Synthesis of α-Amidoketones from Vinyl Esters via a Catalytic/Thermal Cascade Reaction

Article abstract of DOI:10.1021/acs.joc.5b02851

A straightforward, modular, and atom-efficient method is reported for the synthesis of α-amidoketones from vinyl esters via a cascade reaction including hydroformylation, condensation with a primary amine, and a rearrangement step giving water as the only byproduct. The reaction sequence can be performed in one pot or as a three-step procedure. The synthetic applicability is demonstrated by the preparation of different α-amidoketones in moderate to good yields.

Full text of DOI:10.1021/acs.joc.5b02851

Note
pubs.acs.org/joc
Synthesis of α‑Amidoketones from Vinyl Esters via a Catalytic/
Thermal Cascade Reaction
Katharina Holthusen, Walter Leitner,* and Giancarlo Francio*
̀
Institut fur Technische und Makromolekulare Chemie, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany
̈
S
* Supporting Information
ABSTRACT: A straightforward, modular, and atom-efficient
method is reported for the synthesis of α-amidoketones from
vinyl esters via a cascade reaction including hydroformylation,
condensation with a primary amine, and a rearrangement step
giving water as the only byproduct. The reaction sequence can
be performed in one pot or as a three-step procedure. The
synthetic applicability is demonstrated by the preparation of
different α-amidoketones in moderate to good yields.
he α-amidoketone structural motif can often be found in
from the hydroformylation of easily accessible or even
commercially available vinyl esters.
T
biologically active compounds such as enzyme inhibitors,1
herbicides,2 or fungicides.3 Several approaches for their
synthesis have been reported in recent years. For instance, α-
amidoketones are accessible via a palladium-catalyzed oxidation
of allylic amides.4 In 2003 Bunce et al. described a multistep
synthesis starting from either nitrophenol or fluorinated
nitrobenzene.2 Cantet et al. reported the synthesis of α-
amidoketones from alkynylated amides obtained by direct
alkylation using NaH.5 Cyclic α-amidoketones can be generated
by DPU-promoted cyclization of alkynyl-substituted benza-
mides.6 Recently, Yamamoto and co-workers described the
synthesis of α-amidoketones starting from methyleneaziridines.
The palladium catalyzed ring-opening reaction of a methylene-
aziridine with a carboxylic acid gives a N,O-acetal which then
rearranges to an α-amidoketone.1 Here, the starting material
was prepared by a base-induced 1,2-dehydro-bromination of 2-
(bromomethyl)aziridines synthesized from the corresponding
aldehydes.8 Lantos and Zhang described the formation of α-
amidoketones via a multihetero Cope rearrangement in 1994.7
An organocatalytic approach for the synthesis of α-
amidoketones via intermolecular aldehyde-imine cross-cou-
plings was reported by Murry et al. in 2001.9 In 2005 Miller and
co-workers introduced an asymmetric version of this cross-
coupling reaction.10 Moreover, α-amidoketones can be
synthesized from amino acids through the Dakin−West
reaction.11,12
In a preliminary experiment, when vinyl benzoate 1a was
reacted in the presence of a rhodium catalyst with syngas (20
bar) and isopropylamine at 120 °C, substantial amounts of the
α-amidoketone N-iso-propyl-N-(2-oxopropyl)benzamide 4a
were observed in the reaction mixture (Scheme 1).
Thus, the hydrogenation of the imine intermediate 3a is
much slower in comparison to the observed rearrangement
leading to the formation of the α-amidoketone 4a. To verify
whether the rearrangement step is Rh-catalyzed, the reaction of
the preformed aldehyde 2a with isopropylamine was inves-
tigated separately. Thus, the aldehyde 2a and isopropylamine
were dissolved in ethanol and heated at 120 °C in a sealed vial
1
in a microwave (300 W) for 2 h (Scheme 2). The H NMR
spectrum of the crude reaction mixture showed nearly full
conversion toward the rearranged product 4a confirming that
the rearrangement is just thermally induced.14
To study the scope of this approach, different branched
aldehydes were prepared by Rh-catalyzed hydroformylation of
vinyl esters using vinyl acetate 1b, vinyl pivalate 1c, vinyl
benzoate 1a, vinyl butyrate 1g, vinyl laurate 1h, vinyl 4-
methoxybenzoate 1d, vinyl 4-fluorobenzoate 1e, and vinyl 2-
naphthoate 1f as starting materials.15 The latter three
compounds were prepared by Pd-catalyzed esterification of
the corresponding acids with vinyl acetate, which served both as
reactant and as solvent (Scheme 3).16
During our investigations on the hydroaminomethylation13
of vinyl esters with primary amines, we found that the reaction
did not lead to the expected hydroaminomethylation products
but instead the formation of α-amidoketones was observed.
Herein we report the synthetic scope of this new atom-efficient
method for the preparation of α-amidoketones starting from a
primary amine and propanal-2-yl esters, which are obtained
Various commercially available monodentate and bidentate
phosphorus ligands were screened in the Rh-catalyzed
hydroformylation using 1a as the model substrate (see
Received: December 17, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b02851
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 1. Cascade Reaction Leading to the Formation of the α-Amidoketone 4a
ethanol. The primary amines were added, and the vials were
placed in the microwave. The reactions were performed at 120
°C for 4 h (300 W). The results are summarized in Table 2.
Scheme 2. Microwave-Promoted Rearrangement Reaction
Table 2. Synthesis of α-Amidoketones from Aldehydes and
a
Amines under Microwave Conditions
Scheme 3. Synthesis of Noncommercially Available Vinyl
Esters by Esterification
b
entry
product
R1
R2
yield [%]
1
4b
4c
4g
4h
4a
4i
Me
Ph
Ph
Ph
Ph
iPr
Bn
Ph
56
10
33
20
34
43
51
38
52
46
50
21
52
2
tBu
3
n-C3H7
n-C11H23
Ph
4
5
Supporting Information for details). Here, the Rh/triphenyl-
phosphite catalyst system led to the best results in terms of
activity and regioselectivity at a preparative scale of 5.0 mmol
and was therefore used in the hydroformylation of the vinyl
esters 1a−h. The results are summarized in Table 1. Full
conversion was achieved for all substrates with regioselectivities
of 88−97% toward the branched aldehydes.
6
Ph
7
4j
Ph
8
4k
4l
Ph
4-MeO-Ph
4-F-Ph
4-CF3-Ph
Ph
9
Ph
10
11
12
13
4m
4d
4e
4f
Ph
(4)-MeO-Ph
(4)-F-Ph
(2)-Nph
Ph
Ph
a
a
Table 1. Hydroformylation of the Vinyl Ester 1a−h
Vinyl ester (5.0 mmol), amine (5.1 mmol), ethanol (6 mL), 120 °C,
b
300 W, 4 h. Isolated yield after purification via column
chromatography (basic alumina, pentane/ethyl acetate = 2:1−3:1).
