Fluorinated β-nitro amines by a selective ZrCl4-catalyzed aza-Henry reaction of (E)-trifluoromethyl aldimines

Article abstract of DOI:10.1039/c2ob26397a

ZrCl₄ was found to be an ideal catalyst to promote aza-Henry reactions between trifluoromethyl aldimines and some nitro alkanes giving new fluorinated β-nitro amines. The reaction is strongly influenced by the CF₃ group, the yield by

Full text of DOI:10.1039/c2ob26397a

View Online / Journal Homepage
Dynamic Article Links
Organic &
Biomolecular
Chemistry
Cite this: DOI: 10.1039/c2ob26397a
www.rsc.org/obc
COMMUNICATION
Fluorinated β-nitro amines by a selective ZrCl4-catalyzed aza-Henry reaction
of (E)-trifluoromethyl aldimines†
Stefania Fioravanti,* Lucio Pellacani* and Maria Cecilia Vergari
Received 18th July 2012, Accepted 6th September 2012
DOI: 10.1039/c2ob26397a
interesting starting materials to synthesize differently substituted
trifluoromethyl amino compounds.13
ZrCl4 was found to be an ideal catalyst to promote aza-
Henry reactions between trifluoromethyl aldimines and some
nitro alkanes giving new fluorinated β-nitro amines. The
reaction is strongly influenced by the CF3 group, the yield by
the alkyl chain of the nitro compound, while the stereochemi-
cal outcome seems to be unaffected, the anti isomer being
always the major product.
The aza-Henry condensation was tested between (E)-N-(2,2,2-
trifluoroethylidene)cyclohexanamine (1a) and nitromethane by
using different reaction conditions, as reported in Table 1.
At first, the aza-Henry reaction was attempted without a
solvent and an added base, to test if the same imine could gener-
ate in situ the nitronate,14 but no reaction was observed and both
reagents were quantitatively recovered (entry 1). Then, different
inorganic or organic bases in polar protic15 (entries 2 and 3) or
aprotic solvents (entries 5 and 6) were added to the reaction
mixture to promote the formation of nucleophilic species, but
both aldimine 1a and nitromethane were quantitatively recovered
under all conditions. Therefore, the aza-Henry condensation was
tested under acid catalysis conditions with the aim of increasing
the electrophilicity of 1a. Oxalic acid was tested as an organic
protic catalyst (entry 8) but no reaction occurred and the
Fluorine-containing amino compounds are of particular interest
among the relevant fluorinated molecules.1 In fact, it has been
well demonstrated that a selective substitution of hydrogen by
fluorine induces deep modifications in chemical, physical, and
biological properties of organic compounds.2 These modifi-
cations are due to the fluorine atoms nature, which produces pro-
found stereo-electronic effects on the neighboring groups,
leading to special performances of these compounds in different
fields, from the organic, to the pharmaceutical ones.3 In particu-
lar, a trifluoromethyl group usually increases the lipophilicity4 of
a parent molecule and can often avoid undesired metabolic trans-
formations observed for analogous unfluorinated compounds.
Unfortunately, most of the approaches to synthesize CF3-con-
taining organic compounds5 suffer from serious drawbacks,
above all, the choice of the starting materials. Thus, the most
common methods involve the use of small trifluoromethyl mo-
lecules as scaffolds.6 Recently, we reported7 the stereoselective
synthesis of different (E)-trifluoromethyl aldimines,8 obtained by
a solvent-free condensation reaction between trifluoroacetalde-
hyde ethyl hemiacetal9 and various amines, and the successive
transformation in their corresponding trifluoromethyl diaziridines
or oxaziridines by an aza- or an oxa-anion nucleophilic attack.10
Continuing our studies on the reactivity of trifluoromethyl
compounds, an aza-Henry11 reaction between different (E)-
trifluoromethyl aldimines (Schiff bases) and some nitro alkanes
was considered to obtain trifluoromethyl β-nitro amines,12 as
Table 1 Aza-Henry under different reaction conditions
Molar ratios
1a : 2a : catalyst
Yielda
(%)
Entry
Catalyst
Solvent
Time (h)
1
2
3
4
5
6
7
8
—
KF
—
1 : 5 : 0
24
24
24
24
24
24
24
24
2
2
2
2
2
—
—
—
—
—
—
—
i-PrOH
i-PrOH
—
THF
THF
—
—
—
—
—
1 : 5 : 0.4
1 : 5 : 0.4
1 : 5 : 0.4
1 : 5 : 1
1 : 5 : 1
1 : 5 : 1
1 : 5 : 0.5
1 : 5 : 1
1 : 5 : 1.3
1 : 5 : 0.5
1 : 2.5 : 0.5
1 : 5 : 0.25
1 : 5 : 0.25
KFb
KF
Et3N
Et3Nb
Et3N
(CO2H)2
ZrCl4
ZrCl4
ZrCl4
ZrCl4
ZrCl4
ZrCl4
—
9
65c
Trace
87c
50
10
11
12
13
14
Dipartimento di Chimica, Università degli Studi di Roma
“La Sapienza”, P.le Aldo Moro 5, I-00185 Roma, Italy.
