Synthesis of biologically relevant compounds by ruthenium porphyrin catalyzed amination of benzylic C-H bonds

Article abstract of DOI:10.1021/om500064d

Herein we report the catalytic activity of ruthenium porphyrin complexes to promote the amination of benzylic C-H bonds by aryl azides, yielding α- and β-amino esters. The catalytic methodology is also effective to synthesize two derivatives of methyl l-3-phenyllactate in order to convert one of them into the corresponding β-lactam. The catalytic experimental conditions have been optimized on the basis of a preliminary mechanistic investigation which underlines the pivotal role of the substrate concentration to maximize the reaction productivity.

Full text of DOI:10.1021/om500064d

Article
pubs.acs.org/Organometallics
Synthesis of Biologically Relevant Compounds by Ruthenium
Porphyrin Catalyzed Amination of Benzylic C−H Bonds
Paolo Zardi,† Alessandro Caselli,† Piero Macchi,‡ Francesco Ferretti,† and Emma Gallo*,†
†Department of Chemistry, University of Milan, Via Golgi 19, 20133 Milan, Italy
‡Department of Chemistry & Biochemistry, University of Berne, Freiestrasse 3, CH-3012 Berne, Switzerland
S
* Supporting Information
ABSTRACT: Herein we report the catalytic activity of ruthenium porphyrin
complexes to promote the amination of benzylic C−H bonds by aryl azides,
yielding α- and β-amino esters. The catalytic methodology is also effective to
synthesize two derivatives of methyl L-3-phenyllactate in order to convert one of
them into the corresponding β-lactam. The catalytic experimental conditions have
been optimized on the basis of a preliminary mechanistic investigation which
underlines the pivotal role of the substrate concentration to maximize the reaction
productivity.
Scheme 1. Synthesis of α- and β-Amino Esters
INTRODUCTION
■
The C−H amination of hydrocarbons catalyzed by metal
complexes is an efficient tool to synthesize high-value nitrogen-
containing compounds employing cheap starting materials.1−4
In order to respond to common requests for sustainable
chemistry, the scientific community is very interested in the
employment of organic azides (RN3) as nitrogen sources for
the synthesis of aza-containing molecules.5−12 The process
shows good atom efficiency and ecocompatibility due to the
formation of environmentally friendly molecular nitrogen as the
only stoichiometric byproduct. The extensive use of organic
azides as starting materials, up to now, has been largely
hampered by their intrinsic danger.7 However, among RN3
compounds, aryl azides (ArN3) show good chemical stability, as
the azide group conjugates well with the aromatic moiety. In
fact, Sigma-Aldrich has recently developed an efficient synthetic
method to obtain these compounds in bulky amounts using a
safe procedure.13 This could open new doors to the extensive
employment of aryl azides in different fields of synthetic
chemistry.
In view of the great importance of amino esters, not to
mention their role as precursors of other biological and
pharmaceutical compounds, a wide variety of catalytic
methods32−37 such as the N−H insertion of carbenes38−42
and reduction of β-enamino esters43−46 have been studied.
We describe herein the catalytic activity of ruthenium
porphyrins to synthesize α- and β-amino esters and the
conversion of the latter into β-lactams. In order to optimize the
reaction efficiency, a mechanistic study was also performed.
The nitrene transfer reaction is efficiently catalyzed by metal
porphyrin complexes,14−22 and in the past decade we have
extensively employed ruthenium23−26 and cobalt porphyr-
ins27−29 to promote the reaction between aryl azides and
activated sp3 C−H bonds.30 Even though metal porphyrins are
efficient catalysts for benzylic C−H aminations, the direct
nitrene transfer from an azide into a benzylic C−H bond placed
in a position α or β to an ester group has been less explored
(Scheme 1).16,31 This is due to the poor reactivity of electron-
deficient benzylic positions toward electrophilic metallonitrene
intermediates.
RESULTS AND DISCUSSION
■
We started studying the amination of methyl phenylacetate by
3,5-bis(trifluoromethyl)phenyl azide in the presence of different
metal porphyrin catalysts (Table 1).
As reported in Table 1, the aminated compound 1 was
formed in higher yields when the ruthenium porphyrin 2
(Table 1, run 1) was used instead of Co(TPP) (4; TPP =
Received: January 21, 2014
Published: April 24, 2014
© 2014 American Chemical Society
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Table 1. Amination of Methyl Phenylacetate by 3,5-
a
Bis(trifluoromethyl)phenyl Azide
b
c
run
catalyst
conversion (%)
t (h)
yield (%)
1
2
3
4
5
6
7
8
Ru(TPP)CO (2)
Ru(TPP)CO (2)
Ru(TPP)CO (2)
Ru(TPP)CO (2)
Ru(p-CF3TPP)CO (3)
Co(TPP) (4)
100
100
100
100
100
100
0
8
64
30
40
70
60
51
d
21
e
31
f
3
10
3
Mn(TPP)Cl (5)
Fe(TPP)Cl (6)
0
a
Reactions were run at 80 °C under nitrogen in 30 mL of benzene
with 1/10/50 cat./ArN3/benzylic substrate until complete aryl azide
b
conversion. The ArN3 conversion was monitored by IR spectroscopy
c
following the N3 absorbance decrease at 2116 cm−1. Measured by
NMR spectroscopy using 2,4-dinitrotoluene as the internal standard.
d
e
f
Run in 1,2-dichloroethane. Run in acetonitrile. Run in methyl
phenylacetate.
dianion of tetraphenylporphyrin) as catalyst (Table 1, run 6).
On the other hand, no azide conversion was observed in the
presence of Mn(TPP)Cl (5) and Fe(TPP)Cl (6) (Table 1,
runs 7 and 8, respectively). Shorter reaction times were
achieved by using methyl phenylacetate as the solvent (Table 1,
run 4). If the temperature of the reaction run in methyl
phenylacetate was increased from 80 to 100 °C, a further
decrease of the azide conversion time was observed. Methyl
(3,5-bis(trifluoromethyl)phenylamino)phenylacetate (1) was
obtained in only 1.5 h in 72% yield.
Figure 1. ORTEP plot of the molecular structure of methyl (3,5-
bis(trifluoromethyl)phenylamino)phenylacetate (1). The disorder of
the CF3 groups has been removed for the sake of clarity.
Compound 1 (Figure 1) crystallizes in space group P1 with
in 6 h, and compound 1 was isolated in 80% reaction yield (see
below).
