Synthesis of quaternary α-perfluoroalkyl lactams via electrophilic perfluoroalkylation

Article abstract of DOI:10.1039/c6cc00700g

Efficient protocols enabling the rapid installation of trifluoromethyl, as well as further functionalized fluoroalkyl groups by an electrophilic perfluoroalkylation of lactam-derived ketene silyl amides (KSAs) using hypervalent iodine reagents 1 and 2 have been developed.

Full text of DOI:10.1039/c6cc00700g

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: D. Katayev, J.
Vaklavik, F. Brüning, B. Commare and A. Togni, Chem. Commun., 2016, DOI: 10.1039/C6CC00700G.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 4
View Article Online
DOI: 10.1039/C6CC00700G
ChemComm
COMMUNICATION
Synthesis of Quaternary α-Perfluoroalkyl Lactams via Electrophilic
Perfluoroalkylation†
D. Katayev,a J. Václavík,ab F. Brüning,a B. Commare,a and A. Togni*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
CN
O2N CO2R
CF3
Efficient protocols enabling the rapid installation of
trifluoromethyl, as well as further functionalized fluoroalkyl
groups by an electrophilic perfluoroalkylation of lactam-derived
ketene silyl amides (KSAs) using hypervalent iodine reagents 1 and
2 have been developed.
silyl ketene
imines
α-nitro
esters
Ar
R'
CF3
up to 93%
up to 99%
O
F3C
I
O
Rf
I
O
O
β-keto
esters
ketene silyl
acetals
O
or
CF3
R'''
R'
CF3
O
CO2R
n
up to 94%
O
R''
silyl enol
ethers
1
2
ketene silyl
amides
up to 95%
O
The selective introduction of
a single fluorine atom, a
PG
''This work''
Rf = CF3, C2F5, C2F4-R
CF3
R''
N
Rf
trifluoromethyl or perfluoroalkyl group into an organic
molecule is an important process for the development of new
materials,1 pharmaceuticals2 and crop protection chemicals,3
and has attracted much attention in recent years. The
presence of fluorine atoms for example in drugs can
potentially improve their biological activity as a consequence
of a number of parameters such as e.g. increased lipophilicity,
binding selectivity, or improved metabolic stability. α-
Fluoroalkylated cyclic amides are particularly important as
core structures present in bioactive compounds4 and as
precursors for the synthesis, for instance, of α-fluoroalkylated
amides5 and β-fluoroalkylated alkylamine derivatives.4c,6 It has
Ar
R'
up to 99%
R
n
up to 95%
Scheme
formation of a quaternary carbon center.
1
Application of hypervalent iodine(III)-Rf reagents
1
and 2 in the
visible-light photocatalysts8 or transition-metal catalysts.9
Alternatively, over the last decade, methods for electrophilic
trifluoromethylation, especially those using hypervalent iodine
reagents
1 and 2a (Rf = CF3), have found an extremely broad
application in organic synthesis.10 These reagents are easily
accessible from commercially available 2-iodobenzoic acid as
air-stable crystalline solids.11 However, only a few methods for
the construction of a quaternary carbon center using reagents
also
been
demonstrated
that
quaternary
α-
1
and 2a have been reported so far. As outlined in Scheme 1,
trifluoromethylated γ-lactams and their reduced form, β-
trifluoromethylated pyrrolidines, exhibit excellent insecticidal
efficacy and may be used as pesticides in agrochemistry or in
the field of veterinary medicine.6b Thus, the development of
substrates, such as α-CF3-α-nitro esters,12 α-CF3-β-keto
esters,11b,12b,12d,13 α-CF3-aryl ketones9a,12a,b,13 and α-CF3-
nitriles14 can be prepared via direct trifluoromethylation or
from the corresponding metal enolates or their equivalents
under mild reaction conditions in good to excellent yields.
