Copper-Catalyzed Trifluoromethylation of Aliphatic N-Arylhydrazones: A Concise Synthetic Entry to 2-Trifluoromethylindoles from Simple Aldehydes

Article abstract of DOI:10.1002/adsc.201500237

The copper-catalyzed C(sp²)-H trifluoromethylation of N,N-disubstituted hydrazones using the Togni reagent is demonstrated to proceed efficiently for aliphatic aldehyde-derived substrates. The success of the reactions relied on the choice of the N,N-diphenylamino group as the terminal hydrazone amino group where N,N-dialkylamino groups were preferred for (hetero)aromatic aldehyde-derived substrates. In addition, the trifluoromethylated N-arylhydrazones are shown to be ideal substrates for Fischer indole synthesis allowing a straightforward, three-step access to 2-trifluoromethylindole derivatives from simple aldehydes.

Full text of DOI:10.1002/adsc.201500237

UPDATES
DOI: 10.1002/adsc.201500237
Copper-Catalyzed Trifluoromethylation of Aliphatic
N-Arylhydrazones: A Concise Synthetic Entry to
2-Trifluoromethylindoles from Simple Aldehydes
Alexis Prieto,a MØlissa Landart,a Olivier Baudoin,a Nuno Monteiro,a,*
and Didier Bouyssia,*
a
UniversitØ Claude Bernard Lyon 1, CNRS UMR 5246. Institut de Chimie et Biochimie MolØculaires et
SupramolØculaires, CPE Lyon, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France
E-mail: nuno.monteiro@univ-lyon1.fr or didier.bouyssi@univ-lyon1.fr
Received: March 9, 2015; Revised: June 15, 2015; Published online: September 11, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500237.
2
À
Abstract: The copper-catalyzed C(sp ) H trifluoro-
methylation of N,N-disubstituted hydrazones using
the Togni reagent is demonstrated to proceed effi-
ciently for aliphatic aldehyde-derived substrates.
The success of the reactions relied on the choice of
the N,N-diphenylamino group as the terminal hy-
drazone amino group where N,N-dialkylamino
groups were preferred for (hetero)aromatic alde-
hyde-derived substrates. In addition, the trifluoro-
methylated N-arylhydrazones are shown to be ideal
substrates for Fischer indole synthesis allowing
a straightforward, three-step access to 2-trifluoro-
methylindole derivatives from simple aldehydes.
leading edge of many new developments in the phar-
maceutical and agrochemical industries.[4] In this con-
text, there is an increasing need for synthetically
useful CF3-containing building blocks that would be
easily accessible from simple starting materials.
Owing to the wide synthetic versatility of hydrazones,
the development of a general method for the direct
C(sp ) H trifluoromethylation of these compounds
would significantly expand their application scope to
include access to valuable organofluorine molecules.
Although trifluoromethylhydrazones can be obtained
from the corresponding trifluoromethyl ketones
(TFMKs), this approach often suffers from difficulties
associated with the preparation of these precursors on
account of their peculiar properties.[6] We recently de-
veloped a very mild procedure for the trifluoromethy-
lation of aldehyde N,N-dialkylhydrazones using the
Togni hypervalent iodine reagent (1)[7] under copper
chloride catalysis.[8] However, a significant drawback
of the method lay in the low efficiencies obtained so
2
[5]
À
Keywords: fluorine; homogeneous catalysis; hydra-
zones; hypervalent compounds
Hydrazones constitute an important class of com- far for aliphatic aldehyde hydrazones (2), the sub-
pounds known to exhibit a wide range of interesting strate scope being primarily limited to (hetero)aro-
biological activities including antitumor, antibiotic, matic derivatives (Scheme 1).[8a] Access to trifluoro-
anti-inflammatory, antimalarial and anti-HIV proper- methylated aliphatic aldehyde hydrazones (3) would
ties.[1] They are useful molecules for drug design, no- greatly improve the synthetic utility of the methodol-
tably as promising hydrolytically-labile tethers for ogy. For instance, these compounds are particularly
drug release.[2] Among other interesting features, they attractive owing to their inherent capability to tauto-
are readily available intermediates in synthetic organ-
ic chemistry, involved in a plethora of applications,
mainly as carbonyl surrogates, but also as precursors
of nitrogen-containing compounds, which include sub-
stituted hydrazines, primary amines, and nitrogen het-
erocycles.[3]
In recent years, CF3-containing compounds have
been receiving increased attention, notably because of
their important applications as biologically active
agents and new materials. They are currently at the Scheme 1. Trifluoromethylation of N,N-dialkylhydrazones.