Several α-amidoketones with different acyl groups and
bearing different substituents at the nitrogen were synthesized
and isolated with an ∼50% yield in most cases. While a 56%
yield was obtained from the acetate derivative 2b and using
aniline as the amine, a lower yield of 10% was obtained starting
from propanal-2-yl pivalate 2c, probably because of the steric
bulkiness of the tert-butyl group (Table 2, entries 1 and 2).
When longer alkyl chains were applied in the R1 position, the
isolated yield decreased with increasing chain length. When the
reaction was performed starting from the 1-oxopropan-2-yl
butyrate 2g the corresponding α-amidoketone was isolated in
33% yield (Table 2, entry 3). The α-amidoketone derived from
1-oxopropan-2-yl dodecanoate 2h was obtained in just 20%
yield (Table 2, entry 4). The influence of different amines was
investigated using propanal-2-yl benzoate 2a as the aldehyde
component. The highest yield of this series was obtained with
4-fluoroaniline (52%, Table 2, entry 9). It appears that the
reaction sequence works best with less basic amines as
significantly lower isolated yields were obtained when
isopropylamine or benzylamine was used (Table 2, entries 5
and 6). Similar results compared to the benzoate derivative 2a
were achieved using both 2-naphthoate 2f and the electron-rich
b
b
entry
product
R
conv [%]
branched:linear
1
2
3
4
5
6
7
8
2b
2c
2a
2d
2e
2f
Me
tBu
Ph
>99
>99
>99
>99
>99
>99
>99
>99
92:8
88:12
97:3
(4)-MeO-Ph
(4)-F-Ph
(2)-Nph
n-C3H7
90:10
92:8
92:8
2g
2h
89:11
88:12
n-C11H23
a
Vinyl ester (5.0 mmol), [Rh(CO)2acac] (10 μmol), triphenylphos-
phite (40 μmol), toluene (0.5 mL), CO/H2 (1:1, 40 bar), 16 h, 60 °C.
b
1
Determined by H NMR.
Next, the reaction sequence imine formation/rearrangement
was investigated. Control experiments showed that the
purification of the aldehydes by column chromatography is
not necessary, as identical results were obtained using the crude
aldehydes from the hydroformylation reaction as starting
material. Consequently, the crude reaction mixtures were
directly transferred into the microwave vials and diluted with
B
DOI: 10.1021/acs.joc.5b02851
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
4-OMe-substituted benzoate 2d. In contrast, a low yield was
obtained with the electron-poor 4-fluorobenzoate derivative 2e
(Table 2, entries 11−13).
As mentioned above describing the original experiment
leading to the serendipitous discovery of this reaction sequence,
it is also possible to perform the complete reaction cascade in a
more “user-friendly” one-pot procedure. The reaction control,
however, is more challenging as the presence of the amine can
hamper the hydroformylation step or side reactions may occur,
e.g. the hydrogenation of the aldehyde intermediate.
These individual steps can also be combined, and the whole
reaction cascade can be carried out in one pot using a bidentate
diphosphine/Rh catalyst for the hydroformylation step. Thus,
whereas hydroaminomethylation products are obtained when
aryl or alkyl substituted olefins are used as substrates (Scheme
4, upper reaction), vinyl esters afford α-amidoketones (Scheme
4, bottom reaction) under similar conditions in decent yields.
Scheme 4. Hydroaminomethylation (R = Alkyl, Ar) vs α-
Amidoketone Formation (R = Acyl)
The ligand set already applied for the hydroformylation (see
Supporting Information, Table S1) was tested for the combined
hydroformylation/rearrangement reaction using vinyl benzoate
1a and isopropylamine as starting materials (see Supporting
Information, Table S2). When monodentate ligands were used,
unreacted starting material was recovered indicating that the
presence of the amine completely inhibited the hydro-
formylation step. In contrast, bidentate phosphine ligands
showed good activity in the reaction of vinyl benzoate under
“hydroaminomethylation” conditions. Among dppf, dppb, and
dppe, the best results were obtained with the latter diphosphine
ligand resulting in 53% and 58% yield, respectively (Figure 1).
EXPERIMENTAL SECTION
■
General Considerations. All reactions and manipulations were
performed using standard Schlenk techniques or in a glovebox under
an argon atmosphere. Microwave experiments were performed in a
CEM Discover/Explorer12 Hybrid microwave equipped with an
external infrared sensor for temperature measurement. Chemical shifts
were referenced to residual solvent peaks (1H NMR, 13C NMR). For
1
1
NMR peak assignments H,13C-HSQC and H,13C-HMBC measure-
ments were used. HRMS analyses were performed with high-pressure-
liquid chromatography (HPLC), equipped with a mass spectrometer
(MS/MS). Samples were ionized with electrospray ionization (ESI)
and quantified with high resolution Orbitrap XL. Dichloromethane
and toluene were dried over alumina and molecular sieves with a
solvent purification system. Vinyl esters were degassed through
freeze−pump−thaw cycles. Vinyl 4-methoxybenzoate 1d, vinyl 4-
fluorobenzoate 1e, and vinyl 2-naphthoate 1f were synthesized
according to literature procedures.16
Figure 1. Combined hydroformylation/rearrangement reaction in a
one-pot procedure. See Experimental Section for detailed conditions.
It is important to note that a certain level of dilution is
necessary to ensure full conversion. Thus, the reactions were
performed in 75 mL stainless steel autoclaves at a 3.0 mmol
scale using toluene (7.5 mL) as solvent and 1 mol % of
rhodium. After 16 h at 120 °C and 40 bar CO/H2, the reaction
of vinyl benzoate with isopropylamine and syngas afforded 4a
in a good yield of 80% (determined by NMR spectroscopy of
the crude mixture). The remaining 20% was the imine
intermediate 3a. After purification via column chromatography,
4a was obtained in 53% isolated yield. A similar trend was
observed for the reaction of vinyl acetate and aniline resulting
in 76% 4b and 24% 3b at full conversion of the starting
material. The desired α-amidoketone 4b was isolated in 58%
yield after column chromatography. Thus, for both trans-
formations slightly higher yields were obtained using the one-
pot approach when compared to the three-step procedure.
A novel protocol for the synthesis of α-amidoketones from
primary amines and propanal-2-yl esters obtained by
regioselective hydroformylation of readily available vinyl esters
has been developed. The imine key intermediate, which is
formed by condensation of the primary amine with the
branched aldehyde, undergoes a thermally induced rearrange-
ment to finally give the desired α-amidoketone. The reaction is
highly atom-efficient as the only formed byproduct is water. To
demonstrate the synthetic applicability of this method, several
α-amidoketones were synthesized in moderate to good yields
under microwave conditions by simply mixing a primary amine
and a propanal-2-yl ester formed via regioselective Rh-catalyzed
hydroformylation of the corresponding vinyl ester.