Recently, our laboratory introduced an efficient protocol for
the trifluoromethylation of ketene silyl acetals employing
new synthetic methods to generate
a fluoroalkylated
quaternary carbon next to a carbonyl center has emerged as a
central objective in organofluorine chemistry. To this goal,
important advances have been recently achieved. These
include a series of fluoroalkylations of nucleophilic enolates or
enolate equivalents promoted and/or initiated by radical
initiators,7
reagents
1 and 2a, which proceeds under trimethylsilyl
triflimide catalysis (TMSNTf2, up to 2.5 mol %), providing direct
access to a variety of substituted α-trifluoromethyl esters and
lactones.15
Thus, based on these general considerations and inspired
by previously developed methods, we turned our attention to
lactams, an important class of compounds. However, first
attempts to directly trifluoromethylate in-situ generated
lithium enolate of lactam 3a using reagents
1 or 2a were
unsuccessful, leading to product formation only in trace
amounts with concomitant decomposition of the reagents.
This journal is © The Royal Society of Chemistry 20xx
Chem. Commun., 2016, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 4
View Article Online
DOI: 10.1039/C6CC00700G
COMMUNICATION
Journal Name
Table 1 Optimization of reaction conditions for the catalytic trifluoromethylation
of KSA 4a
O
OTMS
Bn
Me
1 or 2a
catalyst (x mol %)
Me
N
CF3
Bn
N
CH2Cl2, -78 °C to rt
19 h
4a
8a
N
O
N
O
N
O
N
O
M
V
tBu
tBu
Cl
O
tBu
tBu
5: M=Fe; 6: M=Mn
7
entrya
reagent
catalyst
mol %
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
1
-
-
-
-
1
1
1
1
1
2.5
3
1
42
67
79
68
62
71
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
Zn(NTf2)2
LiNTf2
AgNTf2
CuNTf2
TMSNTf2
TMSNTf2
TMSNTf2
[V(acac)2O]
5
96(94)c
86
83
74
74
91
93
Reaction conditions: a4a
–
l
(1.3 mmol, 1.3 M in DCM), 2a (1.0 mmol), TMSNTf2 (1
mol %), –78 °C to rt, 19 h. bOne-pot procedure: LDA (1.4 mmol), 3a
–l (1.3 mmol),
1
1
1
6
7
TMSCl (2.2 mmol), THF, –78 °C to rt, 19 h; 2a (1.0 mmol), TMSNTf2 (1 mol %), –78
°C to rt, 19 h. cIn the absence of TMSNTf2. dOne-pot procedure: LDA (2.8 mmol),
3k (1.3 mmol), TMSCl (4.4 mmol), THF, –78 °C to rt, 19 h; 2a (1.0 mmol), TMSNTf2
(1 mol %), –78 °C to rt, 19 h.
aReaction conditions: 4a (0.3 mmol, 0.5 M in CH2Cl2),
1 or 2a (0.23 mmol),
catalyst (1-3 mol %), Ar atmosphere, 19 h. bYields were determined by 19F NMR
using benzotrifluoride as an internal standard. cIsolated yield. TMS-trimethylsilyl.
Scheme
trifluoromethylation of carbonyl compounds: lactam scope.
2
α-Trifluoromethylation of KSAs and direct, one-pot α-
To overcome this problem, we envisaged that the conversion
of substrates to the corresponding ketene silyl amides (KSAs)
might be beneficial to control the reactivity of these species
towards hypervalent iodine-CF3 reagents. Hence, we report
herein a mild, operationally simple and highly efficient method
for the α-trifluoromethylation and α-perfluoroalkylation of
trifluoromethylation step.† As summarized in Scheme 2, a
broad range of KSAs exhibiting diverse steric and electronic
properties readily participate in this transformation. First
experiments showed that lactam-derived KSAs undergo
trifluoromethylation with reagent 2a even without the
TMSNTf2
trifluoromethylated products in moderate to good yields (8a
8e 8f 8g). We believe that the level of efficiency observed
catalyst
giving
the
corresponding
α-
lactam-derived KSAs by the use of reagents
1 and 2a in the
,
presence of catalytic amounts of TMSNTf2 (1 mol %) or even
under catalyst-free conditions. Additionally, we describe a
direct one-pot protocol enabling these transformations
without the isolation of intermediate KSAs.