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Alexis Prieto et al.
merize to the ene-hydrazine form making them po-
Next, the substrate scope for aldehyde N,N-diphe-
tential precursors of a variety of valuable fluorinated nylhydrazones was explored. The results collected in
heterocyclic compounds[9] through diverse cyclization Table 2 demonstrate the generality of the reaction.
processes that include, but are not limited to, the Linear and branched-chain primary aliphatic alde-
Fischer indole-type heteroannulations.[10,11]
hyde derivatives were first investigated. Essentially all
We report herein the successful extension of the substrates furnished the corresponding trifluorome-
substrate scope of our hydrazone trifluoromethylation thylated products (3e–3o) in moderate to excellent
process to include aliphatic derivatives, thereby dem- yields and demonstrated an excellent degree of func-
onstrating the general utility of the method. Interest- tional group tolerance. Various substituents and func-
ingly, the choice of N,N-diphenylamino as the termi- tional groups were tolerated, including thiomethyl
nal hydrazone amino group appeared to be the key to (3h), benzyloxy (3i), halide (3g), and free hydroxy
efficient promotion of these reactions, and their syn- (3l). Moreover, bis-trifluoromethylation occurred in
thetic utility was then illustrated as a means of access- acceptable yield (3j) from a substrate containing two
ing 2-trifluoromethylindole derivatives from simple hydrazone moieties. Notably, no desired product (3k)
aliphatic aldehydes.
could be isolated from the complex reaction mixture
Initial attempts at trifluoromethylating N,N-dialkyl obtained for the citronellal-derived hydrazone, which
hydrazones using hydrocinnamaldehyde-derived pre- probably reflects competition between two reactive
cursors under our previously established reaction con- functional groups (hydrazone and alkene[13]) during
ditions (10 mol% CuCl, CHCl3, room temperature) the trifluoromethylation process. This assertion is sup-
led to reaction mixtures containing the expected ported by the reaction of the saturated 7-hydroxyci-
product (3a, 3b) in only low amounts (Table 1, en- tronellal derivative that delivered the desired com-
tries 1 and 2) among other undesired products. Pleas- pound (3l) in good yield.
ingly, we found that replacement of the N,N-dialkyl-
In addition, (hetero)aromatic derivatives of acetal-
amino with an N,N-diphenylamino group could sup- dehyde hydrazones 3n and 3o attested to the compati-
press formation of side products and dramatically im- bility of highly enolizable hydrazones, albeit lower
prove the yield of the desired reaction.[12] Thus, hy- yields were obtained in these cases. Moreover, it is of
drocinnamaldehyde
N,N-diphenylhydrazone note that the heterocyclic ring in 3o remained un-
underwent complete and clean conversion to the cor- touched. The reaction also tolerated secondary alde-
responding trifluoromethylated product 3c (65% hyde hydrazones (3p and 3q), whereas the sterically
yield) (Table 1, entry 3). Furthermore, increasing the hindered pivaldehyde derivative displayed poor reac-
amount of catalyst had also a significant effect on the tivity at the azomethine centre, giving rise to an in-
yield and rate of the reaction, furnishing 81% of 3c tractable mixture of trifluoromethylated products
(65% isolated yield) in less than two hours (Table 1, upon increasing the reaction temperature to 508C.
entry 4). Interestingly, reaction of the N-methyl-N- The mixture contained only small amounts of the de-
phenylhydrazone also proceeded in relatively good sired product (3r) among several side products pre-
yield (Table 1, entry 5).
sumably arising from further, undesired trifluorome-
thylation at the electron-rich aminophenyl rings.