—
—
—
20
20
E-mail: lucio.pellacani@uniroma1.it, stefania.fioravanti@uniroma1.it;
Fax: +39 06490631; Tel: +39 0649913673, +39 0649913098
†Electronic supplementary information (ESI) available: General pro-
18
a By 1H NMR spectra on the crude mixtures. b Performed at 70 °C.
c After purification on silica gel.
1
cedures, analytical and spectroscopic data, H and 13C NMR spectra of
all new compounds. See DOI: 10.1039/c2ob26397a
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem.

View Online
reactants were quantitatively recovered. Thus, inspired by our
recent results,16 ZrCl4 was chosen as a suitable Lewis acid cata-
lyst and the expected N-(1,1,1-trifluoro-3-nitropropan-2-yl)cyclo-
hexanamine (3a) was finally obtained under solvent-free reaction
conditions (entries 9 and 10).17 In order to optimize the ZrCl4-
catalyzed aza-Henry reaction, different molar ratios between the
catalyst and reagents were considered, the best reaction con-
ditions being those of entry 11. To test the specific role of ZrCl4,
other different Lewis acids were used as catalysts in the optimal
molar ratios (1a : 2a : catalyst = 1 : 5 : 0.5). However, after 24 h
neither the use of classical AlCl3, BF3·Et2O, nor the use of
Cu(I), Cu(II), and Ti(IV), employed in similar condensation reac-
tions,18 led to the expected product, except in traces (only for
TiCl4).
reaction temperature (−20 °C, 0 °C and 70 °C), but in all cases
no changes in diastereomeric ratios were observed. Except for 3c
and 3f, the syn/anti isomers were obtained as pure compounds
after separation by flash chromatography on silica gel. Moreover,
3b was converted by a selective reduction reaction of the nitro
group in the corresponding diamine 4b (Scheme 1). This last
compound can be further deprotected by a classical Pd catalyzed
hydrogenolysis of the benzylic residue.
The collected data show a strong influence of the fluorine on
the imine reactivity in the aza-Henry reaction. Contrary to what
one might expect, the inductive electron-withdrawing effect of
the CF3 group seems to be strong enough to decrease both
carbon electrophilicity and nitrogen basicity of the CvN double
bond.
Therefore, the ZrCl4-catalyzed aza-Henry reaction has been
extended to different (E)-trifluoromethyl aldimines and nitro
alkanes. As detected by 1H NMR spectra performed on the
crude mixtures, quantitative conversions were found in all cases
and then the obtained β-nitro α-trifluoromethyl amines were
purified on silica gel. The results are reported in Table 2.
In order to confirm our hypothesis, the reactivity of unfluori-
nated imines (E)-5a–e21 was tested in the aza-Henry conden-
sations with nitro alkanes 2a,b. While the use of ZrCl4 as a
catalyst led to exothermic reactions with probable complete poly-
merizations of the starting materials, the condensation performed
without the catalyst and solvent gave the expected unfluorinated
β-nitro amines 6a–d in good yields, under solvent-free con-
ditions. The results are reported in Table 3.
Working with unfluorinated substrates, while no differences
on the stereochemical outcome were observed, the reaction
pathway is completely different and still interesting. Probably,
the same imines act as both substrates and bases, generating
in situ the nitronate and activating itself by self-protonation, thus
confirming the effect of the trifluoromethyl group on the reactiv-
ity of compounds in which it is present.