,
,
under catalyst-free conditions is the result of both low steric
requirements of the substrates and their high electron density.
The addition of 1 mol % of the catalyst (TMSNTf2) considerably
improved the reactivity as shown in Scheme 2. The reaction
tolerates different N-protecting groups, albeit benzyl (Bn),
benzyloxymethyl (BOM), and tert-butyloxycarbonyl (Boc)
derivatives formed the corresponding products in lower yields
To probe the viability of this transformation, we
investigated the reaction between KSA 4a and reagents
2a under various conditions (Table 1). It turned out that the
direct trifluoromethylation of 4a using either or 2a in CH2Cl2
1 and
1
at low temperature (–78 °C) gave after 19 h the corresponding
product 8a in only moderate yields, whereby reagent 2a
exhibited a slightly better reactivity (entries 1–2). Based on our
relative to N-Me derivatives (8b
minimal impact on the yield of the corresponding products
8f ). KSAs derived from γ-lactam with a variety of α-
substituents such as benzyl (4a), phenyl (4e), methoxyethyl
4h and trimethysilyl 4j featured excellent reactivity
delivering the corresponding products in high yields.
Functional α-substituents such as allyl 4i and 3-TMS-
–d). The ring size of KSAs had
(
–g
experience with the activation of reagents
1 and 2a, we next
tested various Lewis acids such as triflimides16 and metal
complexes as catalysts (entries 3–7, 10–12). Among them,
trimethylsilyl triflimide displayed excellent catalytic properties,
leading to the desired product in 96% 19F NMR yield (entry 6).
Notably, 1 mol % of Mn and Fe catalysts with salen-type
ligands also efficiently catalyzed the reaction (entries 12–13).
Surprisingly, however, catalyst loadings higher than 1 mol %
significantly lowered product yields (entries 8–9).
(
)
( )
(
)
propargyl (4k) are fully compatible with this method as well.
Notably, KSA 4l derived from substituted 3,4-dihydroquinolin-
2-one was successfully trifluromethylated forming product 8l
in 87% isolated yield. The latter substructure is present in
many nitrogen heterocyclic compounds with
activity as plant disease control agents.17
a potential
Having found an effective catalyst system for the
trifluoromethylation of KSAs, we next examined the reaction
scope with various substituted KSAs, which were prepared by
lithiation of the corresponding lactams followed by trapping
with TMSCl. It is important to highlight that their synthesis was
straightforward, as the isolated crude compounds were pure
by elemental analysis and were directly used in the next
Having demonstrated that both reaction steps, silylation of
lactams and their subsequent trifluoromethylation, give
excellent yields, we further optimised the synthetic
applicability of this method and devised a one-pot, two-step
protocol for the direct α-trifluoromethylation of lactams
(Scheme 2). Thus, the chosen KSA is first formed in situ,
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 4
View Article Online
DOI: 10.1039/C6CC00700G
Journal Name
COMMUNICATION
Rf
I
O
solid state compound 9ak displays value of bond lengths and
angles in the expected ranges.