General Experimental Methods. GP-1: General Procedure for
the Synthesis of Vinyl Esters. The synthesis of the vinyl esters
proceeded in accordance to literature.16 A Schlenk flask was charged
with potassium hydroxide (280.6 mg, 5.0 mmol, 1.25 equiv),
palladium(II) acetate (898.0 mg, 4.0 mmol), and carboxylic acid
(10.0 mmol, 2.5 equiv). The solids were dissolved in vinyl acetate (100
mL), and the resulting reaction mixture was stirred overnight at 40 °C.
The reaction mixture was cooled to room temperature, filtered over a
Celite pad, and eluted with DCM. The solvents were removed using
the rotary evaporator. The crude product was purified by column
chromatography (Silica, pentane/ethyl acetate = 4:1).
GP-2: General Procedure for the Catalytic Hydroformylation.
Triphenyl phosphite (12.4 mg, 40.0 μmol, 4.0 equiv) was weighed into
a Schlenk tube under air. The Schlenk tube was evacuated and refilled
with argon three times. A solution of [Rh(CO)2acac] in toluene (20.0
mM, 0.5 mL, 10.0 μmol) was added, and the mixture was stirred for 10
min at room temperature. The respective substrate (5.0 mmol, 500
equiv) was added, and the reaction mixture was transferred to a 10 mL
stainless steel autoclave equipped with a glass inlet and a stirring bar.
The autoclave was pressurized with syngas (40 bar) and stirred for 16
h in a heating cone at 60 °C. After carefully releasing the pressure, the
reaction mixture was analyzed by NMR and GC.
GP-3: General Procedure for the Microwave-Assisted Rearrange-
ment Reaction. After the hydroformylation reaction the crude
reaction mixture was transferred into a microwave vial and diluted
with EtOH (6 mL). The respective amine (5.1 mmol, 1.02 equiv) was
added dropwise at 0 °C. The microwave vial was placed into the
microwave, and the reaction was performed over 4 h at 120 °C with
300 W. The reaction mixture was transferred into a round-bottom
flask, and the solvents were removed using first the rotary evaporator
C
DOI: 10.1021/acs.joc.5b02851
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
and then the high vacuum pump. The crude product was purified by
column chromatography (basic Al2O3, pentane/ethyl acetate = 2:1−
3:1).
128.4 (2× CH, Ar), 129.1 (Cq, Ar), 129.6 (2× CH, Ar), 133.0 (CH,
Ar), 166.6 (Cq, CO), 198.7 (CHO).
1-Oxopropan-2-yl Acetate 2b. Analytical data agree with
literature.17 1H NMR (300 MHz, CDCl3): δ = 1.30 (d, JH,H = 7.2
3
GP-4: General Procedure for the Catalytic Hydroformylation and
Subsequent Rearrangement Reaction. 1,2-Bis(diphenylphosphino)-
ethane (35.9 mg, 90.0 μmol, 3.0 equiv) was weighed into a Schlenk
tube under air. The Schlenk tube was evacuated and refilled with argon
three times. The ligand was dissolved in DCM (0.5 mL). A solution of
[Rh(CO)2acac] (7.7 mg, 30.0 μmol) in toluene (7.5 mL) was added,
and the mixture was stirred for 10 min at room temperature. The
respective substrate (3.0 mmol, 100.0 equiv) and amine (3.3 mmol,
110.0 equiv) were added, and the reaction mixture was transferred to a
75 mL stainless steel autoclave equipped with a glass inlet and a
stirring bar. The autoclave was pressurized with CO (10 bar) first and
afterward with hydrogen (50 bar) to obtain a final pressure of 60 bar.
The reaction mixture was stirred in a heating cone for 16 h at 90 °C
and then for 24 h at 120 °C. After the pressure was carefully released,
the reaction mixture was analyzed by NMR. The solvents were
removed using first the rotary evaporator and then the high vacuum
pump. The crude product was purified by column chromatography
(basic Al2O3, pentane/ethyl acetate = 3:1).
3
Hz, 3H, CH3), 2.07 (s, 3H, CH3), 4.97 (q, JH,H = 7.2 Hz, 1H, CH),
9.39 (s, 1H, CHO) ppm. 13C{1H} NMR (75 MHz, CDCl3): δ = 13.6
(CH3), 21.1 (CH3), 74.4 (CH), 170.0 (Cq, CO), 197.9 (CHO) ppm.
1-Oxopropan-2-yl Pivalate 2c. Analytical data agree with
literature.17 1H NMR (300 MHz, CDCl3): δ = 1.18 (s, 9H, C(CH3)3),
3
3
1.33 (d, JH,H = 7.2 Hz, 3H, CH3), 4.96 (q, JH,H = 7.2 Hz, 1H, CH),
9.40 (s, 1H, CHO) ppm. 13C{1H} NMR (75 MHz, CDCl3): δ = 14.2
(CH3), 27.2 (3× CH3), 38.8 (Cq) 74.5 (CH), 178.1 (Cq, CO), 198.6
(CHO) ppm.
1-Oxopropan-2-yl 4-Methoxybenzoate 2d. Analytical data agree
with literature.17 1H NMR (400 MHz, CDCl3): δ = 1.51 (d, 3JH,H = 7.2
Hz, 3H, CH3), 3.86 (s, 3H, OCH3), 5.24 (q, 3JH,H = 7.2 Hz, 1H, CH),
7.93 (m, 2H, Ar−CH), 8.04 (m, 2H, Ar−CH), 9.65 (s, 1H, CHO)
ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 14.5 (CH3), 55.5
(OCH3), 74.9 (CH), 113.9 (2× CH, Ar), 121.5 (Cq, Ar), 132.0 (2×
CH, Ar), 163.9 (Cq, Ar), 165.8 (Cq, CO), 199.1 (CHO) ppm. IR
̃
(ATR): ν = 2938, 2841, 1707, 1646, 1604, 1581, 1511, 1458, 1422,
1316, 1292, 1250, 1167, 1097, 1069, 1025, 911, 846, 822, 785, 768,
Vinyl 4-Methoxybenzoate 1d. The compound was synthesized
following the general procedure for the synthesis of vinyl esters GP-1
starting from 4-methoxybenzoic acid. The product was obtained as a
colorless solid after column chromatography (Silica, pentane/ethyl
acetate = 4:1, Rf = 0.64). The obtained chemical shifts fit the reported
732, 696, 636, 610, 512, 414 cm−1. HR-MS (ESI): m/z = 209.0802,
+
calculated for C11H13O4 (M−H+): 209.0808.