Some non-aliphatic trifluoromethylated compounds
3s, 3t, and 3u, derived from formaldehyde, glyoxal,
and ethyl glyoxylate, respectively, were also synthe-
sized to further demonstrate the broad applicability
of the method. It is worthy of note that bis-trifluoro-
methylation was not observed in the case of glyoxal
bis-hydrazone despite the use of a two-fold excess of
the Togni reagent. An X-ray structure was obtained
for 3e establishing the geometry of the hydrazone C=
N bond as E (Figure 1).[14] Finally, the robustness of
this transformation was further demonstrated by per-
forming the synthesis of 3m on a semi-preparative
7.5 mmol scale (52% isolated yield).
Possible applications of the trifluoromethylated
N,N-diphenylhydrazones were next investigated. Ap-
plications of great interest would include access to tri-
fluoromethyl ketones as well as indole derivatives.
Trifluoromethyl ketones are important building
blocks for the synthesis of trifluoromethylated com-
pounds[6] but have also shown interesting biological
Table 1. Screening of hydrocinnamaldehyde hydrazones.
Entry NR2 =
Cat.
Time
[h]
Product; Yield
[%][a]
[mol%]
1
2
3
4
5
NMe2
NBn2
NPh2
NPh2
10
10
10
20
15
15
15
2
3a; 27
3b; 30
3c; 65
3c; 81 (65)
3d; 60 (53)
N(Me)Ph 20
2
[a]
Yields were determined by 19F NMR spectroscopy of the
crude reaction mixture using a,a,a-trifluorotoluene as an
internal standard. Yields in parentheses refer to pure iso-
lated products.
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Copper-Catalyzed Trifluoromethylation of Aliphatic N-Arylhydrazones
Table 2. Substrate scope for aldehyde N,N-diphenylhydra-
zones.[a]
Figure 1. X-Ray representation of 3e (ellipsoids 50% proba-
bility).
properties, notably as reversible competitive inhibi-
tors of several classes of enzymes.[15] In this context,
the development of new methods to access these val-
uable compounds remains an area of current interest.
Although hydrolysis of arylhydrazones has, to the
best of our knowledge, not been reported in the liter-
ature, the carbonyl group was expected to be restored
under acidic conditions. As for 2-trifluoromethylin-
doles, they are core structures of pharmaceutically im-
portant molecules,[16,17] and were also expected to be
accessible upon Brønsted acid treatment through
Fischer-type cyclization.[18]
Our preliminary studies focused on the behaviour
of phenylacetaldehyde N,N-diphenylhydrazone 3n as
a model substrate in hydrochloric acid medium
(Table 3). Although no reaction was observed in a 1:1
mixture of 1N HCl/THF at room temperature, the
use of a higher concentration of hydrochloric acid al-
lowed cleavage of the diphenylhydrazone protective
group to yield a 1:2.5 mixture of the corresponding
trifluoromethyl ketone (4) and its hydrate derivative
5 in a nearly quantitative combined yield (Table 3, en-
tries 1 and 2). Ketone 4 could then be obtained in
67% isolated yield following dehydration of 5 from
the mixture (MgSO4, refluxing CHCl3, 1 h). Diminish-
ing the amount of water favoured formation of
ketone 4 over its hydrate 5 (Table 3, entry 3) but far
more interesting was the formation of 2-trifluorome-
thylindole 6a (40% yield) under these relatively mild
conditions. Pleasingly, repeating the reaction in the
absence of moisture by using dry HCl gas led to rapid
(less than 5 min), complete conversion of the hydra-
zone to the indole derivative, which was then isolated
in a very good 79% yield. The scope of the reaction
[a]
Reaction conditions: 2 (0.5 mmol), 1 (0.6 mmol), and
CuCl (0.1 mmol) in 3 mL CHCl3 at 258C for 2 h. Yields
were determined by 19F NMR of the crude mixtures
using a,a,a-trifluorotoluene as an internal standard. Iso-
lated yields of pure compounds are given in parentheses.
Glutaraldehyde bis-hydrazone as starting material;
2.4 equiv. of the Togni reagent were used.
Product contaminated by trace amounts of unidentified
fluorinated side-products.
Reaction performed at 508C.