O
OTMS
Bn
Me
Me
2b-k
N
N
Rf
TMSNTf2 (1 mol %)
Bn
CH2Cl2, -78 °C to rt, 19 h
4a
9ab-ak
O
O
F
O
Me
Me
F
Me
F
F
F
F
N
N
N
O
O
S
F
F
F
Bn
Bn
F
F
F
Bn
F
OMe
Br
9ab, 91%
9ac, 88%
9ad, 81%
O
O
Me
Me
F
F
F
O
O
N
N
O
O
Me
F
F
N
O
F
F
Bn
F
F
Bn
O
O
F
Bn
F
OEt
OMe
9ae, 88%
9af, 77%
9ag, 91%
Figure 1 ORTEP view of the X-ray structure of compound 9ak. Hydrogen atoms
are omitted for clarity and thermal ellipsoids are drawn at the 50% probability
level. Only one of the two independent molecules in the asymmetric unit is
shown. Selected bond lengths [Å] and bond angles [°]: C16-C19 1.523(5), C16-
C21 1.553(5), C16-C17 1.545(5), C16-C15 1.548(5), F8-C20 1.326(5), F6-C19
1.369(4); C19-C16-C21 110.8(3), C19-C16-C17 112.2(3), C19-C16-C15 108.4(3),
C17-C16-C21 113.6(3). CCDC 1442867.
O
O
Me
F
O
F
Me
Me
F
F
F
F
N
N
X
O
O
N
N
N
CF3
F
Bn
F
F
Bn
Bn
F
Me
9ai
, 79% (X = O)
9aj, 76% (X = S)
9ak
, 95%
9ah, 82%
Reaction conditions: 4a (0.78 mmol, 0.78 M in DCM), 2b–k (0.6 mmol), TMSNTf2
(1 mol %), –78 °C to rt, 19 h.
Scheme 3 α-Perfluoroalkylation of KSA 4a
.
α-Fluoroalkylated lactams are expected to be valuable
followed by the addition of reagent and catalyst to affect the
targeted α-trifluoromethylation. This simple and
intermediates in the synthesis of
a wide range of
organofluorine compounds. To illustrate the practical
applicability of our methods, we designed a one-pot, multi-
step procedure towards the synthesis of fluorinated
pyrrolidine derivatives, compounds of potential interest in the
life sciences.6 As shown in Scheme 4, lactam 3a was
successfully transformed to the corresponding 3-
perfluoroethyl-substituted pyrrolidine 10 in overall 71%
straightforward procedure is applicable to various α-
substituted lactams as shown in Scheme 2, affording the
desired products with high overall efficiency. Interestingly, in
the case of α-propargyl substituted NMP (3k) silylation of the
terminal alkyne takes place in addition to α-
trifluorormethylation.
Recently, our group developed a series of new hypervalent
iodine(III)-Rf reagents based on the 1,3-dihydro-3,3-dimethyl-
1,2-benziodoxole scaffold, able to transfer a functionalised
tetrafluoroethyl unit.18 These reagents demonstrated very
similar reactivity in a number of transformations compared to
isolated yield via
a straightforward three-step protocol
including in situ silylation, α-fluoroalkylation and reduction
steps.
Me
O
F
1. LDA, THF, TMSCl, -78 °C tort, 6 h
2. , TMSNTf2 (1 mol %), -78°C to rt, 19 h
F
Me
N
2k
N
CF3
their established CF3 analogues
tetrafluoroethylated compounds. We therefore examined the
applicability of previously developed (2b 2f 2h) and newly
synthesised (2e 2g 2i ) fluoroalkyl hypervalent iodine(III)-Rf
1
and 2a providing access to
Bn 3. BH3-SMe2, 70 °C, 4 h
Bn
3a
10, 71%
–
d,
,
Scheme 4 Synthesis of (perfluoroethyl)pyrrolidine 10 via one-pot, multi-step
transformation of lactam 3a
.
,
,
–k
reagents in the α-perfluoroalkylation of lactams. KSA 4a was
chosen as a model substrate for these transformations, and
the results are summarized in Scheme 3. We were thus
pleased to find that all tested reagents displayed excellent
levels of reactivity towards KSA 4a giving the corresponding α-
fluoroalkylated products in moderate to high yields. The
obtained products contain tetrafluoroethyl moieties bearing S-
At the present stage we assume that the
perfluoroalkylation step proceeds via a similar mechanistic
scenario as we suggested in our recent work on the α-
trifluoromethylation of ketene silyl acetals derived from esters
and lactones.15 In the case of these Lewis acid-catalyzed
processes, TMSNTf2 activates the reagent to form a cationic
(iodonium) species, which should be able to engage a first
substrate molecule in a SET process, thus leading to the
formation of CF3 radicals.19 If this indeed happens, CF3 radicals
are then rapidly trapped by a second substrate molecule
Ar (9ab), O-Ar (9ac–af), CH2-Ar (9ag), and N-heterocyclic (9ah)
substituents and can be used for further functionalizations.