As shown in Table 2, the aza-Henry reaction outcome seems
to be independent of the cyclic or linear nature of the R
groups,19 while it was deeply influenced by the nature of the
used nitro compound, showing to suffer from steric hindrance. In
fact, moving from nitromethane (entries 1, 4, 7, and 9) to
nitroethane (entries 2, 5, 8, and 10) and 1-nitropropane (entries 3
and 6) the reactions needed more time to occur and the corres-
ponding β-nitro α-trifluoromethyl amines were obtained in lower
yields. Moreover, when the reaction was performed with 2-nitro-
propane no condensation was observed and both reagents were
quantitatively recovered. In contrast, the stereochemical reaction
outcome is not influenced by the used nitro alkane, the major
product being the anti isomer20 in all cases. The syn/anti diaster-
eomeric ratios were determined by 1H NMR analysis on the
crude mixture. In order to improve the diastereoselectivity,
the aza-Henry reaction was performed on 1a by changing the
Starting from these data, a catalytic cycle to explain the
ZrCl4-catalyzed aza-Henry reaction pathway performed on
(E)-trifluoromethyl aldimines can be proposed (Scheme 2).
Zr(IV) coordinates both the imino nitrogen and the nitro alkane
oxygen,22 determining an increase of acidity of the nitro
Table 2 Synthesis of β-nitro α-trifluoromethyl amines
Scheme 1 Synthesis of 4b.
Table 3 Synthesis of β-nitro amines
Entry
1
a
R
2a
R′
3
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
a
b
c
a
b
c
H
Me
Et
H
Me
Et
a
b
c
d
e
f
g
h
2
87
82
79
84
80
75
86
77
18
24
2
18
24
2
b
Entry
2
R′
5a
R
6
Time (h)
Yieldb (%)
c
a
b
H
Me
1
2
3
4
a
b
a
b
H
Me
H
a
a
b
b
Me
Me
i-Bu
i-Bu
a
b
c
3
18
3
95
90
90
89
18
9
10
d
a
b
H
Me
i
j
2
18
83
78
Me
d
18
a Molar ratios 2 : 5 = 5 : 1. b After fast filtration through a plug filled with
silica gel.
a Molar ratios 1 : 2 : ZrCl4 = 1 : 5 : 0.5. b After purification on silica gel.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2012

View Online
N2-Benzyl-3,3,3-trifluoropropan-1,2-diamine (4b)
The title compound was synthesized modifying a reported pro-
cedure for the nitro group reduction reaction.25b Anhydrous
ammonium formate (310 mg, 5 mmol) and Pd/C 10% (95 mg)
were added, under an inert atmosphere (Ar), to a solution of 3b
(248 mg, 1 mmol) in anhydrous MeOH. The reaction mixture
was kept at reflux for 1.5 h after which it was filtered off to
remove the catalyst. The solvent was evaporated under vacuum
and 5 mL of water was added; the mixture was extracted three
times with Et2O. The collected organic layers were dried over
anhydrous Na2SO4 and the solvent evaporated under vacuum.
Pale yellow oil. Yield 65% (0.142 g). Purified by fast filtration
through a plug filled with silica gel using AcOEt as an eluent.
νmax cm−1 3491; 3393. 1H NMR (300 MHz, CDCl3) δ:
7.39–7.27 (m, 5H), 3.96 (dd, J = 62.6, 13.1 Hz, 2H), 3.11–2.92
(m, 1H), 2.97 (dd, J = 13.3, 3.6 Hz, 1H), 2.74 (dd, J = 13.0,
8.1 Hz, 1H), 1.83 (br, 3H). 13C NMR (75 MHz, CDCl3) δ:
139.4, 128.4 (2C), 128.1 (2C), 127.2, 126.6 (q, J = 284.5 Hz),
60.2 (q, J = 26.0 Hz), 51.7, 40.0. HRMS: m/z [M + H]+ calcd
for C10H14F3N2 219.1109, found 219.1105.
Scheme 2 Proposed catalytic cycle of the new aza-Henry reaction of
trifluoromethyl aldimines.
compound, that can be then deprotonated by a second molecule
of the trifluoromethyl aldimine. Finally, a favored intramolecular
nucleophilic attack followed by protonation leads to the for-
mation of fluorinated β-nitro amines 3.