The gem-bis-trifluoromethylated product was also ob-
[b]
[c]
[d]
[e]
tained in 18% isolated yield.
2 equiv. of the Togni reagent were used.
[f]
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Alexis Prieto et al.
Table 3. Ketone deprotection versus Fischer indole cycliza-
was then briefly evaluated giving rise to an array of
substituted N-aryl- (6a–d), but also N-alkylindoles
(6e) in good to excellent yields (Table 4).
tion under acidic conditions.[a]
In summary, we have shown that our copper-cata-
lyzed hydrazone trifluoromethylation process can also
include aliphatic aldehyde derivatives as important
substrates, thereby demonstrating the wide applicabil-
ity of the method. Trifluoromethylated N-arylhydra-
zones have been shown to be suitable starting prod-
ucts in the synthesis of trifluoromethyl ketones as
Entry Reaction
conditions
Yield [%] Yield [%] well as 2-trifluoromethylindole derivatives, the later
of 4+5
of 6a
becoming accessible in three steps from simple alde-
hydes.
1
2
3
4
HCl 1N/THF (1:1), 24 h
HCl 6N/THF (1:1), 24 h
–
–
95 (67[b])
trace
40
HCl 12N/THF (1:9), 24 h 60[c]
Experimental Section
HCl (g), THF, 5 min
<5
91 (79)
[a]
Yields and ratios were determined by 19F NMR spectros-
copy of the crude reaction mixture using a,a,a-trifluoro-
toluene as an internal standard. Isolated yields of pure
compounds are given in parentheses.
Yield of 4 after dehydration of 5 upon heating the mix-
ture (ratio 4:5 was 1:2.5) over MgSO4 in refluxing CHCl3.
Ratio 4:5 was 4.5:1.
General Procedure 1
Preparation of trifluoromethylated hydrazones (3): In
a glass tube, the Togni reagent 1 (184.6 mg, 0.6 mmol) and
copper chloride (10 mg, 0.1 mmol) were successively added
to a solution of the selected hydrazone (0.5 mmol) in CHCl3
(3 mL). The reactor was flushed with argon and sealed. The
reaction mixture was stirred at room temperature for the ap-
propriate time and then washed with saturated sodium bi-
carbonate solution (3”10 mL). The organic layer was dried
over MgSO4 and concentrated under vacuum. The residue
was purified by flash chromatography (silica gel, appropriate
mixture of pentane/dichloromethane) to afford the corre-
sponding trifluoromethylated hydrazone.
[b]
[c]
Table 4. Substrate scope for 2-trifluoromethylindoles.[a]
General Procedure 2
Preparation of 2-CF3-indoles (6) from trifluoromethylhy-
drazones: In a glass tube, the selected hydrazone (0.3 mmol)
was dissolved in THF (1 mL), then HCl gas (generated
through dropwise addition of concentrated H2SO4 to NaCl)
was bubbled through the solution via a cannula at room
temperature until a cloudy yellow solution was obtained
(approximately 5 min). The reaction mixture was then
washed with saturated sodium bicarbonate solution (3”
5 mL). The organic layer was dried over MgSO4 and concen-
trated under vacuum. The residue was purified by flash
chromatography (silica gel, appropriate mixture of pentane/
dichloromethane) to afford the corresponding trifluorome-
thylindole.
Acknowledgements
This research was assisted financially by a grant to A. P.
from the French Ministry of Higher Education and Research
(MESR). We thank G. Pilet (Laboratoire des multimatØriaux
et interfaces, UniversitØ Lyon 1) for the X-ray crystallograph-
ic analysis. Emeric Jeamet (UniversitØ Lyon 1) is acknowl-
edged for preliminary experiments.
[a]
Reactions performed on a 0.3 mmol scale. Yields were
determined by 19F NMR of the crude mixtures using
a,a,a-trifluorotoluene as an internal standard. Isolated
yields of pure compounds are given in parentheses.
[b]
13% of the corresponding trifluoromethyl ketone were
also formed.
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Copper-Catalyzed Trifluoromethylation of Aliphatic N-Arylhydrazones
References
zoles: a) G. Zhang, Y. Zhao, H. Ge, Angew. Chem.