1-Oxopropan-2-yl 4-Fluorobenzoate 2e. Analytical data agree with
literature.17 1H NMR (400 MHz, CDCl3): δ = 1.54 (d, 3JH,H = 7.2 Hz,
3
ones.16 Yield: m = 1.39 g (7.8 mmol, 78%). H NMR (300 MHz,
1
3H, CH3), 5.28 (q, JH,H = 7.2 Hz, 1H, CH), 7.12 (m, 2H, Ar−CH),
8.10 (m, 2H, Ar−CH), 9.64 (s, 1H, CHO) ppm. 13C{1H} NMR (100
MHz, CDCl3): δ = 14.3 (CH3), 75.2 (CH), 115.7 (d, 2JC,F = 22.1 Hz,
2× CH, Ar), 125.4 (d, 4JC,F = 3.0 Hz, Cq, Ar), 132.5 (d, 3JC,F = 9.5 Hz,
2× CH, Ar), 165.0 (Cq, CO), 166.1 (d, 1JC,F = 254.9 Hz, Cq, Ar), 198.3
(CHO) ppm. 19F NMR (377 MHz, CDCl3): δ = −104.5 ppm. IR
CDCl3): δ = 3.88 (s, 3H, OCH3), 4.67 (dd, 2JH,H = 1.5 Hz, 3JH,H = 6.3
2
3
Hz, 1H, CH2), 5.03 (dd, JH,H = 1.5 Hz, JH,H = 14.0 Hz, 1H, CH2),
3
3
6.94 (m, 2H, Ar−CH), 7.50 (dd, JH,H = 6.3 Hz, JH,H = 14.0 Hz, 1H,
CH), 8.06 (m, 2H, Ar−CH) ppm. 13C{1H} NMR (75 MHz, CDCl3):
δ = 55.5 (CH3), 97.7 (CH2), 113.9 (2× CH, Ar), 121.3 (Cq, Ar), 132.3
(2× CH, Ar), 141.6 (CH), 163.7 (Cq, Ar), 164.4 (Cq, CO) ppm.
Vinyl 4-Fluorobenzoate 1e. The compound was synthesized
following the general procedure for the synthesis of vinyl esters GP-
1 starting from 4-fluorobenzoic acid. The product was obtained as a
colorless solid after column chromatography (Silica, pentane/ethyl
acetate = 4:1, Rf = 0.73). The obtained chemical shifts fit the reported
̃
(ATR): ν = 2992, 1716, 1646, 1603, 1507, 1449, 1412, 1325, 1292,
1260, 1237, 1154, 1130, 1105, 1088, 1069, 1014, 948, 852, 824, 800,
764, 687, 624, 607, 503 cm−1. HR-MS (ESI): m/z = 197.0606,
calculated for C10H10O3F+ (M−H+): 197.0608.
1-Oxopropan-2-yl 2-Naphthoate 2f. Analytical data agree with
literature.17 1H NMR (400 MHz, CDCl3): δ = 1.45 (d, 3JH,H = 7.2 Hz,
3
3H, CH3), 5.24 (q, JH,H = 7.2 Hz, 1H, CH), 7.36−7.48 (m, 2H, Ar−
ones.16 Yield: m = 1.08 g (6.5 mmol, 65%). H NMR (300 MHz,
1
3
CH), 7.72 (m, 2H, Ar−CH), 7.80 (d, JH,H = 8.0 Hz, 1H, Ar−CH),
2
3
CDCl3): δ = 4.70 (dd, JH,H = 1.7 Hz, JH,H = 6.3 Hz, 1H, CH2), 5.06
(dd, 2JH,H = 1.7 Hz, 3JH,H = 14.0 Hz, 1H, CH2), 7.13 (m, 2H, Ar−CH),
7.48 (dd, 3JH,H = 6.3 Hz, 3JH,H = 14.0 Hz, 1H, CH), 8.12 (m, 2H, Ar−
CH) ppm. 13C{1H} NMR (75 MHz, CDCl3): δ = 98.4 (CH2), 115.8
(d, 2JC,F = 22.1 Hz, 2× CH, Ar), 125.2 (d, 4JC,F = 3.0 Hz, Cq, Ar), 132.6
(d, 3JC,F = 9.5 Hz, 2× CH, Ar), 141.3 (CH), 162.7 (Cq, CO), 166.2 (d,
1JC,F = 255.1 Hz, Cq, Ar) ppm. 19F NMR (282 MHz, CDCl3): δ =
−104.4 ppm.
7.96 (m, 1H, Ar−CH), 8.54 (s, 1H, Ar−CH), 9.59 (s, 1H, CHO)
ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 14.1 (CH3), 75.0 (CH),
124.9 (CH, Ar), 126.1 (Cq, Ar), 126.6 (CH, Ar), 127.5 (CH, Ar),
128.1 (CH, Ar), 128.3 (CH, Ar), 129.1 (CH, Ar), 131.3 (CH, Ar),
132.2 (Cq, Ar), 135.5 (Cq, Ar), 165.8 (Cq, CO), 198.4 (CHO) ppm.
̃
IR (ATR): ν = 3060, 2988, 2939, 2820, 1710, 1645, 1631, 1599, 1578,
1508, 1466, 1388, 1354, 1325, 1275, 1266, 1224, 1193, 1129, 1088,
1067, 955, 911, 865, 825, 776, 760, 731, 634, 596, 584, 516, 472 cm−1.
+
HR-MS (ESI): m/z = 229.0862, calculated for C14H13O3 (M−H+):
Vinyl 2-Naphthoate 1f. The compound was synthesized following
the general procedure for the synthesis of vinyl esters GP-1 starting
from 2-naphthoic acid. The product was obtained as a colorless liquid
after column chromatography (Silica, pentane/ethyl acetate = 4:1, Rf =
0.87). Analytical data agree with literature.17 Yield: m = 1.49 g (7.5
mmol, 75%). 1 H NMR (300 MHz, CDCl3): δ = 4.63 (dd, 2JH,H = 1.7
Hz, 3JH,H = 6.3 Hz, 1H, CH2), 5.02 (dd, 2JH,H = 1.7 Hz, 3JH,H = 14.0 Hz,
1H, CH2), 7.37−7.53 (m, 3H, 2× Ar−CH, CH), 7.74 (m, 2H, Ar−
CH), 7.82 (m, 1H, Ar−CH), 7.97 (m, 1H, Ar−CH), 8.54 (s, 1H, Ar−
CH) ppm. 13C{1H} NMR (75 MHz, CDCl3): δ = 98.3 (CH2), 125.2
(CH), 126.1 (Cq, Ar), 126.8 (CH, Ar), 127.8 (CH, Ar), 128.4 (CH,
Ar), 128.6 (CH, Ar), 129.5 (CH, Ar), 131.8 (CH, Ar), 132.4 (Cq, Ar),
229.0859.
1-Oxopropan-2-yl Butyrate 2g. Analytical data agree with
literature.18 1H NMR (400 MHz, CDCl3): δ = 0.97 (t, JH,H = 7.4
3
Hz, 3H, CH3), 1.38 (d, 3JH,H = 7.2 Hz, 3H, CH3), 1.69 (m, 2H, CH2),
2.39 (dt, 3JH,H = 7.5 Hz, 2JH,H = 2.2 Hz, 2H, CH2), 5.06 (q, 3JH,H = 7.2
Hz, 1H, CH), 9.51 (s, 1H, CHO) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ = 13.6 (CH3), 14.1 (CH3), 18.4 (CH2), 35.8 (CH2), 74.4
(CH), 173.1 (Cq, CO), 198.6 (CHO) ppm.