̅
two independent molecules in the asymmetric unit and
therefore four molecules in the unit cell. The packing is quite
loose, in the absence of any strong intermolecular interaction,
and as a result, all the CF3 groups are rotationally disordered
about their ideal 3-fold axis. The purpose of this crystal
structure determination was mainly to have a reference for the
ligand used in coordination to ruthenium (see below).
Any attempt to recover this new complex in a pure form
failed due to the constant presence of traces of 1. Conversely,
when the reaction was catalyzed by RuII(p-CF3TPP)CO (3),
the purification of the crude product by flash chromatography
allowed the isolation of the bis-amido species RuIV(p-
CF3TPP)(ArNR)2 (Ar = 3,5-(CF3)2C6H3, R = CH(Ph)-
COOMe) (7) as purple crystals. Complex 7 was fully
characterized, and its molecular structure determined by
single-crystal X-ray diffraction is reported in Figure 2.
Complex 7 crystallizes in the space group C2/c. The unit cell
contains eight molecules, although of two nonequivalent kinds.
In fact, two different molecules of 7 are present, each sitting on
an inversion center, coinciding of course with the ruthenium
position. Therefore, the asymmetric unit contains two half-
molecules. The crystal packing is not very efficient, and
molecules of solvent (n-hexane and CH2Cl2) are cocrystallized.
CH2Cl2 is disordered over two positions; moreover, some
unexplained voids are found, compatible with additional
CH2Cl2 molecules, although no significant residual electron
density is calculated in these sites.
The TLC analyses of the crude of the reactions catalyzed by
Ru(TPP)CO in benzene (Table 1, run 1) and methyl
phenylacetate (Table 1, run 4) revealed the presence of
different ruthenium species at the end of the catalysis according
to the employed solvent. Ru(TPP)CO is the only ruthenium
complex observed when methyl phenylacetate is the reaction
solvent, while a new purple ruthenium species was formed in
addition to Ru(TPP)CO by running the reaction in benzene. If
in the latter case the catalytic azide concentration was doubled
(the Ru(TPP)CO/azide/methyl phenylacetate ratio of 1/10/
50 was replaced by 1/20/50), the aryl azide conversion was not
complete (80%), organic compound 1 was obtained in a low
yield (29%), and the new purple complex was the only
ruthenium species detectable by TLC in the catalytic mixture.
This last experiment indicated that the aryl azide/Ru(TPP)CO
ratio is fundamental to drive the reaction toward the formation
of the new complex when a low methyl phenylacetate
concentration in benzene is employed. Conversely, when the
reaction is performed in methyl phenylacetate as the reaction
solvent, Ru(TPP)CO was the principal ruthenium species in
the catalytic mixture also by using a Ru(TPP)CO/azide
catalytic ratio of 1/50. The aryl azide conversion was complete
The geometry, the conformation, and the main bonding
features of the two molecules of 7 are substantially identical.
The main difference is due to the torsion of meso-aryl groups,
which is very close to 90° (with respect to the porphyrin plane)
in the molecule of Ru1, whereas it is smaller in the molecule of
Ru2.
The average Ru−N bond distance of the porphyrin, 2.049(4)
Å, is quite in keeping with the statistics available from the
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Figure 2. ORTEP plot of the molecular structure of 7.
Scheme 2. Mechanistic Proposal for the Synthesis of 1
Cambridge Structural Database,47 2.052(1) Å. The coordina-
tion of the axial ligand is also quite similar to that of other
hexacoordinated metals in porphyrins. In both independent
molecules Ru−N is 1.944(5) Å, comparable to that of RuIV(p-
(NAr)2 (8)24,26 formed during the catalysis run at low substrate
concentrations. We suggest that the formation of 7 occurs by a
homolytic cleavage of the substrate benzylic C−H bond,
similarly to that already described for the synthesis of an
analogous bis-amido ruthenium(IV) complex.24,26 It should be
noted that complex 7 would never have formed if the
concentration of methyl phenylacetate was larger than 1.0 M.
To validate the hypothesis stated above, we prepared and
characterized complex 8 from the stoichiometric reaction of
Ru(p-CF3TPP)(CO) with ArN3 to employ it as a catalyst for
the synthesis of methyl (3,5-bis(trifluoromethyl)phenylamino)-
phenylacetate (1) (see the Experimental Section). The α-amino
ester 1 was obtained in 22 h at a 51% yield, indicating that
Ru(p-CF3TPP)(NAr)2 (8) is a less efficient catalyst than Ru(p-
CF3TPP)(CO) (3), which produced in 10 h a 60% yield of 1
(entry 5, Table 1). The analysis of the crude reaction product
revealed the presence of the inactive complex RuIV(p-
CF3TPP)(ArNR)2 (7), supporting the hypothesis that the
lower observed catalytic efficiency is due to the partial
transformation of 8 into 7.
48
CH3TPP)(p-ClC6H4NH)2 or RuIV(TPP)(3,5-(CF3)2C6H3N-
(C6H9)).24,26
In comparison with compound 1, the main difference is the
conformation adopted by the 3,5-(CF3)2C6H3 moiety, which is
antiperiplanar with respect to the acetate group (along the N−
Cα bond) in 1, whereas it is synclinal in 7. Moreover in 1, the
aryl ring and the acetate group lie on the same plane, but they
are ca. 48° inclined in 7. The most important change in bond
distances occurs for the N−Caryl bond, which is much longer in
7 (1.462(7) and 1.470(6) Å) than in 1 (1.375(3) and 1.376(3)
Å).
Complex 7 is a very air stable compound and does not show
any catalytic activity in the reaction between azide and methyl
phenylacetate. For this reason we hypothesize that complex 7 is
a deactivated catalyst which can be obtained by the partial
decomposition of the bis-imido derivatives Ru(p-CF3TPP)-
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Figure 3. Dependence of the reaction rate with respect to the methyl phenylacetate concentration.
In order to study the mechanism of the formation of 7, we
reacted the bis-imido complex 8 with an excess of methyl
phenylacetate (8/methyl phenylacetate 1/250) in benzene. We
observed the formation of the aminated compound 1 in
addition to the contemporary transformation of 8 into
unidentified ruthenium species. On the other hand, when a
benzene solution of 8 was refluxed in the presence of both the
aryl azide and the substrate, a TLC analysis of the reaction
mixture revealed the complete conversion of 8 into 7. These
data are in accord with those already observed for the allylic
amination of cyclohexene.24
The formation of an inactive bis-amido complex can also
explain the difference in reaction times reported in entries 1
and 4 (Table 1), respectively. The aryl azide conversion was
slower in benzene than in methyl phenylacetate due to a
decrease of the catalyst loading in solution as a consequence of
the deactivation process.