Products 9ai and 9aj are particularly interesting due to the
presence of a fluorescent moiety based on coumarin, which
can serve for the labelling of biological targets.
subsequently taking part in a second SET with reagent
2 pre-
Finally, crystalline α-perfluoroethyl lactam 9ak was
obtained in high (95%) yield from reagent 2k and was
characterised by X-ray analysis (Figure 1). X-Ray crystal
structures of acyclic and cyclic all-carbon-substituted α-
perfluoroethyl carbonyl compounds have not been reported
previously, as confirmed by a CCDC database search. In the
activated by the catalyst. The thereby formed
silyloxycarbenium intermediate generates the desired product
–
in the presence of the triflimide anion (NTf2 ) via desilylation
and concomitant regeneration of the catalyst. Additionally,
one should also take into account the silylating properties of
electron-rich lactam-derived KSAs, and hence their ability to
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 4
View Article Online
DOI: 10.1039/C6CC00700G
COMMUNICATION
Journal Name
Mihara, M. Hatazawa, D. Yamazaki, H. Kishikawa, K. Domon,
H. Watanabe, N. Sasaki, T. Murata, K. Araki, E. Shimojo, T.
Ichihara, T. Ishikawa, K. Shibuya, U. Goergens, P. Bruechner,
R. Fischer, J.-R. Jansen, T. Kapferer, S. Maechling, M. Maue
and A. Voerste, WO Pat., 2012035011 (A1), 2012.
(a) K. Mikami, Y. Tomita, Y. Ichikawa, K. Amikura and Y. Itoh,
Org. Lett., 2006, 8, 4671; (b) Y. Itoh and K. Mikami,
Tetrahedron, 2006, 62, 7199; (c) Y. Itoh and K. Mikami, J.
Fluorine Chem., 2006, 127, 539; (d) Y. Itoh and K. Mikami,
Org. Lett., 2005, 7, 649; (e) Y. Itoh and K. Mikami, Org. Lett.,
transfer the silyl group to reagent 2. The latter assumption can
explain the background reaction in the non-catalyzed process.
In conclusion, we have developed a method allowing facile
α-fluoroalkylation of lactam-derived KSAs by hypervalent
iodine reagents, which proceeds with high efficiency in the
presence of 1 mol % of TMSNTf2 as the catalyst or with
moderate performance under catalyst-free reaction
conditions. Moreover, we have devised a one-pot protocol
that allows the installation of the trifluoromethyl group
directly onto a variety of lactams, requiring no isolation or
purification steps of the intermediates. Given the simplicity,
efficiency and the broad scope of this protocol, we envisage
that it will be extensively used by synthetic chemists working
in the fields of medicinal chemistry, agrochemistry and
material sciences.
7
2005, , 4883; (f) J.-A. Ma and D. Cahard, Chem. Rev., 2004,
7
104, 6119; (g) K. Miura, Y. Takeyama, K. Oshima and K.
Utimoto, Bull. Chem. Soc. Jpn., 1991, 64, 1542; (h) K. Miura,
M. Taniguchi, K. Nozaki, K. Oshima and K. Utimoto,
Tetrahedron Lett., 1990, 31, 6391.
8
9
(a) P. V. Pham, D. A. Nagib and D. W. C. MacMillan, Angew.
Chem., Int. Ed., 2011, 50, 6119; (b) D. A. Nagib, M. E. Scott
and D. W. C. MacMillan, J. Am. Chem. Soc., 2009, 131, 10875.