1-Oxopropan-2-yl Dodecanoate 2h. Analytical data agree with
literature.18 1H NMR (400 MHz, CDCl3): δ = 0.87 (t, 3JH,H = 6.7 Hz,
3H, CH3), 1.21−1.34 (m, 16H, 8× CH2), 1.38 (d, 3JH,H = 7.3 Hz, 3H,
CH3), 1.65 (m, 2H, CH2), 2.40 (dt, 3JH,H = 7.5 Hz, 2JH,H = 2.0 Hz, 2H,
̃
135.8 (Cq, Ar), 141.6 (CH), 163.8 (Cq) ppm. IR (ATR): ν = 3060,
3
1724, 1643, 1631, 1598, 1509, 1467, 1389, 1355, 1294, 1277, 1265,
1222, 1190, 1134, 1127, 1081, 946, 911, 864, 823, 773, 759, 696, 634,
CH2), 5.06 (q, JH,H = 7.2 Hz, 1H, CH), 9.52 (s, 1H, CHO) ppm.
13C{1H} NMR (100 MHz, CDCl3): δ = 14.1 (CH3), 14.2 (CH3), 22.7
(CH2), 24.9 (CH2), 29.1 (CH2), 29.2 (CH2), 29.3 (CH2), 29.4 (CH2),
29.6 (2× CH2), 31.9 (CH2), 34.0 (CH2), 74.4 (CH), 173.3 (Cq, CO),
198.6 (CHO) ppm.
597, 585, 528, 516, 471 cm−1. HR-MS (ESI): m/z = 199.0754,
+
calculated for C13H11O (M−H+): 199.0754.
2
1-Oxopropan-2-yl Benzoate 2a. Analytical data agree with
literature.17 1H NMR (300 MHz, CDCl3): δ = 1.45 (d, JH,H = 7.2
3
N-Isopropyl-N-(2-oxopropyl)benzamide 4a. The compound was
obtained as a colorless liquid after column chromatography (basic
Al2O3, pentane/ethyl acetate = 3:1, Rf = 0.23). Yield: m = 372.8 mg
3
Hz, 3H, CH3), 5.21 (q, JH,H = 7.2 Hz, 1H, CH), 7.40 (m, 2H, Ar−
CH), 7.52 (m, 1H, Ar), 8.00 (m, 2H, Ar−CH), 9.50 (s, 1H, CHO)
ppm. 13C{1H} NMR (75 MHz, CDCl3) δ = 14.4 (CH3), 75.0 (CH),
(1.7 mmol, 34%). H NMR(400 MHz, CDCl3): δ = 1.00 (d, JH,H
=
1
3
D
DOI: 10.1021/acs.joc.5b02851
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
3
6.7 Hz, 6H, 2×CH3), 2.16 (s, 3H, CH3), 3.95 (sept, JH,H = 6.7 Hz,
1H, CH), 4.00 (s, 2H, CH2), 7.32 (s, 5H, 5× Ar−CH) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ [ppm]: 20.8 (2× CH3), 27.3 (CH3), 49.9
(CH), 49.9 (CH2), 126.1 (2× CH, Ar), 128.5 (2× CH, Ar), 129.4
(CH, Ar), 136.3 (Cq, Ar), 171.4 (Cq, NCO), 202.8 (Cq, CO) ppm. IR
mp = 73.1 °C. Yield: m = 788.7 mg (2.6 mmol, 52%). 1H NMR (400
MHz, CDCl3): δ = 2.27 (s, 3H, CH3), 4.72 (s, 2 H, CH2), 7.22−7.06
(m, 5H, 5× Ar−CH), 7.46−7.34 (m, 3H, 3× Ar−CH), 7.59 (m, 1H,
Ar−CH), 7.75−7.68 (m, 2H, 2× Ar−CH), 7.94 (m, 1H, Ar−CH)
ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 27.4 (CH3), 60.5
(CH2), 125.5 (CH, Ar), 126.4 (CH, Ar), 126.9 (CH, Ar), 127.2 (CH,
Ar), 127.3 (CH, Ar), 127.4 (2× CH, Ar), 127.6 (CH, Ar), 128.7 (CH,
Ar), 129.2 (2× CH, Ar), 129.7 (CH, Ar), 132.4 (Cq, Ar), 132.5 (Cq,
Ar), 133.7 (Cq, Ar), 144.0 (Cq, Ar), 170.4 (Cq, NCO), 202.5 (Cq, CO)
̃
(ATR): ν = 2977, 2934, 1730, 1625, 1601, 1578, 1496, 1433, 1400,
1360, 1341, 1223, 1201, 1170, 1127, 1073, 1040, 1026, 986, 919, 882,
851, 783, 736, 700, 657, 630, 617, 609, 570, 544, 496, 479, 409 cm−1.
HR-MS (ESI): m/z = 220.1343, calculated for C13H18NO 2+ (M−H+):
220.1332.
̃
ppm. IR (ATR): ν = 3367, 3053, 2962, 2929, 1962, 1735, 1719, 1635,
N-(2-Oxopropyl)-N-phenylacetamide 4b. Analytical data agree
with literature.5 The compound was obtained as a dark orange oil after
column chromatography (basic Al2O3, pentane/ethyl acetate = 3:1, Rf
= 0.23). Yield: m = 535.4 mg (2.8 mmol, 56%). 1 H NMR (400 MHz,
CDCl3): δ = 1.84 (s, 3H, CH3), 2.08 (s, 3H, CH3), 4.36 (s, 2H, CH2),
7.21−7.36 (m, 5H, 5× Ar−CH) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ = 22.1 (CH3), 27.1 (CH3), 59.3 (CH2), 127.9 (2× CH,
Ar), 128.1 (CH, Ar), 129.7 (2× CH, Ar), 143.5 (Cq, Ar), 170.7 (Cq,
1626, 1593, 1574, 1497, 1468, 1458, 1410, 1380, 1351, 1325, 1313,
1285, 1245, 1228, 1196, 1169, 1149, 1124, 1094, 1083, 1067, 1036,
1016, 1002, 987, 971, 965, 957, 917, 902, 864, 823, 774, 761, 729, 699,
662, 640, 623, 585, 551, 515, 476, 440, 433, 412 cm−1. HR-MS (ESI):
+
m/z = 304.1326, calculated for C20H18NO2 (M−H+): 304.1332.
N-(2-Oxopropyl)-N-phenylbutyramide 4g. The compound was
obtained as a dark yellow oil after column chromatography (basic
Al2O3, pentane/ethyl acetate = 2:1, Rf = 0.42). Yield: m = 361.1 mg
1
3
NCO), 202.4 (Cq, CO) ppm. HR-MS (ESI): m/z = 192.1012,
(1.6 mmol, 33%). H NMR (400 MHz, CDCl3): δ = 0.74 (t, JH,H
=
+
calculated for C11H14NO (M−H+): 192.1019.