Taking into account our recent theoretical study on the
amination of allylic C−H bonds,49 we propose a similar
mechanism (Scheme 2) where a central role in the catalytic
cycle is played by the monoimido ruthenium(IV) complex C.
We suggest that complex A can lose molecular nitrogen,
forming the monoimido species Ru(TPP)(NAr)CO (C), which
can either be trapped by methyl phenylacetate to yield the
desired amino ester or be transformed into the bis-imido
derivative Ru(TPP)(NAr)2 (E), depending on the benzylic
substrate concentration.
This proposal is in accord with our experimental results
which indicate that better catalytic performances are achieved
by working in the presence of high benzylic substrate
concentrations. In this case the formation of bis-imido complex
E is limited, which in turn limits the decomposition of E into
the deactivated catalyst F (cycle 2, Scheme 2).
In order to investigate the influence of the substrate
concentration on the rate of the Ru(TPP)CO-catalyzed
reaction between methyl phenylacetate and 3,5-bis-
(trifluoromethyl)phenyl azide, we performed eight runs at 75
°C by employing different benzylic substrate concentrations
and a catalyst/azide ratio of 1/5 (Figure 3a). The azide
concentration was chosen in order to limit the formation of the
bis-imido derivatives (E) and the occurrence of cycle 2 of
Scheme 2. The measurements50 were executed in the 0.1−7.0
mol L−1 methyl phenylacetate concentration range, and the
azide consumption was followed by IR spectroscopy,
monitoring the decrease of the N3 absorbance at 2116 cm−1.
The reaction rate increased by increasing the methyl
phenylacetate concentration up to 0.6 mol L−1; then a substrate
inhibition was evident (Figure 3a).51 As clearly reported in
Figure 3b, the reaction rate was inversely proportional to the
methyl phenylacetate concentration in the 1.0−7.0 mol L−1
range.
The observed inhibition process could be due to a reversible
coordination of the substrate to the metal center. This
hypothesis was supported by an IR analysis of the reaction
between Ru(TPP)CO and an excess of methyl phenylacetate. A
shift of the CO absorbance from 1956 to 1948 cm−1 was
observed after the addition of methyl phenylacetate to a
benzene solution of Ru(TPP)CO (see the Supporting
Information for experimental details and IR spectra).52
The data reported above imply that the first step of the
mechanism could be the substitution of the coordinated
substrate (RH in Scheme 2) with aryl azide, yielding species A,
which can enter into the catalytic cycle 1 reported in Scheme 2.
Clearly, the rate of the whole catalytic process also depends on
the substitution reaction rate, which is determined by the
substrate concentration. All of these results point out that the
benzylic substrate plays a double role in the mechanism: it
reacts with the ruthenium monoimido complex C to form the
desired α-amino ester, and with the catalyst Ru(TPP)CO (A) it
yields complex B (Scheme 2). Although at high methyl
phenylacetate concentrations the formation of B is favored with
a resulting decrease in reaction rates, these experimental
conditions are necessary to reduce the formation of the
deactivated catalyst F by keeping active the catalytic cycle 1 of
Scheme 2. It should be noted that, when the occurrence of
cycle 2 is limited, the catalyst loading remains constant during
the reaction with a consequential improvement in the catalytic
efficiency. A more in-depth kinetic study will be performed to
better clarify all the kinetic aspects of the catalytic cycle.
Taking into account all the mechanistic information, we
studied the scope of the reaction by reacting methyl
phenylacetate with some other aryl azides and by investigating
the reactivity of methyl dihydrocinnamate as the benzylic
substrate (Table 2). In order to render the methodology
economically sustainable, in all runs reported in Table 2, the
substrate excess was recovered at the end of the reaction by
high-vacuum distillation.
Experimental results indicate that 3,5-bis(trifluoromethyl)-
phenyl azide is the most effective azide for the amination of
both methyl phenylacetate (Table 2, run 1) and methyl
dihydrocinnamate (Table 2, run 2). To optimize the synthetic
procedure, we decreased the catalyst loading from 2 to 1 mol %
in the synthesis of compound 1 (run 1, Table 2). After 23 h,
only 50% of the starting azide was consumed and 1 was formed
in 27% yield. We suggest that the decomposition of the catalyst
into the inactive species 7 is favored by employing these
experimental conditions.
The amination of methyl phenylacetate by other aryl azides
afforded the corresponding aminated compounds in a low yield
(Table 1, run 1, products 9−11). However, the reaction of the
same azides with methyl dihydrocinnamate only afforded traces
of the corresponding β-amino esters. As is reported in Table 2,
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The reaction between methyl L-3-phenyllactate, where the
hydroxy moiety is protected as acetoxy (Table 2, run 4) or
methoxy (Table 2, run 5) groups, and 3,5-bis(trifluoromethyl)-
phenyl azide yielded the corresponding aminated compounds
in moderate yields. The interest in these last two reactions
comes from the use of compounds 17 and 18 as precursors of
biologically relevant compounds such as β-lactams36 and 2-
oxazolidinones.54 Then we studied the conversion of
compound 18 into the corresponding β-lactam, which was
obtained as a single diasteroisomer in 30% yield (Scheme 3).
The stereochemistry of compound 19 was assigned by
comparing its NMR data with those reported in the literature
for a similar compound.55
Table 2. Synthesis of α- and β-Amino Esters Catalyzed by
Ru(TPP)CO (2)
a
Scheme 3. Conversion of β-Amino Ester 18 into the
Corresponding β-Lactam 19
a
Reactions were run under nitrogen in 8.0 mL of benzene at 80 °C
b
with 1/50/1000 2/ArN3/ester. Time required to complete the ArN3
c
d
It should be noted that 19, formed by a ring closure reaction
of the anti stereoisomer of 18, is the only recovered compound;
the β-lactam corresponding to the syn isomer was not detected
in the reaction mixture. Note that the syn/anti ratio of 1/1
implies that a maximum yield of 50% can be obtained with
respect to the anti isomer when 19 is the product. It is worth
noting that compound 19 was obtained in only four steps,
starting from the low-priced L-phenylalanine through to the
formation of methyl L-3-phenyllactate,56 which was protected as
the methoxy derivative56 and then transformed into 18 (see the
Supporting Information).
conversion. Isolated yields. Run in methyl phenylacetate at 100 °C;
e
1/50/250 2/ArN3/substrate.
compound 12a was obtained in a good yield but after a long
reaction time (Table 2, run 2) together with another purple
porphyrin complex that was detected by TLC analysis. This
new ruthenium complex 13 was isolated by performing the
synthesis of 12a using 8 as the catalyst. Analytic data for
complex 13 are very similar to those reported for 7 to indicate
an analogous bis-amido molecular structure (see the Support-
ing Information for details).