2013, 125, 2619; Angew. Chem. Int. Ed. 2013, 52, 2559;
b) R. Vanjari, T. Guntreddi, S. Kumar, K. N. Singh,
Chem. Commun. 2015, 51, 366; cinnolines: c) G.
Zhang, Y. Zhao, H. Ge, Angew. Chem. 2012, 124, 8443;
Angew. Chem. Int. Ed. 2012, 51, 8318.
[1] For recent reviews, see: a) G. Verma, A. Marella, M.
Shaquiquzzaman, M. Akhtar, M. R. Ali, M. M. Alam,
J. Pharm. Bioallied Sci. 2014, 6, 69; b) V. J. Negi, A. K.
Sharma, J. S. Negi, V. Ram, Int. J. Pharm. Chem. 2012,
4, 100.
[2] a) K. R. West, S. Otto, Curr. Drug Discov. Technol.
2005, 2, 123; b) J. B. Matson, S. I. Stupp, Chem.
Commun. 2011, 47, 7962; c) V. Rao N, S. R. Mane, A.
Kishore, J. D. Sarma, R. Shunmugam, Biomacromole-
cules, 2012, 13, 221.
[12] By-products supposedly originate from competitive N-
dealkylation pathways that are not yet fully under-
stood. Further mechanistic studies are currently under-
way to better understand the observed behaviour of ali-
phatic aldehyde N,N-dialkylhydrazones; see the Sup-
porting Information.
[3] For reviews of the rich chemistry of hydrazones, see:
a) R. Lazny, A. Nodzewska, Chem. Rev. 2010, 110,
1386; b) R. Brehme, D. Enders, R. Fernandez, J. M.
Lassaletta, Eur. J. Org. Chem. 2007, 5629.
[4] a) Fluorine in Medicinal Chemistry and Chemical Biol-
ogy, (Ed.: I. Ojima), 2009, Wiley, Chichester; b) S.
Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem.
Soc. Rev. 2008, 37, 320; c) W. K. Hagmann, J. Med.
Chem. 2008, 51, 4359; d) K. Müller, C. Faeh, F. Dieder-
ich, Science 2007, 317, 1881.
[13] For reviews on the trifluoromethylation of alkenes, see:
a) M. Sodeoka, H. Egami, Angew. Chem. 2014, 126,
8434–8449; Angew. Chem. Int. Ed. 2014, 53, 8294; b) E.
Merino, C. Nevado, Chem. Soc. Rev. 2014, 43, 6598.
[14] CCDC 1052522 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif,
see also the Supporting Information.
[15] a) C. A. Veale, J. R. Damewood Jr, G. B. Steelman, C.
Bryant, B. Gomes, J. Williams, J. Med. Chem. 1996, 39,
86; b) G. S. Garrett, S. J. McPhail, K. Tornheim, P. E.
Correa, J. M. McIver, Bioorg. Med. Chem. Lett. 1999, 9,
301; c) R. R. Frey, C. K. Wada, R. B. Garland, M. L.
Curtin, M. R. Michaelides, J. Li, L. J. Pease, K. B.
Glaser, P. A. Marcotte, J. J. Bouska, S. S. Murphy, S. K.
Davidsen, Bioorg. Med. Chem. Lett. 2002, 12, 3443;
d) R. M. Wadkins, J. L. Hyatt, C. C. Edwards, L. Tsur-
kan, M. R. Redinbo, C. E. Wheelock, P. D. Jones, B. D.
Hammock, P. M. Potter, Mol. Pharmacol. 2007, 71, 713;
e) Y.-M. Shao, W.-B. Yang, T.-H. Kuo, K.-C. Tsai, C.-H.
Lin, A.-S. Yang, P. -H. Liang, C.-H. Wong, Bioorg. Med.
Chem. 2008, 16, 4652.
[16] a) Y. Fukuda, H. Furuta, F. Shiga, Y. Oomori, Y.
Kusama, H. Ebisu, S. Terashima, Bioorg. Med. Chem.
Lett. 1997, 7, 1683; b) Y. Fukuda, H. Furuta, Y.
Kusama, H. Ebisu, Y. Oomori, S. Terashima, J. Med.