3
7.4 Hz, 3H, CH3), 1.50 (m, 2H, CH2), 2.02 (t, JH,H = 7.4 Hz, 2H,
CH2), 2.07 (s, 3H, CH3), 4.34 (s, 2 H, CH2), 7.20−7.27 (m, 3H, 3×
Ar−CH), 7.28−7.34 (m, 2H, 2× Ar−CH) ppm. 13C{1H} NMR (100
MHz, CDCl3): δ = 13.7 (CH3), 18.6 (CH2), 27.1 (CH3), 35.5 (CH2),
59.4 (CH2), 128.0 (3× Ar−CH), 129.6 (2× Ar−CH), 143.1 (Cq, Ar),
2
N-(2-Oxopropyl)-N-phenylpivalamide 4c. The compound was
obtained as a dark orange oil after column chromatography (basic
Al2O3, pentane/ethyl acetate = 3:1, Rf = 0.22). Yield: m = 116.7 mg
1
(0.5 mmol, 10%). H NMR (400 MHz, CDCl3): δ = 1.04 (s, 9H,
C(CH3)), 2.15 (s, 3H, CH3), 4.27 (s, 2H, CH2), 7.30−7.42 (m, 5H,
5× Ar−CH) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 27.2 (CH
3), 29.4 (3× CH3), 40.7 (Cq), 62.9 (CH2), 128.3 (CH, Ar), 129.2 (2×
CH, Ar), 129.7 (2× CH, Ar), 144.3 (Cq, Ar), 177.8 (Cq, NCO), 202.7
̃
173.1 (Cq, NCO), 202.5 (Cq,CO) ppm. IR (ATR): ν = 1733, 1652,
1595, 1495, 1411, 1383, 1350, 1293, 1212, 1169, 1067, 700, 552 cm−1.
HR-MS (ESI): m/z = 220.1326, calculated for C13H18NO2+ (M−H +):
220.1332.
N-(2-Oxopropyl)-N-phenyldodecanamide 4h. The compound was
obtained as a dark yellow oil after column chromatography (basic
Al2O3, pentane/ethyl acetate = 2:1, Rf = 0.45). Yield: m = 351.5 mg
̃
(Cq, CO) ppm. IR (ATR): ν = 3353, 2960, 2932, 2873, 1727, 1633,
1594, 1495, 1480, 1452, 1442, 1408, 1396, 1358, 1298, 1228, 1202,
1167, 1061, 1027, 1003, 973, 936, 771, 750, 703, 652, 617, 583, 565,
1
3
490, 432 cm−1. HR-MS (ESI): m/z = 234.1487, calculated for
(1.0 mmol, 20%). H NMR (400 MHz, CDCl3): δ = 0.87 (t, JH,H =
+
C14H20NO (M−H+): 234.1489.
6.8 Hz, 3H, CH3), 1.10−1.33 (m, 16H, 8× CH2), 1.55 (m, 2H, CH2),
2.11 (m, 2H, CH2), 2.16 (s, 3H, CH3), 4.41 (s, 2H, CH2), 7.24−7.44
(m, 5H, 5× Ar−CH) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ =
2
4-Methoxy-N-(2-oxopropyl)-N-phenylbenzamide 4d. The com-
pound was obtained as light yellow crystals after column
chromatography (basic Al2O3, pentane/ethyl acetate = 3:1, Rf1 =
0.19), mp = 125.0 °C. Yield: m = 708.3 mg (2.5 mmol, 50%). H
NMR (400 MHz, CDCl3): δ = 2.23 (s, 3H, CH3), 3.73 (s, 3H,
OCH3), 4.64 (s, 2H, CH2), 6.66 (m, 2H, 2× Ar−CH), 7.18−7.06 (m,
3H, 3× Ar−CH), 7.32−7.19 (m, 4H, 4× Ar−CH) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ = 27.3 (CH3), 55.2 (OCH3), 60.5 (CH2),
113.0 (2× CH, Ar), 126.7 (CH, Ar), 127.0 (Cq, Ar), 127.3 (2× CH,
Ar), 129.2 (2× CH, Ar), 131.1 (2× CH, Ar), 144.4 (Cq, Ar), 160.9
14.1 (CH ), 22.7 (CH2), 25.3 (CH2), 27.2 (CH3), 29.2 (CH2), 29.3
3
(2× CH2), 29.4 (CH2), 29.6 (2× CH2), 31.9 (CH2), 33.7 (CH2), 59.4
(CH2), 128.1 (Ar−CH), 128.1 (2× Ar−CH), 129.7 (2× Ar−CH),
143.2 (C , Ar), 173.5 (C , NCO), 202.6 (C , CO) ppm. IR (ATR): ν
̃
q
q
q
= 2922, 2853, 1735, 1657, 1596, 1495, 1412, 1382, 1357, 1169, 700,
+
552 cm−1. HR-MS (ESI): m/z = 332.2577, calculated for C21H34NO2
+
(M−H ): 332.2584.
N-Benzyl-N-(2-oxopropyl)benzamide 4i. Analytical data agree with
literature.1 The compound was obtained as yellow crystals after
column chromatography (basic Al2O3, pentane/ethyl acetate = 3:1, Rf
= 0.41), mp = 77.8 °C. Yield: m = 574.8 mg (2.2 mmol, 43%).
̃
(Cq, Ar), 170.0 (Cq, NCO), 202.7 (Cq, CO) ppm. IR (ATR): ν =
3073, 3018, 2963, 2934, 2840, 2052, 1979, 1900, 1724, 1632, 1606,
1593, 1578, 1514, 1495, 1462, 1453, 1445, 1410, 1370, 1325, 1310,
1283, 1251, 1228, 1185, 1173, 1155, 1117, 1071, 1039, 1025, 974, 958,
916, 846, 820, 807, 799, 772, 759, 709, 699, 693, 656, 630, 599, 564,
534, 491, 479, 447, 433 cm−1. HR-MS (ESI): m/z = 284.1279,
1
Rotation isomer major: H NMR (400 MHz, CDCl3): δ = 2.15 (s,
3H, CH3), 4.19 (s, 2H, CH2), 4.56 (s, 2H, CH2), 7.12−7.57 (m, 10H,
10x Ar−CH) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 27.5
(CH3), 53.9 (CH2), 54.2 (CH2,), 126.9 (2× CH, Ar), 127.0 (2× CH,
Ar), 127.9 (CH, Ar), 128.6 (2× CH, Ar), 129.0 (2× CH, Ar), 130.0
(CH, Ar), 135.3 (Cq, Ar), 136.2 (Cq, Ar), 172.5 (Cq, NCO), 202.6
(Cq, CO) ppm. Rotation isomer minor: 1H NMR (400 MHz,
CDCl3): δ = 1.88 (s, 3H, CH3), 3.90 (s, 2H, CH2), 4.76 (s, 2H, CH2),
7.12−7.57 (m, 10H, 10x Ar−CH) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ = 27.0 (CH3), 49.1 (CH2), 57.6 (CH2), 126.4 (2× CH,
Ar), 127.8 (CH, Ar), 128.5 (2× CH, Ar), 128.6 (2× CH, Ar), 128.8
(2× CH, Ar), 129.9 (CH, Ar), 136.0 (Cq, Ar), 136.5 (Cq, Ar), 172.4
(Cq, Ar), 203.1 (Cq, CO) ppm. HR-MS (ESI): m/z = 268.1347,
+
calculated for C17H18NO3 (M−H+): 284.1281.