CONCLUSION
To optimize the synthesis of 12a, the amination was
performed by employing the ketene trimethylsilyl acetal of
methyl dihydrocinnamate as the substrate (Table 2, run 3). The
reaction time decreased from 10 h to 20 min, but in the
meantime a decrease of the reaction selectivity was registered.
The β-amino ester 12a was formed along with the isomer 12b
in the ratio 85/15 12a/12b. Considering that the formation of
compound 12b could be due to the uncatalyzed reaction
between the ketene trimethylsilyl acetal of methyl dihydro-
cinnamate and 3,5-bis(trifluoromethyl)phenyl azide,53 we
repeated the reaction in the absence of the ruthenium catalyst,
but after 2 h the IR analysis did not reveal any consumption of
the starting azide. The formation of the isomeric mixtures 14a/
14b, 15a/15b, and 16a/16b was also observed by running the
reaction in the presence of the three other aryl azides reported
in run 3 of Table 2. This experimental procedure allowed the
synthesis of β-amino esters derived from aryl azides bearing
EWG groups in short reaction times and without using a large
excess of the substrate (Table 2, run 3). Even if the
employment of the ketene silyl acetal decreased the reaction
selectivity, it is important to underline that the two obtained
isomers can easily be separated by flash chromatography.
Compounds 12−16 were obtained after desilylation with
TBAF; any attempt to isolate compounds derived from the
direct amination of the ketene trimethylsilyl acetal failed.
■
We have reported herein the ruthenium porphyrin catalyzed
synthesis of α- and β-amino esters starting from the appropriate
benzylic substrate and aryl azide. A preliminary mechanistic
investigation, performed to optimize catalytic experimental
conditions, revealed the presence of at least two interconnected
catalytic cycles. The predominance of one over the other
depends on the benzylic substrate (RH) concentration. When
the reaction is run at high RH concentrations (7.0 mol L−1), a
RuII(porphyrin)CO complex is the active catalyst (cycle 1 of
Scheme 2); conversely, by using low RH concentrations a bis-
imido RuVI(porphyrin)(NAr)2 complex is the active species
(cycle 2 of Scheme 2). This second cycle showed a minor
catalytic efficiency because Ru(porphyrin)(NAr)2 can be
transformed into the catalytically inactive bis-amido
RuIV(porphyrin)(ArNR)2 complex.
Mechanistic data indicated that the reaction productivity is
strongly related to the benzylic substrate concentration and, to
achieve satisfactory product yields, a high benzylic substrate
concentration is required. The benzylic substrate excess was
always recovered at the end of the reactions by high-vacuum
distillation to increase the sustainability of the methodology.
The reported catalytic method was also employed to synthesize
two derivatives of methyl L-3-phenyllactate in order to convert
them into the corresponding β-lactam.
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reaction solvent: 64% yield, method A; 80% yield, method B. For
complex 3 as the catalyst and benzene as the reaction solvent: 60%
yield, method A. For complex 4 as the catalyst and benzene as the
reaction solvent: 51% yield, method A. For complex 8 as the catalyst:
51% yield, method A. δH (300 MHz; CDCl3): 7.48−7.34 (5H, m, H
Ar), 7.15 (1H, s, H Ar), 6.90 (2H, s, H Ar), 5.48 (1H, br, NH), 5.09
(1H, s, CH(NHAr)), 3.76 (3H, s, OCH3). δC (75 MHz; CDCl3):
171.5 (CO), 146.5 (C Ar), 136.2 (C Ar), 132.6 (CF3, q, J = 32.7
Hz), 129.4 (CH Ar), 129.0 (CH Ar), 127.3 (CH Ar), 125.3 (C Ar),
121.7 (C Ar), 112.8 (CH Ar), 111.3 (CH Ar), 60.3 (CH), 53.3
(OCH3). δF (282 MHz; CDCl3): −63.62 (CF3). HRMS ESI: (M +
H)+ calcd for C17H14NO2F6 378.0923, found 378.0927. IR (ATR):
3377 (νN−H), 1733 cm−1 (νCO). X-ray-quality crystals were obtained
by slow evaporation of a pentane solution of compound 1 at room
temperature.
Synthesis of Complex 7. A benzene (30.0 mL) solution of Ru(p-
CF3TPP)CO (3; 45.8 mg, 5.2 × 10−2 mmol), 3,5-bis(trifluoromethyl)-
phenyl azide (141.1 mg, 5.5 × 10−1 mmol), and methyl phenylacetate
(384.0 mg, 2.6 mmol) was refluxed until the aryl azide was completely
consumed (the reaction was monitored by IR spectroscopy, νNN
2116 cm−1). The solvent was evaporated to dryness and the residue
purified by flash chromatography (silica gel, n-hexane/dichloro-
methane 7/3) in 75% yield. The solid was dissolved in pentane, and
the solution was to slowly concentrate dat room temperature to give
X-ray-quality crystals. δH (300 MHz, C6D6, 338 K): 8.40 (8H, s, Hβ),
8.04 (8H, br, H1), 7.75 (8H, d, J = 7.7 Hz, H2), 6.93 (2H, s, H3), 6.30
(2H, m, H4), 6.11 (4H, m, H5), 4.18 (4H, m, H6), 4.11 (2H, s, H7),
2.58 (3H, s, OCH3), 2.52 (3H, s, OCH3), 1.88 (2H, m, H8), −0.88 (s,
2H, H9). δC (75 MHz, C6D6, 338 K): 162.9 (CO), 158.6 (C), 145.5
(C), 144.0 (C), 134.1 (CH Ar), 132.9 (CHβ), 131.9 (C), 131.1 (CF3
porphyrin), 127.4 (CH Ar), 124.1 (CH Ar), 121.9 (CH Ar), 117.3
(CH Ar), 80.2 (CH), 51.07 (OCH3), 51.98 (OCH3), the aryl CF3
signals and three quaternary carbon signals were not detected. δF (282
MHz, C6D6, 338 K): −62.01 (12F, CF3 porphyrin), −62.49 (6F, CF3
Ar), −63.07 (6F, CF3 Ar). UV−vis (CH2Cl2): λmax (log ε) 419 (5.20),
524 (4.53), 553 nm (4.36) sh. IR (ATR): 1744 (νCO), 1014 cm−1
(oxidation marker band). MS (FAB+): m/z 1362 [M − 376(R-N-
Ar)]+.