(a) L. Li, Q.-Y. Chen and Y. Guo, J. Org. Chem., 2014, 79, 5145.
(b) K. Sato, A. Tarui, M. Omote and A. Ando, Synthesis, 2010,
11, 1865; (c) K. Sato, T. Yuki, R. Yamaguchi, T. Hamano, A.
Tarui, M. Omote, I. Kumadaki and A. Ando, J. Org. Chem.,
2009, 74, 3815; (d) K. Sato, M. Higashinagata, T. Yuki, A.
Tarui, M. Omote, I. Kumadaki and A. Ando, J. Fluorine Chem.,
2008, 129, 51.
This work was supported by ETH Zürich. D.K. thanks the
Swiss National Science Foundation (SNSF) for a fellowship. We
thank Dr. V. Matoušek (CF Plus Chemicals, Brno, Czech
Republic) for preliminary experiments and advice, P. Hájek
(group of Dr. P. Beier, IOCB AS CR Prague, Czech Republic) for
experimental contributions, and L. Sigrist for X-ray analysis.
10 For recent reviews, see: (a) N. Früh, J. Charpentier and A.
Togni, Top. Curr. Chem., 2015, DOI: 10.1007/128_2015_658;
(b) J. Charpentier, N. Früh and A. Togni, Chem. Rev., 2015,
115, 650; (c) V. Bizet, T. Besset, J.-A. Ma and D. Cahard, Curr.
Top. Med. Chem., 2014, 14, 901; (d) C. Zhang, ARKIVOC,
2014, 453; (e) S. Barata-Vallejo, B. Lantaño and A. Postigo,
Chem. Eur. J., 2014, 20, 16806; (f) T. Liang, C. N. Neumann
and T. Ritter, Angew. Chem., Int. Ed., 2013, 52, 8214; (g) N.
Shibata, A. Matsnev and D. Cahard, Beilstein J. Org. Chem.,
Notes and references
1
(a) M. Cametti, B. Crousse, P. Metrangolo, R. Milani and G.
Resnati, Chem. Soc. Rev., 2012, 41, 32; (b) Y. Li, Acc. Chem.
Res., 2012, 45, 723; (c) S. Schlögl, R. Kramer, D. Lenko, H.
Schroettner, R. Schaller, A. Holzner and W. Kern, Eur. Polym.
J., 2011, 47, 2321; (d) R. Berger, G. Resnati, P. Metrangolo, E.
Weber and J. Hulliger, Chem. Soc. Rev., 2011, 40, 3496; (e) D.
O’Hagan, J. Fluorine Chem., 2010, 131, 1071; (f) M. G. Dhara
and S. Banerjee, Prog. Polym. Sci., 2010, 35, 1022; (g) F.
Babudri, G. M. Farinola, F. Naso and R. Ragni, Chem.
Commun., 2007, 1003; (h) P. Kirsch and A. Hahn, Eur. K. Org.
Chem., 2005, 3100.
2010, 6, 65; (h) J.-A. Ma and D. Cahard, J. Fluorine Chem.,
2007, 128, 975.
11 (a) V. Matoušek, E. Pietrasiak, R. Schwenk and A. Togni, J.
Org. Chem., 2013, 78, 6763; (b) P. Eisenberger, I. Kieltsch, R.
Koller, K. Stanek and A. Togni, Org. Synth. 2011, 88, 168; (c)
P. Eisenberger, S. Gischig and A. Togni, Chem. - Eur. J., 2006,
12, 2579.
12 (a) R. Koller, PhD thesis, No. 19219 ETH Zurich, 2010; (b) I.
Kieltsch, P. Eisenberger, K. Stanek and A. Togni, Chimia,
2008, 62, 260; (c) I. Kieltsch, PhD thesis, No. 17990 ETH
Zurich, 2008; (d) I. Kieltsch, P. Eisenberger and A. Togni,
Angew. Chem., Int. Ed., 2007, 46, 754.