4-Fluoro-N-(2-oxopropyl)-N-phenylbenzamide 4e. The com-
pound was obtained as a dark yellow oil after column chromatography
(basic Al2O3, pentane/ethyl acetate = 3:1, Rf = 0.23). Yield: m = 284.9
1
mg (1.1 mmol, 21%). H NMR (400 MHz, CDCl3): δ = 2.09 (s, 3H,
CH3), 4.51 (s, 2 H, CH2), 6.70 (m, 2H, 2× Ar−CH), 6.94 (m, 2H, 2×
Ar−CH), 7.01(m, 1H, Ar−CH), 7.08 (m, 2H, 2× Ar−CH), 7.20 (m,
2H, 2× Ar−CH) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 27.3
2
(CH3), 60.4 (CH2), 114.9 (d, JC,F = 22 Hz, 2× CH, Ar), 127.0 (CH,
Ar), 127.3 (2× CH, Ar), 129.3 (2× CH, Ar), 131.1 (d, 4JC,F = 3.3 Hz,
Cq, Ar), 131.2 (d, 3JC,F = 8.7 Hz, 2× CH, Ar), 143.9 (Cq, Ar), 163.4 (d,
+
calculated for C17H18NO2 (M−H+): 268.1332.
1JC,F = 250.3 Hz, Cq, Ar), 169.4 (Cq, NCO), 202.2 (Cq, CO) ppm. 19
F
N-(2-Oxopropyl)-N-phenylbenzamide 4j. The compound was
obtained as yellow crystals after column chromatography (basic
Al2O3, pentane/ethyl acetate = 3:1, Rf = 0.40), mp = 88.1 °C. Yield: m
= 645.9 mg (2.6 mmol, 51%). 1H NMR (400 MHz, CDCl3): δ = 2.12
(s, 3H, CH3), 4.56 (s, 2H, CH2), 6.99−7.13 (m, 8H, 8× Ar−CH),
7.23−7.25 (m, 2H, 2× Ar−CH) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ = 27.3 (CH3), 60.3 (CH2), 126.9 (CH, Ar), 127.4 (2× CH,
Ar), 127.7 (2× CH, Ar), 128.8 (2× CH, Ar), 129.2 (2× CH, Ar),
129.9 (CH, Ar), 135.1 (Cq, Ar), 143.9 (Cq, Ar), 170.5 (Cq, NCO),
̃
NMR (377 MHz, CDCl3): δ = −109.57 ppm. IR (ATR): ν = 3378,
3055, 2928, 1725, 1636, 1600, 1506, 1493, 1455, 1441, 1411, 1372,
1320, 1307, 1268, 1224, 1178, 1153, 1113, 1100, 1090, 1070, 1035,
1013, 992, 964, 915, 851, 815, 767, 749, 698, 690, 630, 607, 596, 558,
519, 483, 443, 407 cm−1. HR-MS (ESI): m/z = 272.1078, calculated
for C16H15NO F+ (M−H+): 272.1081.
2
N-(2-Oxopropyl)-N-phenyl-2-naphthamide 4f. The compound
was obtained as a yellow oil, which slowly crystallizes after column
chromatography (basic Al2O3, pentane/ethyl acetate = 3:1, R f = 0.41),
202.4 (Cq, CO) ppm. IR (ATR): ν
̃
= 3057, 3026, 2969, 2927, 1724,
E
DOI: 10.1021/acs.joc.5b02851
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1646, 1595, 1493, 1455, 1445, 1410, 1381, 1342, 1322, 1311, 1277,
1223, 1166, 1115, 1068, 1040, 1025, 1002, 977, 914, 785, 770, 727,
715, 694, 662, 628, 563, 521, 452 cm−1. HR-MS (ESI): m/z =
measurements and Dr. C. Schmitz for fruitful discussion.
Financial support by the European Regional Development
Fund (ERDF) and the state of North Rhine-Westphalia,
Germany, project “Sustainable Chemical Synthesis (Sus-
ChemSys)” is gratefully acknowledged.
+
254.1180, calculated for C16H16NO2 (M−H+): 254.1176.
N-(4-Methoxyphenyl)-N-(2-oxopropyl)benzamide 4k. The com-
pound was obtained as a dark yellow oil after column chromatography
(basic Al2O3, pentane/ethyl acetate = 2:1, Rf = 0.32). Yield: m = 532.3
mg (1.9 mmol, 38%). 1 H NMR (400 MHz, CDCl3): δ = 2.21 (s, 3H,
CH3), 3.71 (s, 3H, OCH3), 4.61 (s, 2H, CH2), 6.66−6.72 (m, 2H, 2×
Ar−CH), 6.99−7.06 (m, 2H, 2× Ar−CH), 7.12−7.19 (m, 2H, 2× Ar−
CH), 7.20−7.25 (m, 1H, Ar−CH), 7.29−7.35 (m, 2H, 2× Ar−CH)
ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 27.3 (CH3), 55.4
(OCH3), 60.5 (CH2), 114.3 (2× CH, Ar), 127.7 (2× CH, Ar), 128.7
(2× CH, Ar), 128.8 (2× CH, Ar), 129.7 (CH, Ar), 135.2 (Cq, Ar),
136.8 (Cq, Ar), 158.2 (Cq, Ar), 170.6 (Cq, NCO), 202.5 (Cq, CO)
REFERENCES
■
(1) Oh, B. H.; Nakamura, I.; Yamamoto, Y. J. Org. Chem. 2004, 69,
2856−2858.
(2) Bunce, R. A.; Herron, D. M.; Hale, L. Y. J. Heterocycl. Chem. 2003,
40, 1031−1039.
(3) Kohn, A.; Lehr, S.; Braun, R.; Dorner-Rieping, S.; Ahrens, H.;
̈
̈
Dietrich, H.; Hauser-Hahn, I.; Rosinger, C. H.; Gatzweiler, E. WO
̈
2013/087577 A1, 2013.
ppm. IR (ATR): ν
̃
= 1730, 1638, 1508, 1446, 1425, 1407, 1374, 1322,
(4) Hosokawa, T.; Aoki, S.; Takano, M.; Nakahira, T.; Yoshida, Y.;
Murahashi, S.-I. J. Chem. Soc., Chem. Commun. 1991, 1559−1560.