N-(1-Nitropropan-2-yl)cyclohexanamine (6a)
(E)-Aldimine 5a (1 mmol) was stirred at room temperature
(3–18 h) with a five-fold excess of the nitro compound, under
solvent free conditions. After removal of the excess nitro com-
pound under vacuum, the crude mixture was purified through a
plug filled with silica gel using AcOEt as an eluent. Yellow-
brown oil. Yield 95% (0.177 g). νmax cm−1 3355; 1568. 1H
NMR (300 MHz, CDCl3) δ: 4.38–4.27 (m, 1H), 3.56–3.46 (m,
1H), 2.55–2.46 (m, 1H), 1.86–1.55 (m, 7H), 1.17 (d, J = 6.5 Hz,
3H), 1.33–0.99 (m, 5H). 13C NMR (75 MHz, CDCl3) δ: 79.8,
53.9, 51.8, 34.2, 33.7, 26.0, 24.8, 24.7, 17.0. HRMS: m/z
[M + H]+ calcd for C9H19N2O2 187.1447, found 187.1445.
In conclusion in this paper a zirconium tetrachloride catalyzed
aza-Henry reaction of (E)-trifluoromethyl aldimines is reported.
The new methodology here presented is strongly dependent on
the presence in the imines of the CF3 moiety that induces deep
modifications in the substrate reactivity. Recently, an elegant
work reported ZrCl4 as a suitable and efficient catalyst, compati-
ble with the CF3 group.23 The obtained trifluoromethyl β-nitro
amines are useful synthetic building blocks, due to the known
chemical versatility of the nitro group often called synthetic cha-
meleon,24 that easily undergoes reduction reactions,25 giving the
corresponding fluorinated 1,2-diamines,26 or Nef reaction,27 that
lead to valuable trifluoromethyl α-amino acids28 or ketones.29
Acknowledgements
We are grateful for financial support from the Università degli
Studi di Roma “La Sapienza”.
N-(1,1,1-Trifluoro-3-nitropropan-2-yl)cyclohexanamine (3a)
Notes and references
To a mixture of (E)-trifluoromethyl aldimine 1a (1 mmol) and
nitro compound 2a (5 mmol), ZrCl4 (0.5 mmol) was added. The
reaction was performed under solvent-free conditions and stirred
at room temperature (2–24 h). Then, after addition of water
(5 mL), the crude mixture was extracted three times with Et2O.
The collected organic layer was dried over anhydrous Na2SO4
and the solvent evaporated under vacuum. The crude mixture
was purified by flash chromatography on silica gel. Yellow-
brown oil. Yield 87% (0.209 g). Purified by fast filtration
through a plug filled with silica gel using AcOEt as an eluent.
νmax cm−1 3355; 1567. 1H NMR (CDCl3, 300 MHz) δ: 4.61 (dd,
J = 12.6, 4.2 Hz, 1H), 4.35 (dd, J = 12.6, 9.4 Hz, 1H),
4.14–4.01 (m, 1H), 2.71–2.63 (m, 1H), 1.89–1.48 (m, 5H),
1.35–0.99 (m, 6H). 13C NMR (75 MHz, CDCl3) δ: 125.2 (q, J =
284.5 Hz), 75.3, 55.7 (q, J = 29.1 Hz), 54.8, 34.1, 32.8, 25.9,
24.7, 24.4. HRMS: m/z [M + H]+ calcd for C9H16F3N2O2
241.1164, found 241.1161.
1 (a) Organofluorine Chemistry: Principles and Commercial Applications,
ed. R. E. Banks, B. E. Smart and J. C. Tatlow, Plenum, New York, 1994;
(b) Chemistry of Organic Fluorine Compounds II, ed. M. Hudlicky and
A. E. Pavlath, American Chemical Society, Washington, DC, 1995;
(c) P. Bravo, L. Bruché, M. Crucianelli, F. Viani and M. Zanda, ACS
Symp. Ser., 2000, 746, 98 (Asymmetric Fluoroorganic Chemistry);
(d) Organofluorine Compounds: Chemistry and Applications, ed.
T. Hiyama, Springer, New York, 2000; (e) V. P. Kukhar,
A. E. Sorochinsky and V. A. Soloshonok, Future Med. Chem., 2009, 1,
793; (f) N. Al-Maharik and D. O’Hagan, Aldrichimica Acta, 2011, 44,
65; (g) D. O’Hagan, J. Org. Chem., 2012, 77, 3689.
2 S. Purser, P. R. Moore, S. Swallow and V. Gouverneur, Chem. Soc. Rev.,
2008, 37, 320–330.