EXPERIMENTAL SECTION
■
General Conditions. All reactions were carried out under a
nitrogen atmosphere employing standard Schlenk techniques and
vacuum-line manipulations. Benzene was dried with an M. Braun SPS-
800 solvent purification system, while 1,2-dichloroethane and
acetonitrile were purified by distillation under nitrogen over CaH2.
Reagents. Organic azides,57 ketene silyl acetal,58 methyl L-3-
phenyllactate derivatives,56 TPPH2,59 p-CF3TPPH2,59 Ru(TPP)CO
(2),60 Ru(p-CF3TPP)CO) (3),60 and Co(TPP) (4)61 were synthe-
sized by methods reported in the literature or using minor
modifications of them.52 Methyl phenylacetate was distilled prior to
use under nitrogen. Complexes 5 and 6 together with all the other
starting materials are commercial products and were used as received.
Instruments. NMR spectra were recorded at 300 K (unless
otherwise specified) operating either at 300 MHz for 1H, 75 MHz for
13C and 282 MHz for 19F or at 400 MHz for 1H and 100 MHz for 13C.
1
Chemical shifts (ppm) are reported relative to TMS. The H NMR
signals of the compounds described in the following have been
assigned by COSY and NOESY techniques. Assignments of
resonances in 13C NMR were made by using the APT pulse sequence
and HSQC and HMBC techniques. GC-MS analyses were performed
on an instrument equipped with a capillary column (30 m × 0.25 mm
× 0.25 μm film thickness). Infrared spectra, UV/vis spectra, and mass
spectra were recorded in the analytical laboratories of Milan
University.
General Procedures for Catalytic Reactions. The catalytic
reactions were monitored by IR spectroscopy by measuring the
characteristic N3 absorbance in the range 2095−2130 cm−1. The
reaction was considered complete when the absorbance value of the
azide was below 0.01 (by using a 0.1 mm thick cell). 1H NMR analysis
was performed using 2,4-dinitrotoluene as the internal standard.
Method A. Aryl azide (6.1 × 10−1 mmol) was added to a suspension
of the catalyst (6.0 × 10−2 mmol) and substrate (3.0 mmol) in the
desired solvent (30.0 mL). The resulting mixture was heated to 80 °C
by using a preheated oil bath until the complete consumption of the
azide. The solvent was evaporated to dryness and the residue analyzed
1
by H NMR spectroscopy.
Method B. Aryl azide (5.0 × 10−1 mmol) was added to a methyl
phenylacetate (10.0 mL) suspension of Ru(TPP)CO (7.4 mg, 1.0 ×
10−2 mmol). The resulting mixture was heated to 100 °C using a
preheated oil bath until the complete consumption of the azide. The
solvent was evaporated to dryness and purified by flash chromatog-
raphy (silica gel, gradient elution with n-hexane/ethyl acetate).
Method C. Aryl azide (1.0 × 10−1 mmol) was added to a benzene
(7.0 mL) suspension of Ru(TPP)CO (7.4 mg, 1.0 × 10−2 mmol) and
substrate (10.0 mmol). The resulting mixture was refluxed using a
preheated oil bath until the complete consumption of the azide.
Benzene was evaporated to dryness, and the benzylic substrate excess
was recovered by high-vacuum distillation (0.035 mmHg at 80 °C).
The crude was purified by flash chromatography (silica gel, gradient
elution with n-hexane/ethyl acetate).
Synthesis of Complex 8. 3,5-Bis(trifluoromethyl)phenyl azide
(42.0 mg, 0.165 mmol) was added to a benzene (30 mL) suspension
of Ru(p-CF3TPP)CO (3; 41.0 mg, 4.0 × 10−2 mmol). The resulting
dark mixture was refluxed for 5 h until the complete consumption of 3
(TLC, n-hexane/CH2Cl2 7/3). The solvent was evaporated to dryness,
and n-hexane (20 mL) was added. The dark violet solid that
precipitated was collected by filtration and dried under vacuum (29.2
mg, 50%). δH (300 MHz, C6D6): 8.70 (8H, s, Hβ), 7.98 (8H, d, J = 7.8
Hz, H Ar porphyrin), 7.76 (8H, d, J = 8.0 Hz, H Ar porphyrin), 6.50
(2H, s, H Ar), 2.76 (4H, s, H Ar). δC (75 MHz, C6D6): 151.6 (C),
144.9 (C), 142.4 (C), 134.4 (CH Ar), 132.2 (CHβ), 131.7 (CF3),
129.9 (CF3), 124.4 (C), 122.6 (C), 118.3 (CH), 117.8 (CH). δF (282
MHz, C6D6): −61.67 (12F, s, CF3 porphyrin), −63.46 (12F, s, CF3
Ar). UV−vis (CH2Cl2): λmax (log ε) 359 (4.63), 419 (5.24), 524
(3.97), 590 nm (3.75). IR (ATR): 1014 cm−1 (oxidation marker
band), 884 cm−1 (imido band). MS (FAB+): m/z 1440 [M]+.
Synthesis of Methyl (4-(Trifluoromethyl)phenylamino)-
phenylacetate (9).62 Yield: 26% (method B). Analytical data are
in accord with those reported in the literature.
Synthesis of Methyl (4-Nitrophenylamino)phenylacetate
(10).63 Yield: 32% (method B). Analytical data are in accord with
those reported in the literature.
Synthesis of Methyl (4-tert-Butylphenylamino)phenyl-
acetate (11).64 Yield: 20% (method B). Analytical data are in accord
with those reported in the literature.
Synthesis of Methyl 3-(3,5-Bis(trifluoromethyl)phenyl-
amino)-3-phenylpropanoate (12a). Yield: 85% (method C, methyl
dihydrocinnamate was employed as the substrate), 77% (method D,
methyl dihydrocinnamate was employed as the substrate), 65%
(method E). δH (300 MHz, CDCl3): 7.38−7.27 (5H, m, H Ar), 7.12
(1H, s, H Ar), 6.90 (2H, s, H Ar), 5.17 (1H, br, NH), 4.85 (1H, dd, J
= 7.7 Hz, J = 5.3 Hz, CH(NHAr)), 3.67 (3H, s, OCH3), 2.90 (1H, dd,
Method D. The experimental procedure was identical to that
described in method C except for the azide amount (5.0 × 10−1
mmol).
