (50 mg, 85%) as a colorless liquid after
1
column chromatography over silica (100% Petroleum ether). Rf = 0.30 (100% Petroleum ether). H NMR (400
MHz, CDCl3)  7.52-7.50 (2H, m), 7.38-7.29 (3H, m), 1.59-1.51 (1H, m), 1.49-1.40 (4H, m), 1.23 (6H, s), 1.17-1.12
(2H, m), 0.90 (3H, s), 0.88 (3H, s); 13C NMR (100 MHz, CDCl3)  137.7, 132.6, 128.7, 128.5, 49.6, 42.8, 39.5, 28.9,
28.1, 22.8, 22.7. Analytical data are in accordance with the literature [26].
(1-Butylcyclohexyl)(4-methoxyphenyl)sulfane 3g
The title compound was prepared according to General Procedure B from fluoride 1f
(40 mg, 0.25 mmol) and 4-methoxythiophenol (0.061 mL, 0.50 mmol). Isolated (55 mg, 95%) as a colorless
liquid after column chromatography over silica (100% petroleum ether). Rf = 0.27 (Petroleum ether 99%, Et2O
1%). 1H NMR (400 MHz, CDCl3)  7.41-7.37 (2H, m), 6.86-6.82 (2H, m), 3.82 (3H, s), 1.79-1.76 (2H, m), 1.58-1.41
(8H, m), 1.36-1.27 (6H, m), 0.94 (3H, t, J = 7.3 Hz); 13C NMR (100 MHz, CDCl3)  160.2, 139.0, 122.9, 114.1, 55.4,
53.9, 38.7, 36.2, 26.2, 25.8, 23.3, 22.4, 14.4; HRMS (ESI) for [M+K] C17H26OSK calcd. 317.1336, found 317.1292.
1-Phenethoxyadamantane 4a
The title compound was prepared according to General Procedure B from fluoride 1e (39 mg,
0.25 mmol) and 2-phenylethanol (0.060 mL, 0.50 mmol), however the reaction was performed at 50 °C.
Isolated (59 mg, 92%) as a colorless oil after column chromatography over silica (95% Petroleum ether, 5%

1
EtOAc). Rf = 0.29 (Petroleum ether 97%, EtOAc 3%). H NMR (400 MHz, CDCl3)  7.30-7.18 (5H, m), 3.61 (2H, t,
J = 7.6 Hz), 2.83 (2H, t, J = 7.6 Hz), 2.13 (3H, br s), 1.74 (6H, ap. d, J = 2.8 Hz), 1.65-1.56 (6H, m); 13C NMR (100
MHz, CDCl3)  139.5, 129.1, 128.3, 126.2, 72.3, 61.4, 41.7, 37.7, 36.6, 30.6; HRMS (ESI) for [M+Na] C18H24ONa
found 279.1730, calcd. 279.1719 (-3.9 ppm).
N-(Adamantan-1-yl)-4-methylbenzenesulfonamide 4b
The title compound was prepared according to General Procedure B from fluoride 1e (39 mg, 0.25
mmol) and p-toluenesulfonamide (86 mg, 0.50 mmol). Isolated (72 mg, 95%) as a white solid after column
chromatography over silica (90% Petroleum ether, 10% EtOAc). Rf = 0.15 (Petroleum ether 90%, EtOAc 10%).
mp 167-168 °C; 1H NMR (400 MHz, CDCl3)  7.78 (2H, d, J = 8.4 Hz), 7.28-7.26 (2H, m), 4.44 (1H, br s), 2.42 (3H,
s), 2.01 (3H, br s), 1.79 (6H, d, J = 2.7 Hz), 1.62-1.54 (6H, m); 13C NMR (100 MHz, CDCl3)  142.8, 141.3, 129.5,
127.0, 55.1, 43.1, 36.0, 29.6, 21.6. Analytical data are in accordance with the literature [27].
1-Allyladamantane 4c
The title compound was prepared according to General Procedure B from fluoride 1e (39 mg, 0.25
mmol) and allyltrimethylsilane (0.057 mL, 0.50 mmol). Isolated (31 mg, 70%) as a colorless liquid after column
chromatography over silica (100% petroleum ether). As with previous literature preparations of the material,
1
the NMR spectra show traces of impurities [28]. Rf = 0.83 (Petroleum ether 100%). H NMR (400 MHz, CDCl3) 
5.84 (1H, ddtd, J = 16.9, 10.1, 7.5, 0.7 Hz), 5.03-4.94 (2H, m), 1.95 (3H, br s), 1.82 (1H, d, J = 7.5 Hz), 1.72-1.60
(6H, m), 1.49-1.47 (6H, m); 13C NMR (100 MHz, CDCl3)  135.1, 116.6, 49.2, 42.6, 37.3, 33.0, 28.8. Analytical
data are in accordance with the literature [28].
2-(Adamantan-1-yl)-1-phenylethanone 4d
The title compound was prepared according to General Procedure B from fluoride 1e (39 mg, 0.25
mmol) and 1-phenyl-1-trimethylsiloxyethylene (96 mg, 0.50 mmol). Isolated (60 mg, 94%) as a colorless oil
after column chromatography over silica (Petroleum ether 99%, Et2O 1%). Rf = 0.29 (Petroleum ether 100%). 1H
NMR (400 MHz, CDCl3)  7.97-7.94 (2H, m), 7.57-7.53 (1H, m), 7.48-7.43 (2H, m), 2.73 (2H, s), 1.95 (3H, br s),
1.71-1.61 (12H, m); 13C NMR (100 MHz, CDCl3)  200.4, 139.0, 132.8, 128.5, 128.5, 51.3, 43.1, 36.9, 34.1, 28.8.
Analytical data are in accordance with the literature [29].
2-(Adamantan-1-yl)-1,3-diphenylpropane-1,3-dione 4e
The title compound was prepared according to General Procedure B from fluoride 1e (39 mg,
0.25 mmol) and dibenzoylmethane (112 mg, 0.50 mmol). Isolated (70 mg, 78%) as a white solid after column
chromatography over silica (96% Petroleum ether, 4% EtOAc). Rf = 0.24 (Petroleum ether 95%, EtOAc 5%). mp
1
212-214 °C; H NMR (400 MHz, CDCl3)  8.01-7.98 (4H, m), 7.56-7.52 (2H, m), 7.47-7.43 (4H, m), 5.47 (1H, s),
1.97 (3H, br s), 1.88 (6H, ap. d. J = 2.8 Hz), 1.66 (6H, br s); 13C NMR (100 MHz, CDCl3)  194.3, 138.7, 133.1,
128.9, 128.5, 64.1, 41.2, 39.7, 36.8, 28.9. Analytical data are in accordance with the literature [30].
Benzyl (1-butylcyclohexyl)carbamate 4f