Chem. 1999, 42, 1448; c) M. A. Akanmu, C. Songkram,
H. Kagechika, K. Honda, Neurosci. Lett. 2004, 364,
199.
[17] For recent, leading references on 2-trifluoromethyl
indole synthesis, see: a) B. Zhang, A. Studer, Org. Lett.
2014, 16, 1216; b) T. Iqbal, S. Choi, E. Ko, E. J. Cho,
Tetrahedron Lett. 2012, 53, 2005; c) D. A. Nagib,
D. W. C. MacMillan, Nature 2011, 480, 224; d) Z. Chen,
J. Zhu, H. Xie, S. Li, Y. Wu, Y. Gong, Adv. Synth.
Catal. 2011, 353, 325; e) X. Mu, S. Chen, X. Zhen, G.
Liu, Chem. Eur. J. 2011, 17, 6039; f) R. Shimizu, H.
Egami, T. Nagi, J. Chae, Y. Hamashima, M. Sodeoka,
Tetrahedron Lett. 2010, 51, 5947.
[18] Previous examples of Fischer (2-trifluoromethyl)indole
syntheses were limited to free (NH)-indole derivatives:
a) H. Jiang, Y. Wang, W. Wan, J. Hao, Tetrahedron
2010, 66, 2746; b) B. I. Usachev, D. L. Obydennov, V. Y.
Sosnovskikh, J. Fluorine Chem. 2012, 135, 278.
[5] For recent reviews of trifluoromethylation processes,
see: a) T. Furuya, A. S. Kamlet, T. Ritter, Nature 2011,
473, 470; b) O. A. Tomashenko, V. V. Grushin, Chem.
Rev. 2011, 111, 4475; c) Y. MacØ, E. Magnier, Eur. J.
Org. Chem. 2012, 2479; d) N. Shibata, A. Matsnev, D.
Cahard, Beilstein J. Org. Chem. 2010, 6, 65; e) A.
Studer, Angew. Chem. 2012, 124, 9082; Angew. Chem.
Int. Ed. 2012, 51, 8950; f) G. Landelle, A. Panossian, S.
Pazenok, J.-P. Vors, F. R. Leroux, Beilstein J. Org.
Chem. 2013, 9, 2476; g) T. Liang, C. N. Neumann, T.
Ritter, Angew. Chem. 2013, 125, 8372; Angew. Chem.
Int. Ed. 2013, 52, 8214; h) H. Liu, Z. Gu, X. Jiang, Adv.
Synth. Catal. 2013, 355, 617; see also refs.[7,13]
[6] For a review on the chemistry of trifluoromethyl ke-
tones, see: C. B. Kelly, M. A. Mercadante, N. E. Lead-
beater, Chem. Commun. 2013, 49, 11133.
[7] For an exhaustive review of trifluoromethylation reac-
tions involving the Togni reagents, see: J. Charpentier,
N. Früh, A. Togni, Chem. Rev. 2015, 115, 650.
[8] a) E. Pair, N. Monteiro, D. Bouyssi, O. Baudoin,
Angew. Chem. 2013, 125, 5454; Angew. Chem. Int. Ed.
2013, 52, 5346; for an extension of the methodology to
the b-trifluoromethylation of a,b-unsaturated hydra-
zones, see: b) A. Prieto, E. Jeamet, N. Monteiro, D.
Bouyssi, O. Baudoin, Org. Lett. 2014, 16, 4770.
[9] Fluorinated heterocyclic compounds: Synthesis, chemis-
try, and applications (Ed.: V. A.Petrov), 2009, Wiley,
Hoboken.
[10] a) B. Robinson, The Fischer Indole Synthesis, Wiley,
New York, 1982; b) D. L. Hughes, Org. Prep. Proced.
Int. 1993, 25, 607; c) G. R. Humphrey, J. T. Kuethe,
Chem. Rev. 2006, 106, 2875. For a general review of
indole syntheses, see d) D. F. Taber, P. K. Tirunahari,
Tetrahedron 2011, 67, 7195.
[11] For other recent examples of heterocycle synthesis
through cyclization of enolizable hydrazones, see: pyra-
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