Method E. Aryl azide (5.0 × 10−1 mmol) was added to a benzene
(10.0 mL) suspension of Ru(TPP)CO (7.4 mg, 1.0 × 10−2 mmol) and
ketene silyl acetal (591.0 mg, 2.5 mmol). The resulting mixture was
refluxed using a preheated oil bath until the complete consumption of
the azide, and then the solvent was evaporated to dryness. THF (25.0
mL) was added to the residue, and the resulting solution was placed in
an ice bath before adding a THF solution of tetra-n-butylammonium
fluoride (TBAF) (1.0 mol L−1, 3.0 mL). The solution was stirred for
15 min at 0 °C, poured into a saturated aqueous NH4Cl solution
(200.0 mL), and extracted with AcOEt (50.0 mL × 3), the extracts
were dried with Na2SO4, and the solvent was evaporated to dryness.
The crude product was then purified by flash chromatography (silica
gel, gradient elution with n-hexane/ethyl acetate).
Synthesis of Methyl (3,5-Bis(trifluoromethyl)phenylamino)-
phenylacetate (1). For complex 2 as the catalyst and benzene as the
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J = 15.2, 5.2 Hz, CHH), 2.82 (1H, dd, J = 15.2, 7.8 Hz, CHH). δC (75
MHz, CDCl3): 171.4 (CO), 147.5 (C Ar), 140.6 (C Ar), 132.5
(CF3, q, J = 32.9 Hz), 129.3 (CH Ar), 128.2 (CH Ar), 126.2 (CH Ar),
125.4 (C Ar), 121.8 (C Ar), 113.0 (CH Ar), 111.0 (CH Ar), 54.9
(CH), 52.2 (OCH3), 42.3 (CH2). δF (282 MHz, CDCl3): −63.58
(CF3). IR (ATR): 3396 (νN−H), 1727 cm−1 (νCO). HRMS ESI: (M +
H)+ calcd for C18H16NO2F6 392.1080, found 392.1074.
(CH Ar), 112.3 (CH Ar), 54.5 (CH), 52.2 (OCH3), 42.1 (CH2).
HRMS ESI: (M + H)+ calcd for C16H17N2O4 301.1183, found
301.1187.
Synthesis of Methyl 2-(4-Nitrophenylamino)-3-phenylpro-
panoate (15b). Yield: 21% (method E). δH (300 MHz, CDCl3): 8.07
(2H, d, J = 9.2 Hz, H Ar), 7.33−7.22 (3H, m, H Ar), 7.16−7.09 (2H,
m, H Ar), 6.52 (2H, d, J = 9.2 Hz, H Ar), 4.97 (1H, d, J = 8.0 Hz,
NH), 4.47 (1H, dt, J = 8.0, 6.0 Hz, CH(NHAr)), 3.74 (3H, s, OCH3),
3.23 (1H, dd, J = 13.8, 6.0 Hz, CHH), 3.14 (1H, dd, J = 13.8, 6.2 Hz,
CHH). δC (75 MHz, CDCl3): 172.2 (CO), 151.6 (C Ar), 139.1 (C
Ar), 135.4 (C Ar), 129.3 (CH Ar), 128.9 (CH Ar), 127.6 (CH Ar),
126.5 (CH Ar), 112.0 (CH Ar), 56.9 (CH), 52.7 (OCH3), 38.3
(CH2). HRMS ESI: (M + H)+ calcd for C16H17N2O4 301.1183, found
301.1182.
Synthesis of Methyl 3-(3,5-Dichlorophenylamino)-3-phenyl-
propanoate (16a). Yield: 65% (method E). δH (400 MHz, CDCl3)
7.45−7.22 (5H, m, H Ar), 6.64 (1H, br s, H Ar), 6.43 (2H, d, J = 1.6
Hz, H Ar), 4.78 (2H, m, CH(NHAr) and NH), 3.66 (3H, s, OCH3),
2.85 (1H, dd, J = 15.1, 5.3 Hz, CHH), 2.85 (1H, dd, J = 15.1, 5.3 Hz,
CHH), 2.78 (1H, dd, J = 15.1, 7.8 Hz, CHH). δC (100 MHz, CDCl3)
171.4 (CO), 148.5 (C Ar), 141.0 (C Ar), 135.5 (C Ar), 129.1 (CH
Ar), 128.0 (CH Ar), 126.2 (CH Ar), 117.7 (CH Ar), 112.0 (CH Ar),
54.7 (CH), 52.1 (OCH3), 42.4 (CH2). HRMS ESI: (M + H)+ calcd
for C16H16NO2Cl2 324.0553, found 324.0549.
Synthesis of Methyl 2-(3,5-Dichlorophenylamino)-3-phenyl-
propanoate (16b). Yield: 8% (method E). δH (400 MHz, CDCl3):
7.34−7.23 (3H, m, H Ar), 7.13 (2H, d, J = 6.8 Hz, H Ar), 6.70 (1H,
pst, H Ar), 6.43 (2H, d, J = 1.6 Hz, H Ar), 4.30 (2H, m, CH(NHAr)
and NH), 3.72 (3H, s, OCH3), 3.17 (1H, dd, J = 13.7, 5.4 Hz, CHH),
3.08 (1H, dd, J = 13.7, 5.9 Hz, CHH). δC (75 MHz, CDCl3): 172.8
(CO), 148.1 (C Ar), 135.82 (C Ar), 135.76 (C Ar), 129.4 (CH Ar),
128.8 (CH Ar), 127.4 (CH Ar), 118.3 (CH Ar), 111.8 (CH Ar), 57.3
(CH), 52.5 (OCH3), 38.5 (CH2). HRMS ESI: (M + H)+ calcd for
C16H16NO2Cl2 324.0553, found 324.0555.