3 (a) Biomedicinal Aspects of Fluorine Chemistry, ed. R. Filler, Y. Kobaya-
shi and L. M. Yagupolskii, Elsevier, Amsterdam, 1993; (b) Biomedical
Frontiers of Fluorine Chemistry, ed. I. Ojima, J. R. McCarthy and
J. T. Welch, American Chemical Society, Washington, DC, 1996;
(c) J.-P. Bégué and D. Bonnet-Delpon, Chimie Bioorganique et Médici-
nale du Fluor, EDP sciences CNRS Editions, 2005; (d) K. Mueller,
C. Faeh and F. Diederich, Science, 2007, 317, 1881; (e) R. Filler and
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem.

View Online
R. Saha, Future Med. Chem., 2009, 1, 777; (f) T. Yamazaki, T. Taguchi
and I. Ojima, Fluorine in Medicinal Chemistry and Chemical Biology,
ed. I. Ojima, John Wiley & Sons, Ltd, Chichester, UK, 2009, pp. 3–46.
4 B. E. Smart, J. Fluorine Chem., 2001, 109, 3 and ref. therein.
5 (a) K. Mikami, Y. Itoh and M. Yamanaka, Chem. Rev., 2004, 104, 1;
(b) J.-A. Ma and D. Cahard, Chem. Rev., 2004, 104, 6119; (c) K. L. Kirk,
Org. Process Res. Dev., 2008, 12, 305.
6 M. Hideyuki, K. Kosuke, Y. Tetsuya, S. Takeshi and K. Yasuo, J. Fluor-
ine Chem., 2010, 131, 477.
7 L. Carroccia, S. Fioravanti, L. Pellacani and P. A. Tardella, Synthesis,
2010, 4096.
absence of any catalyst no reaction was observed and the reagents were
quantitatively recovered; while when ZrCl4 was used as a catalyst an
exothermic reaction occurs leading to a complex polymeric mixture.
20 The syn/anti nomenclature is used according to Masamune convention:
(a) S. Masamune, S. A. Ali, D. L. Snitman and D. S. Garvey, Angew.
Chem., 1980, 92, 573, (Angew. Chem., Int. Ed., 1980, 19, 557);
(b) S. Masamune, T. Kaiho and D. S. Garvey, J. Am. Chem. Soc., 1982,
104, 5521.
21 The unfluorinated imines (E)-4a–b were synthesized by a direct conden-
sation reaction between suitable aldehydes and cyclohexylamine using an
equimolar ratio, under solvent-free conditions. They were obtained as
only E isomers and used without further purification.
8 J.-P. Bégué, D. Bonnet-Delpon, B. Crousse and J. Legros, Chem. Soc.
Rev., 2005, 34, 562.
22 For
a
similar catalytic process see: (a) M. Johannsen and
9 Y. Gong and K. Kato, Curr. Org. Chem., 2004, 8, 1659.
10 L. Carroccia, S. Fioravanti, L. Pellacani and P. A. Tardella, Tetrahedron,
2011, 67, 5375.
11 (a) B. Westermann, Angew. Chem., 2003, 115, 161, (Angew. Chem., Int.
Ed., 2003, 42, 151); (b) E. Marqués-López, P. Merino, T. Tejero and
R. Herrera, Eur. J. Org. Chem., 2009, 2401.
K. A. Jørgensen, J. Chem. Soc., Perkin Trans. 2, 1997, 1183; (b) Ref.
18b.
23 B. Morandi and E. M. Carreira, Angew. Chem., 2011, 123, 9251, (Angew.
Chem., Int. Ed., 2011, 50, 9085).
24 G. Calderari and D. Seebach, Helv. Chim. Acta, 1985, 68, 1592.
25 (a) K. Prasad, X. Jiang, J. S. Slade, J. Clemens, O. Repič and
T. J. Blacklock, Adv. Synth. Catal., 2005, 347, 1769; (b) Y. Chi, L. Guo,
N. A. Kopf and S. H. Gellman, J. Am. Chem. Soc., 2008, 130, 5608.
26 D. Lucet, T. Le Gall and C. Mioskowski, Angew. Chem., 1998, 110,
2724, (Angew. Chem., Int. Ed., 1998, 37, 2580).
12 For
a different multi-step synthesis of fluorinated α-nitro amines:
V. Yu. Korotaev, A. Yu. Barkov, M. I. Kodess, I. B. Kutyashev,
P. A. Slepukhin and A. Ya. Zapevalov, Russ. Chem. Bull., Int. Ed., 2009,
58, 1886.