The title compound was prepared according to General Procedure B from fluoride 1f (40 mg,
0.25 mmol) and benzyl carbamate (76 mg, 0.50 mmol). Isolated (39 mg, 54%) as a pale yellow liquid after
column chromatography over silica (95% Petroleum ether, 5% EtOAc). Rf = 0.43 (Petroleum ether 95%, EtOAc
1
5%). H NMR (400 MHz, CDCl3)  7.37-7.31 (5H, m), 5.06 (2H, s), 4.50 (1H, br s), 1.97-1.92 (2H, m), 1.71-1.66
(2H, m), 1.58-1.15 (12H, m), 0.88 (3H, t, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3)  154.5, 137.1, 128.6, 128.1,
66.0, 55.0, 38.2, 35.1, 25.9, 25.4, 23.2, 21.8, 14.3; HRMS (ESI) for [M+K] C18H27NO2K found 328.1676, calcd.
328.1673 (-0.69 ppm).
4,4-Dimethyldodec-1-ene 4g
The title compound was prepared according to General Procedure B from fluoride 1i (44 mg, 0.25
mmol) and trimethylallylsilane (0.057 mL, 0.50 mmol). Isolated (22 mg, 43%) as a colourless liquid (>90%
1
purity) after column chromatography over silica (100% Petroleum ether). Rf = 0.90 (Petroleum ether 100%). H
NMR (400 MHz, CDCl3)  5.82 (1H, ddt, J = 16.7, 10.4, 7.4 Hz), 5.03-4.96 (2H, m), 1.94 (2H, dt, J = 7.5, 1.1 Hz),
1.31-1.17 (14H, m), 0.92-0.88 (3H, m), 0.87-0.85 (6H, m); 13C NMR (100 MHz, CDCl3)  136.2, 116.5, 46.6, 42.1,
33.2, 32.1, 30.8, 29.8, 29.5, 27.2, 24.1, 22.8, 14.3. Analytical data are in accordance with the literature [31].
1-Chloro-4-(3-methyl-3-(3-phenylpropoxy)butyl)benzene 4h
The title compound was prepared according to General Procedure B from fluoride 1b
(50 mg, 0.25 mmol) and 3-phenylpropan-1-ol (0.068 mL, 0.50 mmol). Isolated (46 mg, 58%) as a colorless oil
after column chromatography over silica (97% Petroleum ether, 3% EtOAc). Rf = 0.32 (Petroleum ether 97%,
1
EtOAc 3%). H NMR (400 MHz, CDCl3)  7.30-7.19 (7H, m), 7.08 (2H, d, J = 8.3 Hz), 3.36 (2H, t, J = 6.4 Hz), 2.71
(2H, t, J = 7.7 Hz), 2.64-2.59 (2H, m), 1.92-1.85 (2H, m), 1.75-1.70 (2H, m), 1.20 (6H, s); 13C NMR (100 MHz,
CDCl3)  142.3, 141.6, 131.4, 129.8, 128.6, 128.5, 128.4, 125.8, 74.1, 60.4, 42.5, 32.7, 32.2, 29.8, 25.7; HRMS
(ESI) for [M+Na] C20H2535ClONa found 339.1488, calcd. 339.1486 (-0.52 ppm).
Benzyl (4-(4-bromophenyl)-2-methylbutan-2-yl)carbamate 4i
The title compound was prepared according to General Procedure B from fluoride 1c
(61 mg, 0.25 mmol) and benzyl carbamate (76 mg, 0.50 mmol). Isolated (37 mg, 39%) as a colorless oil after
column chromatography over silica (95% Petroleum ether, 5% EtOAc). Rf = 0.21 (Petroleum ether 95%, EtOAc
1
5%). H NMR (400 MHz, CDCl3)  7.38-7.30 (7H, m), 7.02 (2H, d, J = 7.4 Hz), 5.06 (2H, s), 4.66 (1H, br s), 2.54-
2.50 (2H, m), 1.99-1.95 (2H, m), 1.34 (6H, s); 13C NMR (100 MHz, CDCl3)  154.5, 141.2, 136.7, 131.4, 130.2,
128.6, 128.1, 128.1, 119.4, 66.1, 52.8, 41.7, 30.2, 27.3; HRMS (ESI) for [M+K] C19H2279BrNO2K found 414.0446,
calcd. 414.0465 (+4.7 ppm).
4. Acknowledgements
This work was supported in part by a LabEx CSC “Chemistry of Complex Systems” grant and the Marie Curie
Actions FP7-PEOPLE Program (No. CIG-2012-326112). M.D. and E.R. thank the gion lsa e and the
Leverhulme Trust for fellowships, respectively.

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