Synthesis of (2S)-Methyl 2-Acetoxy-3-(3,5-bis(trifluoro-
methyl)phenylamino)-3-phenylpropanoate (17). Combined
yield of both syn and anti isomers: 35% (syn/anti 20/80, method
D, (2S)-methyl 2-acetoxy-3-phenylpropanoate employed as the
substrate). Syn/anti assignment was performed on the basis of
chemical shifts and coupling constant trends reported in the
literature.62 δH (400 MHz; CDCl3): major isomer (anti) 7.38−7.30
(5H, m, H Ar), 7.15 (1H, s, H Ar), 6.91 (2H, s, H Ar), 5.35 (1H, d, J =
4.9 Hz, CH(OAc)), 5.20 (1H, m, NH), 4.95 (1H, br, CH(NHAr)),
3.64 (3H, s, OCH3), 2.15 (3H, s, CH3 acetoxy); minor isomer (syn)
7.38−7.30 (5H, m, H Ar), 7.15 (1H, s, H Ar), 6.91 (2H, s, H Ar), 5.41
(1H, d, J = 2.6 Hz, CH(OAc)), 5.16−5.05 (2H, m, NH and
CH(NHAr)), 3.75 (3H, s, OCH3), 2.11 (3H, s, CH3 acetoxy). δC (100
MHz, CDCl3): major isomer (anti) 170.2 (CO acetoxy), 168.4
(CO methyl ester), 147.1 (C Ar), 136.8 (C Ar), 136.1 (C Ar), 132.6
(CF3, q, J = 33.1 Hz), 129.1 (CH Ar), 127.2 (CH Ar), 126.8 (CH Ar),
124.9 (C Ar), 122.2 (C Ar), 113.0 (CH Ar), 111.4 (CH Ar), 74.7
(CH(OAc)), 58.4 (CH(NHAr)), 52.6 (OCH3 methoxy), 20.7 (CH3
acetoxy); minor isomer (syn) 169.7 (CO acetoxy), 168.4 (CO
methyl ester), 147.0 (C Ar), 136.8 (C Ar), 136.1 (C Ar), 132.6 (CF3,
q, J = 33.1 Hz), 129.2 (CH Ar), 128.9 (CH Ar), 128.7 (CH Ar), 124.9
(C Ar), 122.2 (C Ar), 113.0 (CH Ar), 111.4 (CH Ar), 75.3
(CH(OAc)), 58.0 (CH(NHAr)), 53.1 (OCH3 methoxy), 20.5 (CH3
acetoxy). δF (282 MHz, CDCl3): −63.24 (CF3 minor isomer), −63.25
(CF3 major isomer). HRMS ESI: (M + H)+ calcd for C20H18NO4F6
450.1135, found 450.1137.
Synthesis of Methyl 2-(3,5-Bis(trifluoromethyl)phenyl-
amino)-3-phenylpropanoate (12b). Yield: 12% (method E). δH
(300 MHz, CDCl3): 7.35−7.23 (3H, m, H Ar), 7.20−7.12 (3H, m, H
Ar), 6.88 (2H, s, H Ar), 4.63 (1H, br, NH), 4.40 (1H, t, J = 5.3 Hz,
CH(NHAr)), 3.74 (3H, s, OCH3), 3.21 (1H, dd, J = 13.7, 5.6 Hz,
CHH), 3.11 (1H, dd, J = 13.7, 5.6 Hz, CHH. δC (75 MHz, CDCl3):
172.7 (CO), 147.3 (C Ar), 135.7 (C Ar), 132.7 (CF3, q, J = 32.8
Hz), 129.4 (CH Ar), 128.9 (CH Ar), 127.6 (CH Ar), 125.4 (C Ar),
121.7 (C Ar), 112.7 (CH Ar), 111.5 (CH Ar), 57.4 (CH), 52.6
(OCH3), 38.7 (CH2). δF (282 MHz, CDCl3): −63.54 (CF3). HRMS
ESI: (M + H)+ calcd for C18H16NO2F6 392.1080, found 392.1074.
Synthesis of Complex 13. 3,5-Bis(trifluoromethyl)phenyl azide
(814.0 mg, 3.2 mmol) was added to a benzene (30 mL) solution of 8
(90.7 mg, 6.3 × 10−2 mmol) and methyl dihydrocinnamate (2.12 g, 13
mmol). The resulting solution was refluxed until the aryl azide was
completely consumed (the reaction was monitored by IR spectrosco-
py, νNN 2116 cm−1). The mixture was concentrated, and methyl
dihydrocinnamate was removed by high-vacuum distillation. The
residue was purified by flash chromatography (silica gel, n-hexane/
AcOEt 50/1) (30% yield). δH (400 MHz, C6D6, 343 K): 8.43 (8H, m,
Hβ), 8.07 (8H, m, H1), 7.75 (8H, d, J = 7.8 Hz, H2), 6.97 (2H, s, H3),
6.43 (2H, m, H4), 6.20 (4H, m, H5), 4.07 (4H, t, J = 7.6 Hz, H6), 3.00
(1H, s, H7), 2.95 (1H, s, H7), 2.69 (1H, s, OCH3), 1.89 (1H, s, H8),
1.86 (1H, s, H8), 0.49 (2H, m, H9), −0.64 (2H, m, H10), −1.72 (2H, d,
J = 15.0 Hz, H11). δC (75 MHz, C6D6, 343 K): 167.7 (CO), 157.5
(C Ar), 157.3 (C Ar), 145.1 (C Ar), 144.0 (C Ar), 134.4 (CH Ar),
133.3 (CH Ar), 133.0 (C Ar), 131.1 (CF3), 127.3 (CH Ar), 126.8
(CH Ar), 124.2 (CH Ar), 122.1 (CH Ar), 119.2 (CH Ar), 117.6 (CH
Ar), 75.2 (CH), 50.8 (OCH3), 31.7 (CH2), one CF3 signal and three
quaternary carbon signals were not detected. δF (282 MHz, C6D6, 343
K): −62.31 (12F, s, CF3 porphyrin), −62.81 (12F, s, CF3 Ar), −63.53
(12F, s, CF3 Ar). UV−vis (CH2Cl2): λmax (log ε) 419 (5.11), 521
(4.32), 551 nm (4.20) sh. IR (ATR): 1740 (νCO), 1012 cm−1
(oxidation marker band). MS (FAB+): m/z 1376 [M − 390 (R-N-
Ar)]+.
Synthesis of Methyl 3-(4-(Trifluoromethyl)phenylamino)-3-
phenylpropanoate (14a). Yield: 38% (method E). δH (400 MHz,
CDCl3): 7.39−7.24 (7H, m, H Ar), 6.58 (2H, d, J = 8.4 Hz, H Ar),
4.86 (1H, m, CH(NHAr)), 3.66 (3H, s, OCH3), 2.85 (2H, m, CH2),
NH signal not detected. δC (100 MHz, CDCl3): 171.5 (CO), 149.3
(C Ar), 141.3 (C Ar), 129.1 (CH Ar), 128.0 (CH Ar), 126.7 (CH Ar),
126.3 (CH Ar), 123.6 (C Ar), 119.7 (CF3, q, J = 32.0 Hz), 113.1 (CH
Ar), 54.8 (CH), 52.1 (OCH3), 42.5 (CH2). δF (282 MHz, CDCl3):
−61.48 (CF3). HRMS ESI: (M + H)+ calcd for C17H17NO2F3
324.1206, found 324.1210..