13 (a) Fluorine Containing Amino Acids: Synthesis and Properties, ed.
V. P. Kukhar and V. A. Soloshonok, Wiley, Chichester, UK, 1994;
(b) S. Fustero, J. F. Sanz-Cervera, J. Piera, M. Sanchez-Rosello, G. Chiva
and A. Simon-Fuentes, J. Fluorine Chem., 2004, 125, 621;
(c) J. L. Acena, A. Simon-Fuentes and S. Fustero, Curr. Org. Chem.,
2010, 14, 928.
14 The same fluorinated imines were able to deprotonate in situ ethyl nosyl-
oxycarbamate, acting as both base and substrate in aziridination reactions:
see ref. 10 and M. Barani, S. Fioravanti, M. A. Loreto, L. Pellacani and
P. A. Tardella, Tetrahedron, 1994, 50, 3829.
15 J. Hubner, J. Liebscher and M. Patzel, Tetrahedron, 2002, 58, 10485. To
the best of our knowledge only one recent paper reported a base catalyzed
aza-Henry reaction performed on fluorinated α,β-unsaturated ketimines:
F. Zhang, Z.-J. Liu and J.-T. Liu, Org. Biomol. Chem., 2011, 9, 3625.
16 S. Fioravanti, L. Pellacani and M. C. Vergari, Org. Biomol. Chem., 2012,
10, 524.
17 For very recent solvent-free Henry reactions, see: M. Fabris, M. Noè,
A. Perosa, M. Selva and R. Ballini, J. Org. Chem., 2012, 77, 1805.
18 (a) C. Gennari, I. Venturini, G. Gislon and G. Schimperna, Tetrahedron
Lett., 1987, 28, 227; (b) N. Nishiwaki, K. R. Knudsen, K. V. Gothelf and
K. A. Jørgensen, Angew. Chem., 2001, 113, 3080, (Angew. Chem., Int.
Ed., 2001, 40, 2992).
27 (a) E. Foresti, G. Palmieri, M. Petrini and R. Profeta, Org. Biomol.
Chem., 2003, 1, 4275; (b) R. Ballini and M. Petrini, Tetrahedron, 2004,
60, 1017.
28 (a) Fluorine Containing Amino Acids: Synthesis and Properties, ed.
V. P. Kukhar and V. A. Soloshonok, Wiley, New York, 1995;
(b) N. C. Yoder and K. Kumar, Chem. Soc. Rev., 2002, 31, 335;
(c) M. Zanda, New J. Chem., 2004, 28, 1401; (d) C. Jäckel and
B. Koksch, Eur. J. Org. Chem., 2005, 4483; (e) R. Smits,
C. D. Cadicamo, K. Burger and B. Koksch, Chem. Soc. Rev., 2008, 37,
1727; (f) D. Enders, K. Gottfried and G. Raabe, Adv. Synth. Catal., 2010,
352, 3147; (g) A. Ishii, M. Yasumoto, T. Yamazaki, K. Mogi and
Ta. Masuda, PCT Int. Appl., WO 2010026918 A1 20100311, 2010;
(h) T. Katagiri, Y. Katayama, M. Taeda, T. Ohshima, N. Iguchi and
K. Uneyama, J. Org. Chem., 2011, 76, 9305.
29 (a) M. W. Walter, R. M. Adlington, J. E. Baldwin, J. Chuhan and
C. J. Schofield, Tetrahedron Lett., 1995, 36, 7761; (b) M. W. Walter,
R. M. Adlington, J. E. Baldwin and C. J. Schofield, J. Org. Chem., 1998,
63, 5179; (c) J. Legros, D. Bouvet, B. Crousse, D. Bonnet-Delpon and
J. P. Bégué, Synthesis, 2000, 838; (d) R. P. Singh and J. M. Shreeve,
J. Org. Chem., 2000, 65, 3241; (e) G. Hughes, P. N. Devine, J. R. Naber,
P. D. O’Shea, B. S. Foster, D. J. McKay and R. P. Volante, Angew.
Chem., 2007, 119, 1871, (Angew. Chem., Int. Ed., 2007, 46, 1839);
(f) T. Shibata and S. Noritake, Jpn. Kokai Tokkyo Koho, JP 2010209007
A 20100924, 2010.
19 We tested the reactivity of another trifluoromethyl imine N-protected by
the p-methoxyphenyl (PMP) group. However reacting this imine in the
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2012