(5) Cantet, A.-C.; Carreyre, H.; Gesson, J.-P.; Jouannetaud, M.-P.;
Renoux, B. J. Org. Chem. 2008, 73, 2875−2878.
1291, 1246, 1225, 1173, 1026, 838, 721, 701, 611, 565 cm−1. HR-MS
+
(ESI): m/z = 284.1288, calculated for C17H18NO3 (M−H +):
284.1281.
N-(4-Fluorophenyl)-N-(2-oxopropyl)benzamide 4l. The com-
pound was obtained as a dark yellow oil after column chromatography
(basic Al2O3, pentane/ethyl acetate = 2:1, Rf = 0.37). Yield: m = 701.4
mg (2.6 mmol, 52%). 1 H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3H,
CH3), 4.63 (s, 2H, CH2), 6.85−6.92 (m, 2H, 2× Ar−CH), 7.05−7.13
(m, 2H, 2× Ar−CH), 7.14−7.21 (m, 2H, 2× Ar−CH), 7.25 (m, 1H,
Ar−CH), 7.28−7.34 (m, 2H, 2× Ar−CH) ppm. 13C{1H} NMR (100
MHz, CDCl3): δ = 27.3 (CH3), 60.2 (CH2), 116.0 (d, 2 JCF = 22.4 Hz,
(6) Chen, W.; Cui, J.; Zhu, Y.; Hu, X.; Mo, W. J. Org. Chem. 2012, 77,
1585−1591.
(7) Lantos, I.; Zhang, W.-Y. Tetrahedron Lett. 1994, 35, 5977−5980.
(8) De Kimpe, N.; De Smaele, D.; Sakonyi, Z. J. Org. Chem. 1997, 62,
2448.
(9) Murry, J. A.; Frantz, D. E.; Soheili, A.; Tillyer, R.; Grabowski, E. J.
J.; Reider, P. J. J. Am. Chem. Soc. 2001, 123, 9696−9697.
(10) Mennen, S. M.; Gipson, J. D.; Kim, Y. R.; Miller, S. J. J. Am.
Chem. Soc. 2005, 127, 1654−1655.
(11) Dakin, H. D.; West, R. J. Biol. Chem. 1928, 78, 745−756 and
757−764.
(12) For reviews, see: (a) Buchanan, G. L. Chem. Soc. Rev. 1988, 17,
91−109. (b) Behbahani, F. K. J. Chem. Res. 2013, 37, 513−522.
(13) For reviews, see: (a) Crozet, D.; Urrutigoity, M.; Kalck, P.
ChemCatChem 2011, 3, 1102−1118. (b) Raoufmoghaddam, S. Org.
Biomol. Chem. 2014, 12, 7179−7193.
3
2× Ar−CH), 127.9 (2× Ar−CH), 128.7 (2× Ar−CH), 129.3 (d, JCF
4
= 8.8 Hz, 2× Ar−CH), 130.0 (Ar−CH), 134.9 (Cq), 140.0 (d, JCF
=
1
3.1 Hz, Cq), 161.0 (d, JCF = 247.8 Hz, Cq), 170.6 (Cq, NCO), 202.2
(Cq,CO) ppm. 19F NMR (377 MHz, CDCl3): δ = −114.27 ppm. IR
̃
(ATR): ν = 1729, 1638, 1509, 1446, 1424, 1407, 1373, 1321, 1291,
1246, 1224, 1172, 1162, 1039, 1025, 838, 782, 720, 700, 611, 564
+
cm−1. HR-MS (ESI): m/z = 272.1080, calculated for C16H15FNO2
+
(M−H ): 272.1081.
N-(2-Oxopropyl)-N-(4-(trifluoromethyl)phenyl)benzamide 4m.
The compound was obtained as a dark yellow oil after column
chromatography (basic Al2O3, pentane/ethyl acetate = 2:1, Rf = 0.34).
Yield: m = 744.1 mg (2.3 mmol, 46%). 1H NMR (400 MHz, CDCl3):
δ = 2.25 (s, 3H, CH3), 4.69 (s, 2 H, CH2), 7.16−7.23 (m, 4H, 4× Ar−
CH), 7.27−7.7.35 (m, 3H, 3× Ar−CH), 7.43−7.49 (m, 2H, 2× Ar−
CH) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 27.3 (CH3), 60.0
(14) The imine intermediate 3a and the product 4a were obtained in
approximately equal amounts at 100 °C, whereas at 140 °C higher
amounts of 4a were formed albeit with several unidentified side
products deriving from the degradation of the imine intermediate. The
addition of water scavengers (4Å molecular sieve, MgSO4) does not
have a significant influence while acidic or basic additives (HBF4,
NEt3) led to reduced conversion. Consequently, all following
experiments were performed at 120 °C and without additives.
(15) Khan, S. R.; Bhanage, B. M. Catal. Commun. 2014, 46, 109−112.
(16) Martinez-Montero, S.; Fernandez, S.; Sanghvi, Y. S.; Gotor, V.;
Ferrero, M. Org. Biomol. Chem. 2011, 9, 5960−5966.
1
3
(CH2), 121.6 (q, JCF = 272.2 Hz, CF3), 126.3 (q, JCF = 3.6 Hz, 2×
2
Ar−CH), 127.4 (2× Ar−CH), 128.1 (2× Ar−CH), 128.2 (q, JC,F
=
51.5 Hz, Cq, Ar), 128.8 (2× Ar−CH), 130.5 (Ar−CH), 134.4 (Cq, Ar),
147.1 (Cq, Ar), 170.5 (Cq, NCO), 202.0 (Cq,CO) ppm. 19F NMR
̃
(377 MHz, CDCl3): δ = −62.52 ppm. IR (ATR): ν = 1652, 1612,
̀
(17) Schmitz, C.; Holthusen, K.; Leitner, W.; Francio, G. ACS Catal.
1320, 1161, 1107, 1065, 101, 834, 709 cm−1. HR-MS (ESI): m/z =
2016, 6, 1584−1589.
322.1058, calculated for C17H15F3NO2 (M−H+): 322.1049.
+
(18) Zhang, X.; Cao, B.; Yan, Y.; Yu, S.; Ji, B.; Zhang, X. Chem. - Eur.
J. 2010, 16, 871−877.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02851.
■
S
NMR spectra, IR spectra, and additional Tables S1 and
S2 (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: leitner@itmc.rwth-aachen.de.
*E-mail: francio@itmc.rwth-aachen.de.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank A. K. Beine for experimental support, H. Eschmann
for GC, W. Falter for GC/MS and B. Schieweck for HRMS
■
F
DOI: 10.1021/acs.joc.5b02851
J. Org. Chem. XXXX, XXX, XXX−XXX