Synthesis of Methyl 3-(4-(Trifluoromethyl)phenylamino)-3-
phenylpropanoate (14b). Yield: 14% (method E). δH (300 MHz,
CDCl3): 7.40 (2H, d, J = 8.5 Hz, H Ar), 7.29 (3H, m, H Ar), 7.14 (2H,
m, H Ar), 6.60 (2H, d, J = 8.5 Hz, H Ar), 4.41 (1H, t, J = 6.1 Hz, CH),
3.71 (3H, s, OCH3), 3.11 (1H, dd, J = 13.7, 6.3 Hz, CHH), (1H, dd, J
= 13.7, 5.9 Hz, CHH), NH signal was not detected. δC (75 MHz,
CDCl3): 173.0 (CO), 149.0 (C Ar), 136.0 (C Ar), 129.4 (CH Ar),
128.8 (CH Ar), 127.4 (CH Ar), 126.9 (CH Ar), 123.1 (C Ar), 120.1
(CF3, q, J = 32.7 Hz), 112.8 (CH Ar), 57.2 (CH), 52.4 (OCH3), 38.5
(CH2). δF (282 MHz, CDCl3): −61.53 (CF3). HRMS ESI: (M + H)+
calcd for C17H17NO2F3 324.1206, found 324.1211.
Synthesis of (2S)-Methyl 2-Methoxy-3-(3,5-bis(trifluoro-
methyl)phenylamino)-3-phenylpropanoate (18). Combined
yield of both syn and anti isomers 53% (syn/anti = 45:55, method
D, (2S)-methyl 2-methoxy-3-phenylpropanoate employed as the
substrate). Syn/anti assignment was done on the basis of chemical
shift and coupling constants trends reported in the literature.62 δH
(300 MHz; CDCl3): major isomer (anti) 7.37−7.27 (5H, m, H Ar),
7.11 (1H, s, H Ar), 6.91 (2H, s, H Ar), 5.37 (1H, d, J = 7.3 Hz, NH),
4.85 (1H, m, CH(NHAr)), 4.20 (1H, d, J = 4.7 Hz, CH(OMe)), 3.62
(3H, s, OCH3 ester), 3.48 (3H, s, OCH3 ether); minor isomer (syn)
Synthesis of Methyl 3-(4-Nitrophenylamino)-3-phenylpro-
panoate (15a). Yield: 55% (method E). δH (300 MHz, CDCl3): 8.00
(2H, d, J = 9.1 Hz, H Ar), 7.38−7.24 (5H, m, H Ar), 6.51 (2H, d, J =
9.1 Hz, H Ar), 5.63 (1H, d, J = 6.5 Hz, NH), 4.92 (1H, dd, J = 12.7,
6.7 Hz, CH(NHAr)), 3.65 (3H, s, OCH3), 2.98−2.79 (2H, m, CH2).
δC (75 MHz, CDCl3): 171.3 (CO), 152.2 (C Ar), 140.5 (C Ar),
138.6 (C Ar), 129.2 (CH Ar), 128.2 (CH Ar), 126.3 (CH Ar), 126.1
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7.37−7.27 (5H, m, H Ar), 7.09 (1H, s, H Ar), 6.87 (2H, s, H Ar), 5.27
(1H, d, J = 7.6 Hz, NH), 4.85 (1H, m, CH(NHAr)), 4.05 (1H, d, J =
3.0 Hz, CH(OMe)), 3.75 (3H, s, OCH3 ester), 3.36 (3H, s, OCH3
ether). δC (75 MHz, CDCl3): major isomer (anti) 170.8 (CO),
147.4 (C Ar), 136.6 (C Ar), 132.4 (CF3, q, J = 32.7 Hz), 128.9 (CH
Ar), 128.6 (CH Ar), 127.3 (CH Ar), 125.4 (C Ar), 121.8 (C Ar),
113.0 (CH Ar), 110.9 (CH Ar), 83.2 (CH(OMe)), 59.3 (OCH3
ether), 59.1 (CH(NHAr)), 52.1 (OCH3 ester); minor isomer (syn)
170.2 (CO), 147.5 (C Ar), 138.2 (C Ar), 132.4 (CF3, q, J = 32.7
Hz), 129.0 (CH Ar), 128.3 (CH Ar), 127.1 (CH Ar), 125.4 (C Ar),
121.8 (C Ar), 113.0 (CH Ar), 110.9 (CH Ar), 83.7 (CH(OMe), 59.6
(OCH3 ether), 59.1 (CH(NHAr)), 52.5 (OCH3 ester). δF (282 MHz,
CDCl3): −63.59 (CF3). HRMS ESI: (M + H)+ calcd for C19H18NO3F6
422.1185, found 422.1181.
Synthesis of (3S)-3-Methoxy-4-phenyl-1-(3,5-bis(trifluoro-
methyl))phenylazetidin-2-one (19). Compound 19 was obtained
from compound 18 (189 mg, 4.5 × 10−1 mmol) by using a reported
procedure (30% yield).36 Only one diastereoisomer was formed. δH
(300 MHz; CDCl3): 7.70 (2H, s, H Ar), 7.55 (1H, s, H Ar), 7.44−7.30
(5H, m, H Ar), 4.99 (1H, d, J = 1.9 Hz, CH(Ph)), 4.53 (1H, d, J = 1.9
Hz, CH(OMe)), 3.60 (3H, s, OCH3 methoxy). δC (75 MHz, CDCl3):
164.8 (CO), 138.5 (C Ar), 135.0 (C Ar), 132.8 (CF3, q, J = 33.7
Hz), 129.8 (CH Ar), 129.6 (CH Ar), 126.1 (CH Ar), 124.8 (C Ar),
121.1 (C Ar), 117.7 (CH Ar), 117.3 (CH Ar), 91.8 (CH(OMe)), 64.1
(CH(Ph)), 58.6 (OCH3 methoxy). δF (282 MHz, CDCl3): −63.53
(CF3). HRMS ESI: (M + H)+ calcd for C18H14NO2F6 390.0923, found
390.0926.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Figures giving NMR, UV−vis, IR, and GC-MS spectra of
isolated compounds and CIF files and tables giving crystallo-
graphic data for 1 and 7. This material is available free of charge
via the Internet at http://pubs.acs.org.
(31) Lu, H.; Hu, Y.; Jiang, H.; Wojtas, L.; Zhang, X. P. Org. Lett.
AUTHOR INFORMATION
Corresponding Author
*E-mail for E.G.: emma.gallo@unimi.it.
Notes
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2012, 14, 5158−5161.
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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We are grateful for financial support from the Programmi di
Ricerca Scientifica di Rilevante Interesse Nazionale (MIUR),
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