2
(a) J. Wang, M. V. A. Soloshonok and H. Liu, Chem. Rev.,
2014, 114, 2432; (b) S. Purser, P. R. Moore, S. Swallow and V.
Gouverneur, Chem. Soc. Rev., 2008, 37, 320; (c) W. K.
Hagmann, J. Med. Chem., 2008, 51, 4359; (d) D. O’Hagan,
Chem. Soc. Rev., 2008, 37, 308; (e) K. Müller, C. Faeh and F.
Diederich, Science, 2007, 317, 1881; (f) C. Isanbor and D.
O’Hagan, J. Fluorine Chem., 2006, 127, 303.
13 P. Eisenberger, PhD thesis, No. 17371 ETH Zurich, 2007.
14 N. Früh and A. Togni, Angew. Chem., Int. Ed., 2014, 53
,
3
4
5
(a) G. Theodoridis, Adv. Fluorine Chem., 2006,
Jeschke, ChemBioChem, 2004, , 570; (c) P. Maienfisch and
R. G. Hall, Chimia, 2004, 58 93; (d) T. Hiyama,
Organofluorine Compounds: Chemistry and Applications,
Springer, Berlin, 2000, 183.
(a) C. Zhang, D.-M. Zhuang, J. Li, S.-Y. Chen, X.-L. Du, J.-Y.
Wang, J.-Y. Li, B. Jiang and J.-H. Yao, Org. Biomol. Chem.,
2013, 11, 5621; (b) H. Hoeffkes and D. Fuhr, DE Pat.,
102006038325 (A1), 2007; (c) P.-H. Liang, L.-W. Hsin and C.-
Y. Cheng, Bioorg. Med. Chem. 2002, 3267.
T. D. Aicher, R. C. Anderson, J. Gao, S. S. Shetty, G. M.
Coppola, J. L. Stanton, D. C. Knorr, D. M. Sperbeck, L. J.
Brand, C. C. Vinluan, E. L. Kaplan, C. J. Dragland, H. C.
Tomaselli, A. Islam, R. J. Lozito, X. Liu, W. M. Maniara, W. S.
Fillers, D. DelGrande, R. E. Walter and W. R. Mann, J. Med.
Chem., 2000, 43, 236.
2, 121; (b) P.
10813.
15 D. Katayev, V. Matoušek, R. Koller and A. Togni, Org. Lett.,
2015, 17, 5898.
16 For recent review on usage of metal triflimides in catalysis,
see: S. Antoniotti, V. Dalla and E. Duñach, Angew. Chem., Int.
Ed., 2010, 49, 7860.
17 U. Ichiro, Y. Chinami and N. Satoshi, JP Pat., 2011148714 (A),
2011.
18 V. Matoušek, J. Václavík, P. Hájek, J. Charpentier, Z. E. Blastik,
E. Pietrasiak, A. Budinská, P. Beier and A. Togni, Chem Eur. J.,
2016, 22, 417.
19 (a) O. Sala, N. Santschi, S. Jungen, H. P. Lüthi, M. Lannuzzi, N.
Hauser and A. Togni, Chem. - Eur. J., 2016, 22, 390; (b) O.
Sala, H. P. Lüthi, A. Togni, M. Lannuzzi and J. Hutter, J.
Comput. Chem., 2015, 36, 785; (c) H. Pinto de Magalhães, H.
P. Lüthi and A. Togni, J. Org. Chem., 2014, 79, 8374.
5
,
6
For selected patents on bioactive β-fluoroalkylated
alkylamine derivatives, see: (a) U. Goergens, J. Mihara, T.
Murata, D. Yamazaki, Y. Yoneta, K. Araki, N. Sasaki, K.
Domon, M. Hatazawa, E. Shimojo, T. Ichihara, A. Teruyuki, M.
Ataka and K. Shibuya, US Pat., 20150073139 (A1), 2015; (b) J.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins