Direct coupling of arylacetonitriles and primary alcohols to α-alkylated arylacetamides with complete atom economy catalyzed by a rhodium complex-triphenylphosphine- potassium hydroxide system

Article abstract of DOI:10.1002/adsc.201401013

A direct synthesis of α-alkylated arylacetamides from arylacetonitriles and primary alcohols has been accomplished for the first time. In the presence of the rhodium complex [Rh(cod)Cl]₂/triphenylphosphine/potassium hydroxide system, the desired α-alkylated arylacetamides were obtained in 74-92% yield under microwave conditions. The experimental results in this paper are in sharp contrast with previous reports, where the coupling of arylacetonitriles and primary alcohols produced the α-alkylated arylacetonitriles. Mechanistic investigations show that arylacetonitriles are first α-alkylated with primary alcohols to produce α-alkylated arylacetonitriles, which are further hydrated with the water resulting from the α-alkylation step to produce α-alkylated arylacetamides. More importantly, this research shows the potential of developing completely atom-economical reactions that involve the hydrogen autotransfer (or hydrogen borrowing) process.

Full text of DOI:10.1002/adsc.201401013

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DOI: 10.1002/adsc.201401013
Very Important Publication
Direct Coupling of Arylacetonitriles and Primary Alcohols to
a-Alkylated Arylacetamides with Complete Atom Economy
Catalyzed by a Rhodium Complex–Triphenylphosphine–
Potassium Hydroxide System
Feng Li,a,* Xiaoyuan Zou,a and Nana Wanga
a
Key Laboratory for Soft Chemistry and Functional Materials, Ministry of Education, Nanjing University of Science and
Technology, Nanjing 210 094, Peopleꢀs Republic of China
Fax : (+86)-25-8443-1939; e-mail: fengli@njust.edu.cn
Received: October 24, 2014; Revised: January 11, 2015; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201401013.
Abstract: A direct synthesis of a-alkylated arylacet- aryl
ACHTUNGTRENaNGNU cetonitriles are first a-alkylated with primary al-
ACHTUNGTRENNUNG
has been accomplished for the first time. In the pres- which are further hydrated with the water resulting
ence of the rhodium complex [Rh(cod)Cl]2/triphenyl- from the a-alkylation step to produce a-alkylated
phosphine/potassium hydroxide system, the desired arylacetACTHNUTRGNEUaGN mides. More importantly, this research
a-alkylated arylacetamides were obtained in 74–92% shows the potential of developing completely atom-
yield under microwave conditions. The experimental economical reactions that involve the hydrogen auto-
results in this paper are in sharp contrast with previ- transfer (or hydrogen borrowing) process.
ous reports, where the coupling of arylacetonitriles
and primary alcohols produced the a-alkylated aryl- Keywords: alcohols; complete atom economy; homo-
ACHTUNGTRENNUNGacetonitriles. Mechanistic investigations show that geneous catalysis; nitriles; rhodium
Introduction
We have reported a series of iridium-catalyzed
transformations with the activation of alcohols as
Maximizing the atom efficiency and minimizing the electrophiles.[4] As part of our continuing interest in
waste generation of a reaction are the most significant this field, we explored the potential of rhodium com-
and challenging goals of modern organic synthesis.[1] plexes as catalysts. Herein, we wish to demonstrate
In recent years, much attention has been focused on
À
the construction of C C bonds, which are the essen-
tial link in all organic molecules, via reactions of eno-
lates with the activation of alcohols as electrophiles
based on the hydrogen autotransfer (or hydrogen bor-
rowing) process using ruthenium, iridium or other
transition metal catalysts.[2,3] In this process, alcohols
are first dehydrogenated to form aldehydes with the
generation of metal hydride species, followed by con-
densation between enolates. The resulting aldehydes
produce unsaturated intermediates, which are further
hydrogenated by the metal hydride species that is
formed in the dehydrogenation step of alcohols, to
produce a-alkylated products (Scheme 1). Despite sig-
nificant advances, such transformations are not com-
pletely atom-economical reactions because water is
generated as a by-product in this process.
À
Scheme 1. Transition metal-catalyzed C C bond-forming re-
actions based on the hydrogen autotransfer (or hydrogen
borrowing) process.
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Scheme 2. Transition metal-catalyzed coupling of arylacetonitriles and alcohols.
the first example of the direct coupling of arylacetoni- Results and Discussion
triles and primary alcohols to afford a-alkylated aryl-
acetamides with complete atom economy (Scheme 2, Our initial experiment focused on the rhodium-cata-
right). The experimental results of this paper are in lyzed coupling of phenylacetonitrile (1a) and benzyl
sharp contrast with previous reports.[5] Several groups alcohol (2a). In the presence of [Rh(cod)Cl]2 (cod=
have reported the coupling of arylacetonitriles and 1,5-cyclooctadienyl) (1 mol%), DPPM [bis(diphenyl-
primary alcohols to afford the a-alkylated arylaceto- phosphino)methane]
(0.1 equiv.)
and
KOH
nitriles catalyzed by ruthenium,[5a,b] palladium,[5b] iri- (0.4 equiv.), the reaction of 1a and 2a was performed
dium[5c] and osmium complexes[5d] (Scheme 2, left). at 1308C in tert-amyl alcohol (anhydrous, ꢀ99%) for
The a-alkylated arylacetamides are ubiquitous struc- 17 h. This reaction generated the a-alkylated product
tural motifs in many natural products and pharma- 3aa in 76% yield and 2,3-diphenylpropanamide 4aa in
ceutically active compounds,[6] and they are used as 24% yield (Table 1, entry 1). Using PCy3 (tricyclohex-
the key synthetic intermediates to construct biologi- ylphosphine) as an alternative ligand, a similar result
cally active compounds.[7] Traditional methods to syn- was also observed (Table 1, entry 2). To our surprise,
thesize a-alkylated arylacetamides suffer from being the product 4aa could be obtained in 95% yield when
multistep reactions from arylacetic acids or their PPh3 was used as the ligand (Table 1, entry 3). Using
esters as the starting materials, using of a large K2CO3 or K3PO4, instead of KOH, the reactions pro-
amount of hazardous reagents and generating a large duced only 3aa (Table 1, entries 4 and 5). When
amount of harmful by-products.[6,7]
[Cp*RhCl2]2 or Rh(acac)(CO)2] was used as the cata-
lyst, the product 4aa was formed in only moderate
yields (Table 1, entries 6 and 7). The reaction of 1a
and 2a proceeded in the presence of the
Table 1. Reactions of phenylacetonitrile 1a with benzyl alcohol 2a under various
conditions.[a]
[a]
Reaction conditions: 1a (1 mmol), 2a (1.1 mmol), catalyst (1 mol%), ligand
(0.1 equiv.), base (x equiv.), tert-amyl alcohol (1 mL), 1308C, 17 h.
Yield was determined based on the H NMR spectrum of the crude reaction
mixture with 1,3,5-trimethoxybenzene as the internal standard.
MW.
[b]
[c]
1
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Direct Coupling of Arylacetonitriles and Primary Alcohols
Table 2. Reactions of phenylacetonitrile (1a) with various al-
cohols (2).[a]
Table 2. (Continued)
[a]
Reactions conditions: 1a (1 mmol),
2
(1.1 mmol),
[Rh(cod)Cl]2 (1 mol%), PPh3 (0.1 equiv.), KOH
(0.4 equiv.), tert-amyl alcohol (1 mL), MW, 1308C, 2 h.
Isolated yield.
[b]
[c]
2 (2 mmol).
[Rh(cod)Cl]2/PPh3/KOH system in a focused, single-
mode microwave synthesizer (Discover CEM, USA,
300 W) for 2 h to produce 4aa in 96% yield (Table 1,
entry 8). Apparently, microwave irradiation could ac-
celerate the reaction process. Any attempt to decrease
the amount of base and reduce the reaction tempera-
ture resulted in relatively low yields of product 4aa
(Table 1, entries 9 and 10).
With the established optimal reaction conditions
(Table 1, entry 8), the coupling of 1a and various alco-
hols (2) was examined, and these results are summar-
ized in Table 2. In analogy to the case of benzyl alco-
hol (2a) (Table 2, entry 1), the reactions with benzylic
alcohols that have an electron-donating group, such
as methyl (2b, 2c), isopropyl (2d) and methoxy (2e)
groups, generated the desired products (4ab–4ae) in
80–85% yields (Table 2, entries 2–5). The coupling
with benzylic alcohols that have a halogen atom, such
as fluoro (2f) and chloro (2g, 2h) generated the corre-
sponding products 4af–4ah in 81–88% yields (Table 2,
entries 6–8). The benzylic alcohol with a strong elec-
tron-deficient trifluoromethoxy group (2i) was also
proven to be a suitable substrate, and the desired
product (4ai) was obtained in 91% yield (Table 2,
entry 9). Furthermore, a high catalytic activity was ob-
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Table 3. Reactions of a series of arylacetonitriles (1) with
benzyl alcohol (2a).[a]
Table 3. (Continued)
[a]
Reactions conditions:
1
(1 mmol), 2a (1.1 mmol),
[Rh(cod)Cl]2 (1 mol%), PPh3 (0.1 equiv.), KOH
(0.4 equiv.), tert-amyl alcohol (1 mL), MW, 1308C, 2 h.
Isolated yield.
[b]
served in the transformations of naphthalenemethanol
(2j) and ferrocenemethanol (2k) (Table 2, entries 10
and 11). This coupling reaction was also applied to
aliphatic alcohols such as 1-butanol (2l) and 1-hexanol
(2m), which generated the desired products 4al and
4am in 74% and 76% yield, respectively, although the
addition of 2 equiv. of alcohols was required (Table 2,
entries 12 and 13). However, no reaction occurred
when secondary alcohols with high steric hindrance,
such as cyclohexanol and cyclopentanol, were used as
the substrates.
As shown in Table 3, the coupling of a series of
arylACTHNUTRGENUaGN cetonitriles (1) and benzyl alcohol (2a) was in-
vestigated. The transformations of phenylacetonitriles
with one or two electron-donating groups, such as
methyl (1b, 1c), methoxy (1d) and dimethoxy (1e),
led to the corresponding products (4ba–4ea) in 80–
91% yields (Table 3, entries 1–4). The reactions of
phenylacetonitriles with a halide atom such as fluoro
(1f, 1g) and chloro (1h) groups generated the desired
products (4fa–4ha) in 83–92% yields (Table 3, en-
tries 5–7). Furthermore, phenylacetonitriles with
a strong electron-withdrawing group such as trifluoro-
methyl (1i) and trifluoromethoxy (1j) moieties were
successfully converted to the corresponding products
(4ia and 4ja) in 84% and 90% yields, respectively
(Table 3, entries 8 and 9). In the case of 1-naphthalen-
ylacetonitrile (1k) and 2-naphthalenylacetonitrile (1l),
the desired products 4ka and 4la were isolated in
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Direct Coupling of Arylacetonitriles and Primary Alcohols
Scheme 3. Transformations of arylacetonitriles with a diol.
Scheme 4. Mechanistic experiments.
82% and 88% yields, respectively (Table 3, entries 10
and 11).
To obtain information on the reaction mechanism,
a series of experiments was performed. In the pres-
The transformations of arylacetonitriles with a diol ence of KOH, the condensation between phenylaceto-
were also investigated (Scheme 3). The reactions of nitrile (1a) and benzaldehyde (5) occurred at 1308C
phenylacetonitrile derivatives 1a, 1b and 1f with 1,3- for 2 h to generate the unsaturated product 6 in 89%
benzenedimethanol (2n) generated the desired prod- yield [Scheme 4, Eq, (1)]. Then, the catalytic hydroge-
ucts in 80–86% yield.
nation of the resulting 6 with benzyl alcohol (2a) as
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Scheme 5. Proposed mechanism of the reaction.
the hydrogen source was investigated. In the presence occurs to produce a,b-unsaturated nitriles and water.
of [Rh(cod)Cl]2 (1 mol%), PPh3 (0.1 equiv.) and KOH Furthermore, the addition of rhodium hydride into
(0.4 equiv.), the reaction of 6 with 2a was performed the C=C double bond of a,b-unsaturated nitriles pro-
for 2 h to obtain the product 3aa in 91% yield duces species C. The a-alkylated arylacetonitriles D
[Scheme 4, Eq. (2)]. Finally, the hydration of 6 and are released, and the catalytically active alkoxo rhodi-
3aa was examined. When the Rh(cod)Cl]2/PPh3/KOH um species A are regenerated via the reaction of spe-
system was used, the reaction of 6 with an equimolar cies C with alcohols. Finally, the hydration of a-alky-
amount of water was performed for 2 h, and no prod- lated arylacetonitriles D with the water, that results
uct was detected [Scheme 4, Eq. (3)]. It was found from the Knoevenagel condensation step, produces a-
that 3aa could be converted to the product 4aa in alkylated arylacetamides E.[8]
90% yield under identical reaction conditions
[Scheme 4, Eq. (4)]. It is speculated that a,b-unsatu-
rated nitriles are more stable than saturated nitriles Conclusions
under these reaction conditions due to the conjuga-
tive effect.
In summary, we have demonstrated the first example
A possible mechanism was proposed to account for of the direct synthesis of a-alkylated arylacetamides
this direct coupling of arylacetonitriles and primary from arylacetonitriles and alcohols. In the presence of
alcohols to afford a-alkylated arylacetamides a rhodium complex [Rh(cod)Cl]2/triphenylphosphine/
(Scheme 5). The initial step of the reaction involves potassium hydroxide system, a-alkylated arylacet-
the formation of alkoxo rhodium species A through
ACHTUNGTRENaNUNG mides could be obtained in 74–92% yield under mi-
the reaction of [Rh(cod)Cl]2 and alcohols under the crowave conditions. The mechanistic investigations
acceleration of the base. By means of the b-hydrogen show that arylacetonitriles are first a-alkylated with
elimination of the alkoxo rhodium species A, the rho- alcohols to produce a-alkylated arylacetonitriles,
dium hydride species B and aldehydes are generated. which are further hydrated with the resulting water
The base-catalyzed Knoevenagel condensation be- through an a-alkylation step to produce a-alkylated
tween arylacetonitriles and the resulting aldehydes arylacetamides. More importantly, this study demon-
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Direct Coupling of Arylacetonitriles and Primary Alcohols
CDCl3): d=175.4, 139.4, 139.3, 128.9, 128.6, 128.2, 127.9,
127.3, 126.1, 54.5, 39.2.
strates the potential of developing completely atom-
economical reactions that involve the hydrogen auto-
transfer (or hydrogen borrowing) process.
2-Phenyl-3-para-tolylpropanamide (4ab):[10] yellow solid;
yield: 202 mg (85%); mp 150–1518C; 1H NMR (500 MHz,
CDCl3): d=7.33–7.24 (m, 5H, ArH), 7.03–6.99 (m, 4H,
ArH), 5.33 (br s, 1H, NH), 5.29 (br s, 1H, NH), 3.62 (t, J=
7.6 Hz, 1H, CH), 3.49 (dd, J=13.6 Hz and 7.5 Hz, 1H, CH),
2.96 (dd, J=13.6 Hz and 7.2 Hz, 1H, CH), 2.28 (s, 3H,
CH3); 13C NMR (125 MHz, CDCl3): d=175.4, 139.4, 136.3,
135.6, 128.9, 128.8, 128.7, 128.0, 127.3, 54.8, 38.9, 21.0.
2-Phenyl-3-ortho-tolylpropanamide (4ac): brown solid;
yield: 195 mg (82%); mp 150–1518C; 1H NMR (500 MHz,
CDCl3): d=7.32–7.26 (m, 5H, ArH), 7.11–7.00 (m, 4H,
ArH), 5.37 (br s, 1H, NH), 5.29 (br s, 1H, NH), 3.62 (t, J=
7.2 Hz, 1H, CH), 3.54 (dd, J=13.9 Hz and 7.5 Hz, 1H, CH),
2.99 (dd, J=13.9 Hz and 7.2 Hz, 1H, CH), 2.25 (s, 3H,
CH3); 13C NMR (125 MHz, CDCl3): d=175.2, 139.6, 137.6,
136.2, 130.2, 129.6, 128.7, 128.0, 127.4, 126.3, 125.8, 53.4,
36.5, 19.4; HR-MS-EI (70 eV): m/z=262.1204, calcd. for
C16H17NONa [M+Na]+: 262.1208.
Experimental Section
General Experimental Details
High-resolution mass spectra (HR-MS) were obtained on
a HPLC-Q-Tof MS(Micro) spectrometer and are reported
as m/z (relative intensity). Accurate masses are reported for
the molecular ion [M+Na].+ Melting points were measured
on a X-6 micro-melting apparatus (Beijing Tech Instrument
Co., Ltd). Proton nuclear magnetic resonance (1H NMR)
spectra were recorded at 500 MHz using a Bruker Avance
500 spectrometer. Chemical shifts are reported in delta (d)
units, parts per million (ppm) downfield from trimethylsi-
lane or ppm relative to the center of the singlet at 7.26 ppm
for CDCl3 and 2.50 ppm for DMSO-d6. Coupling constants J
values are reported in Hertz (Hz), and the splitting patterns
were designated as follows: s, singlet; d, doublet; t, triplet;
m, multiplet; b, broad. Carbon-13 nuclear magnetic reso-
nance (13C NMR) spectra were recorded at 125 MHz using
a Bruker Avance 500 spectrometer. Chemical shifts are re-
ported in delta (d) units, ppm relative to the center of the
triplet at 77.0 ppm for CDCl3 and 39.5 ppm for DMSO-d6.
13C NMR spectra were routinely run with broadband decou-
pling.
tert-Amyl alcohol (anhydrous, ꢀ99%), which was pur-
chased from Sigma–Aldrich Co., was used as the solvent for
all reactions. Liquid alcohols and arylacetonitriles were
stirred for 24 h over CaH2 and distilled under high vacuum
just before use. Solid alcohols, arylacetonitriles and phos-
phine ligands were treated on a vacuum line with a cold
trap using liquid nitrogen as a coolant before use. Analytical
thin-layer chromatography (TLC) was carried out using
0.2 mm commercial silica gel plates.
3-(4-Isopropylphenyl)-2-phenylpropanamide (4ad): yellow
solid; yield: 214 mg (80%); mp 140–1418C; 1H NMR
(500 MHz, CDCl3): d=7.34–7.25 (m, 5H, ArH), 7.09–7.04
(m, 4H, ArH), 5.29 (br s, 2H, NH2), 3.63 (t, J=7.5 Hz, 1H,
CH), 3.42 (dd, J=13.8 Hz and 8.1 Hz, 1H, CH), 2.96 (dd,
J=13.9 Hz and 6.9 Hz, 1H, CH), 2.84 (sept, J=6.9 Hz, 1H,
CH), 1.21 (d, J=6.9 Hz, 6H, 2xCH3); 13C NMR (125 MHz,
CDCl3): d=175.2, 146.7, 139.6, 136.8, 128.8, 128.8, 128.0,
127.4, 126.3, 54.8, 38.9, 33.6, 24.0; HR-MS-EI (70 eV): m/z=
290.1529, calcd. for C18H21NONa [M+Na]+: 290.1521.
3-(4-Methoxyphenyl)-2-phenylpropanamide (4ae): yellow
solid; yield: 212 mg (83%); mp 161–1628C; 1H NMR
(500 MHz, DMSO-d6): d=7.41 (br s, 1H, NH), 7.35 (d, J=
7.6 Hz, 1H, ArH), 7.28 (t, J=7.4 Hz, 2H, ArH), 7.20 (t, J=
7.1 Hz, 1H, ArH), 7.08 (d, J=8.1 Hz, 2H, ArH), 6.79–6.77
(m, 3H, 2xArH and NH), 3.70–3.67 (m, 4H, CH and CH3),
3.22 (dd, J=13.4 Hz and 9.8 Hz, 1H, CH2), 2.77 (dd, J=
13.6 Hz and 5.9 Hz, 1H, CH2); 13C NMR (125 MHz, DMSO-
d6): d=174.0, 157.5, 140.8, 131.8, 129.8, 128.1, 127.7, 126.6,
113. 5, 54.9, 53.1, 37.8; HR-MS-EI (70 eV): m/z=278.1170,
calcd. for C16H17NO2Na [M+Na]+: 278.1157.
General Procedure for the Synthesis of a-Alkylated
Arylacetamides via Rhodium-Catalyzed Coupling of
Arylacetonitriles with Alcohols under Microwave
Irradiation (Table 2 and Table 3)
3-(4-Fluorophenyl)-2-phenylpropanamide (4af):[10] brown
solid; yield: 214 mg (88%); mp 123–1248C; 1H NMR
(500 MHz, CDCl3): d=7.33–7.25 (m, 5H, ArH), 7.03 (t, J=
6.7 Hz, 2H, ArH), 6.89 (t, J=8.5 Hz, 2H, ArH), 5.39 (br s,
1H, NH), 5.30 (br s, 1H, NH), 3.59 (t, J=7.4 Hz, 1H, CH),
3.50 (dd, J=13.7 Hz and 7.5 Hz, 1H, CH), 2.96 (dd, J=
13.6 Hz and 7.6 Hz, 1H, CH); 13C NMR (125 MHz, CDCl3)
d 175.0, 161.4 (d, JC,F =243.2 Hz), 139.1, 135.1, 130.4 (d,
Nitrile 1 (1 mmol), alcohol 2 (1.1 mmol), [Rh(cod)Cl]2
(0.01 mmol, 1 mol%), PPh3 (0.1 mmol, 0.1 equiv.), KOH
(0.4 equiv.) and tert-amyl alcohol (1 mL) were added to a mi-
crowave vial containing a stirrer bar. The vial was then
placed in a focused, single-mode microwave synthesizer
(Discover CEM, USA) at 1308C for 2 h (300 W, sealed reac-
tion vessel), and was then cooled to ambient temperature.
The reaction mixture was concentrated under vacuum and
purified by flash column chromatography with hexanes/ethyl
acetate to afford the corresponding product.
J
C,F =7.7 Hz), 128.8, 128.0, 127.5, 115.0 (d, JC,F =20.8 Hz),
54.9, 38.5.
3-(4-Chlorophenyl)-2-phenylpropanamide (4ag): yellow
solid; yield: 211 mg (81%); mp 177–1788C; 1H NMR
(500 MHz, DMSO-d6): d=7.43 (br s, 1H, NH), 7.35 (d, J=
7.6 Hz, 2H, ArH), 7.30–7.27 (m, 4H, ArH), 7.22–7.18 (m,
3H, ArH), 6.81 (br s, 1H, NH), 3.71 (dd, J=9.1 Hz and
6.3 Hz, 1H, CH), 3.26 (dd, J=13.6 Hz and 9.3 Hz, 1H,
CH2), 2.85 (dd, J=13.6 Hz and 6.2 Hz, 1H, CH2); 13C NMR
(125 MHz, DMSO-d6): d=173.7, 140.5, 139.0, 130.7, 130.6,
128.2, 128.0, 127.7, 126.7, 52.6, 37.9; HR-MS-EI (70 eV):
m/z=282.0658, calcd. for C15H14NOClNa [M+Na]+:
282.0662.
2,3-Diphenylpropanamide (4aa):[9] brown solid; yield:
1
203 mg (90%); mp 126–1278C; H NMR (500 MHz, CDCl3):
d=7.33–7.24 (m, 5H, ArH), 7.21 (t, J=7.3 Hz, 2H, ArH),
7.15 (t, J=7.3 Hz, 1H, ArH), 7.10 (d, J=7.8 Hz, 2H, ArH),
5.37 (br s, 1H, NH), 5.30 (br s, 1H, NH), 3.64 (t, J=7.5 Hz,
1H, CH), 3.54 (dd, J=13.6 Hz and 7.6 Hz, 1H, CH), 2.99
(dd, J=13.7 Hz and 7.9 Hz, 1H, CH); 13C NMR (125 MHz,
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3-(2-Chlorophenyl)-2-phenylpropanamide (4ah): yellow
solid; yield: 229 mg (88%); mp 179–1808C; 1H NMR
(500 MHz, DMSO-d6): d=7.47 (br s, 1H, NH), 7.40 (d, J=
7.1 Hz, 1H, ArH), 7.35 (d, J=7.4 Hz, 2H, ArH), 7.29 (t, J=
7.3 Hz, 2H, ArH), 7.23–7.20 (m, 4H, ArH), 6.84 (br s, 1H,
NH), 3.82 (t, J=7.3 Hz, 1H, CH), 3.35 (m, 1H, CH), 2.96
(dd, J=13.6 Hz and 5.4 Hz, 1H, CH); 13C NMR (125 MHz,
DMSO-d6): d=173.5, 140.7, 137.2, 133.3, 131.3, 129.2, 128.3,
128.1, 127.6, 126.9, 126.8, 50.6, 36.4; HR-MS-EI (70 eV):
m/z=282.0664, calcd. for C15H14NONaCl [M+Na]+:
282.0662.
22.5, 14.0; HR-MS-EI (70 eV): m/z=242.1527, calcd. for
C14H21NONa [M+Na]+: 242.1521.
3-Phenyl-2-para-tolylpropanamide (4ba): light yellow
solid; yield: 198 mg (83%); mp 138–1398C; 1H NMR
(500 MHz, CDCl3): d=7.21 (t, J=7.32 Hz, 2H, ArH), 7.17–
7.14 (m, 3H, ArH), 7.11 (t, J=6.90 Hz, 4H, ArH), 5.26 (br
s, 2 H, NH2), 3.91 (t, J=7.32 Hz, 1H, CH), 3.53 (dd, J=
7.35 Hz and 7.30 Hz, 1H, CH), 2.98 (dd, J=7.30 Hz and
7.90 Hz, 1H, CH), 2.32 (s, 3H, CH3); 13C NMR (125 MHz,
CDCl3): d=175.41, 139.59, 137.06, 136.33, 129.44, 128.93,
128.20, 127.83, 126.12, 54.31, 39.23, 21.01; HR-MS-EI
(70 eV): m/z=262.1211, calcd. for C16H17NONa [M+Na]+:
262.1208.
2-Phenyl-3-[4-(trifluoromethoxy)phenyl]propanamide
(4ai): light yellow solid; yield: 280 mg (91%); mp 155–
1
3-Phenyl-2-ortho-tolylpropanamide (4ca): yellow solid;
yield: 201 mg (84%); mp 142–1438C; 1H NMR (500 MHz,
CDCl3): d=7.39 (d, J=7.5 Hz, 1H, ArH), 7.26–7.11 (m, 6H,
ArH), 7.07 (d, J=7.1 Hz, 2H, ArH), 5.34 (br s, 1H, NH),
5.20 (br s, 1H, NH), 3.91 (t, J=7.3 Hz, 1H, CH), 3.57 (dd,
J=13.7 Hz and 6.7 Hz, 1H, CH), 2.96 (dd, J=13.6 Hz and
7.9 Hz, 1H, CH), 2.16 (s, 3H, CH3); 13C NMR (125 MHz,
CDCl3): d=175.4, 139.6, 137.6, 136.1, 130.6, 128.9, 128.2,
127.5, 127.3, 126.6, 126.2, 50.4, 38.8, 19.6; HR-MS-EI
(70 eV): m/z=262.1206, calcd. for C16H17NONa [M+Na]+:
262.1208.
1568C; H NMR (500 MHz, CDCl3): d=7.34–7.25 (m, 5H,
ArH), 7.10 (d, J=8.7 Hz, 2H, ArH), 7.05 (d, J=8.2 Hz, 2H,
ArH), 5.36 (br s, 1H, NH), 5.30 (br s, 1H, NH), 3.60 (t, J=
7.3 Hz, 1H, CH), 3.54 (dd, J=13.4 Hz and 7.4 Hz, 1H, CH),
2.98 (dd, J=13.5 Hz and 7.3 Hz, 1H, CH); 13C NMR
(125 MHz, CDCl3): d=174.6, 147.7, 139.0, 138.2, 130.3,
128.9, 128.0, 127.7, 120.8, 120.4 (q, JCÀF =255.5 Hz), 54.7,
38.6; HR-MS-EI (70 eV): m/z=332.0878, calcd. for
C16H14NO2F3Na [M+Na]+: 332.0874.
3-(Naphthalen-1-yl)-2-phenylpropanamide (4aj): brown
solid; yield: 240 mg (87%); mp 150–1518C; 1H NMR
(500 MHz, CDCl3): d=8.06 (d, J=8.1 Hz, 1H, ArH), 7.86
(d, J=7.6 Hz, 1H, ArH), 7.69 (d, J=8.1 Hz, 1H, ArH), 7.51
(m, 2H, ArH), 7.32–7.26 (m, 6H, ArH), 7.17 (d, J=6.7 Hz,
1H, ArH), 5.27 (br s, 1H, NH), 5.21 (br s, 1H, NH), 4.06
(dd, J=13.8 Hz and 7.5 Hz, 1H, CH2), 3.82 (t, J=7.0 Hz,
1H, CH), 3.42 (dd, J=14.0 Hz and 6.7 Hz, 1H, CH2);
13C NMR (125 MHz, CDCl3): d=175.0, 139.7, 135.3, 133.9,
131.6, 128.9, 128.8, 127.9, 127.5, 127.4, 127.1, 126.0, 125.4,
123.4, 53.5, 36.5; HR-MS-EI (70 eV): m/z=298.1201, calcd.
for C19H17NONa [M+Na]+: 298.1208.
2-(4-Methoxyphenyl)-3-phenylpropanamide
(4da):[11]
1
yellow solid; yield: 205 mg (80%); mp 162–1648C; H NMR
(500 MHz, CDCl3): d=7.22–7.08 (m, 5H, ArH), 7.09 (d, J=
7.8 Hz, 2H, ArH), 6.84 (d, J=8.5 Hz, 2H, ArH), 5.38 (br s,
1H, NH), 5.30 (br s, 1H, NH), 3.79 (s, 3H, OCH3), 3.59 (t,
J=7.4 Hz, 1H, CH), 3.51 (dd, J=13.6 Hz and 7.4 Hz, 1H,
CH), 2.96 (dd, J=13.6 Hz and 7.7 Hz, 1H, CH); 13C NMR
(125 MHz, CDCl3): d=175.6, 158.8, 139.6, 131.4, 129.1,
129.0, 128.2, 126.1, 114.1, 55.2, 53.9, 39.4.
2-(3,4-Dimethoxyphenyl)-3-phenylpropanamide
(4ea):
light yellow solid; yield: 260 mg (91%); mp 100–1018C;
1H NMR (500 MHz, CDCl3): d=7.22 (t, J=7.3 Hz, 2H,
ArH), 7.16 (t, J=7.3 Hz, 1H, ArH), 7.09 (d, J=7.0 Hz, 2H,
ArH), 6.79–6.78 (m, 3H, ArH), 5.31 (br s, 2H, NH2), 3.86 (s,
3H, OCH3), 3.84 (s, 3H, OCH3), 3.58 (t, J=7.4 Hz, 1H,
CH), 3.50 (dd, J=13.8 Hz and 7.3 Hz, 1H, CH), 2.98 (dd,
J=13.6 Hz and 7.6 Hz, 1H, CH); 13C NMR (125 MHz,
CDCl3): d=175.4, 149.0, 148.3, 139.5, 131.8, 129.0, 128.2,
126.2, 120.3, 111.1, 110.9, 55.83, 55.80, 54.3, 39.4; HR-MS-EI
(70 eV): m/z=308.1269, calcd. for C17H19NO3Na [M+Na]+:
308.1263.
3-(Ferrocenemethyl)-2-phenylpropanmide (4ak): brown
solid; yield: 264 mg (79%); mp 117–1188C; 1H NMR
(500 MHz, CDCl3): d=7.32 (t, J=7.3 Hz, 2H, ArH), 7.27–
7.25 (m, 3H, ArH), 5.26 (br s, 2H, NH), 4.10 (br s, 1H, fer-
rocene H), 4.08 (s, 5H, ferrocene H), 4.01 (br s, 1H, ferro-
cene H), 3.95 (br s, 1H, ferrocene H), 3.78 (br s, 1H, ferro-
cene H), 3.43(t, J=7.17 Hz, 1H, CH), 3.28 (dd, J=7.25 Hz
and 7.3 Hz, 1H, CH2), 2.77 (dd, J=7.3 Hz and 7.45 Hz, 1H,
CH2); 13C NMR (125 MHz, CDCl3): d=175.3, 139.7, 128.7,
127.8, 127.4, 85.9, 68.9, 68.8, 68.6, 67.4, 67.3, 55.3, 33.9; HR-
MS-EI (70 eV): m/z=356.0721, calcd. for C19H19FeNONa
[M+Na]+: 356.0714.
2-(4-Fluorophenyl)-3-phenylpropanamide (4fa): yellow
solid; yield: 224 mg (92%); mp 150–1518C; 1H NMR
(500 MHz, CDCl3): d=7.26–7.21 (m, 4H, ArH), 7.17 (t, J=
7.2 Hz, 1H, ArH), 7.08 (d, J=7.1 Hz, 2H, ArH), 7.00 (t, J=
8.6 Hz, 2H, ArH), 5.39 (br s, 1H, NH), 5.29 (br s, 1H, NH),
3.61 (t, J=7.6 Hz, 1H, CH), 3.49 (dd, J=13.7 Hz and
7.6 Hz, 1H, CH), 2.96 (dd, J=13.6 Hz and 7.6 Hz, 1H, CH);
2-Phenylhexanamide (4al):[10] light yellow solid; yield:
141 mg (74%); mp 94–958C; 1H NMR (500 MHz, CDCl3):
d=7.36–7.26 (m, 5H, ArH), 5.41 (br s, 1H, NH), 5.34 (br s,
1H, NH), 3.37 (t, J=7.3 Hz, 1H, CH), 2.19–2.11 (m, 1H,
CH), 1.82–1.75 (m, 1H, CH), 1.38–1.13 (m, 4H, 2ꢂCH2),
0.86 (t, J=7.1 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3):
d=176.4, 140.0, 128.8, 127.9, 127.2, 52.8, 32.6, 29.8, 22.5,
13.9.
13C NMR (125 MHz, CDCl3): d=174.9, 162.1 (d, JC,F
244.7 Hz), 139.1, 135.0, 129.6 (d, JC,F =8.1 Hz), 128.9, 128.3,
=
126.4, 115.6 (d,
JC,F =21.2 Hz), 54.0, 39.6; HR-MS-EI
(70 eV): m/z=266.0956, calcd. for C15H14NOFNa [M+Na]+:
266.0957.
2-Phenyloctanamide (4am): white solid; yield: 167 mg
1
(76%); mp 85–868C; H NMR (500 MHz, CDCl3): d=7.36–
7.27 (m, 5H, ArH), 5.40 (br s, 1H, NH), 5.34 (br s, 1H,
NH), 3.37 (t, J=7.6 Hz, 1H, CH), 2.18–2.11 (m, 1H, CH2),
1.81–1.74 (m, 1H, CH2), 1.35–1.14 (m, 8H, 4ꢂCH2), 0.85 (t,
J=7.0 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3): d=
176.3, 140.0, 128.8, 127.9, 127.2, 52.8, 32.9, 31.6, 29.1, 27.6,
2-(3-Fluorophenyl)-3-phenylpropanamide (4ga): yellow
solid; yield: 216 mg (89%); mp 147–1488C; 1H NMR
(500 MHz, DMSO-d6): d=7.47 (br s, 1H, NH), 7.35–7.15
(m, 8H, ArH), 7.04 (t, J=7.9 Hz, 1H, ArH), 6.86 (br s, 1H,
NH), 3.79 (t, J=7.1 Hz, 1H, CH), 3.27 (dd, J=13.5 Hz and
8
asc.wiley-vch.de
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Direct Coupling of Arylacetonitriles and Primary Alcohols
9.8 Hz, 1H, CH), 2.86 (dd, J=13.3 Hz and 5.9 Hz, 1H, CH);
(0.8 equiv.) and tert-amyl alcohol (1 mL) were added to a mi-
crowave vial containing a stirrer bar. The vial was then
placed in a focused, single-mode microwave synthesizer
(Discover CEM, USA) at 1308C for 2 h (300 W, sealed reac-
tion vessel), and was then cooled to ambient temperature.
The reaction mixture was concentrated under vacuum and
purified by flash column chromatography with hexanes/ethyl
acetate to afford the corresponding product.
13C NMR (125 MHz, DMSO-d6): d=173.5, 162.0 (d, JC,F
241.6 Hz), 143.5 (d, JC,F =7.2 Hz), 139.6, 130.0 (d, JC,F
=
=
8.2 Hz), 128.8, 128.1, 126.0, 124.0, 114.5 (d, JC,F =20.8 Hz),
113.4 (d, JC,F =20.8 Hz), 52.4, 38.5; HR-MS-EI (70 eV):
m/z=266.0952, calcd. for C15H14NOFNa [M+Na]+:
266.0957.
2-(4-Chlorophenyl)-3-phenylpropanamide (4ha): yellow
solid; yield: 215 mg (83%); mp 165–1668C; 1H NMR
(500 MHz, DMSO-d6): d=7.47–7.16 (m, 10H, 9ꢂArH and
NH), 6.86 (br s, 1H, NH), 3.76 (br s, 1H, CH), 3.27 (br s,
1H, CH), 2.85 (br s, 1H, CH); 13C NMR (125 MHz, DMSO-
d6): d=173.6, 139.6, 131.3, 129.6, 128.8, 128.1, 127.7, 126.6,
126.0, 52.0, 38.5; HR-MS-EI (70 eV): m/z=282.0652, calcd.
for C15H14NOClNa [M+Na]+ :282.0662.
3-[3-(2-Amide-2-phenylethyl)phenyl]-2-phenylpropanam-
AHCTUNGTREGiNNNU de (4an): white solid; yield: 322 mg (86%); mp 180–1818C;
1H NMR (500 MHz, DMSO-d6): d=7.42–6.79 (m, 18H,
ArH and NH2), 3.72 (s, 2H, 2ꢂCH), 3.25 (s, 2H, 2ꢂCH),
2.76 (s, 2H, 2ꢂCH); 13C NMR (125 MHz, DMSO-d6): d=
174.0, 140.8, 139.6, 129.4, 128.1, 127.7, 126.6, 126.4, 52.6,
38.7; HR-MS-EI (70 eV): m/z=395.1742, calcd. for
C24H24N2O2Na [M+Na]+: 395.1735.
3-Phenyl-2-[3-(trifluoromethyl)phenyl]propanamide (4ia):
1
brown solid; yield: 247 mg (84%); mp 123–1258C; H NMR
3-{3-[2-Amide-2-(4-methyl)phenylethyl]phenyl}-2-(4-
methyl)propanamide (4bn): light yellow solid; yield: 319 mg
(500 MHz, DMSO-d6): d=7.68–7.54 (m, 5H, 4ꢂArH and
NH), 7.22–7.18 (m, 5H, ArH), 6.91 (br s, 1H, NH), 3.89 (br
s, 1H, CH), 3.35 (br s, 1H, CH), 2.89 (br s, 1H, CH);
13C NMR (125 MHz, DMSO-d6): d=173.3, 142.0, 139.5,
131.9, 129.2, 128.9 (q, JC,F =30.8 Hz), 128.8, 128.1, 126.1,
124.3 (q, JC,F =271.0 Hz), 124.2, 123.4, 52.4, 38.5; HR-MS-EI
(70 eV): m/z=316.0929, calcd. for C16H14NOF3Na [M+
Na]+: 316.0925.
3-Phenyl-2-[4-(trifluoromethoxy)phenyl]propanamide
(4ja): yellow solid; yield: 279 mg (90%); mp 160–1618C;
1H NMR (500 MHz, DMSO-d6): d=7.49–7.17 (m, 10H, 9ꢂ
ArH and NH), 6.87 (br s, 1H, NH), 3.82 (br s, 1H, CH),
3.30 (br s, 1H, CH), 2.85 (d, J=7.9 Hz, 1H, CH); 13C NMR
(125 MHz, DMSO-d6): d=173.6, 147.1, 140.1, 139.7, 129.5,
128.8, 128.1, 126.0, 120.8, 120.1 (q, JC,F =254.4 Hz), 52.0,
38.6; HR-MS-EI (70 eV): m/z=332.0867, calcd. for
C16H14NO2F3Na [M+Na]+: 332.0874.
1
(80%); mp 188–1898C; H NMR (500 MHz, DMSO-d6): d=
7.34 (br s, 2H, 2xNH), 7.22 (d, J=7.5 Hz, 4H, ArH), 7.09–
7.02 (m, 6H, ArH), 6.91 (d, J=7.0 Hz, 2H, ArH), 6.73 (br s,
2H, 2ꢂNH), 3.69 (t, J=7.1 Hz, 2H, 2ꢂCH), 3.21 (dd, J=
13.2 Hz and 9.8 Hz, 2H, 2ꢂCH), 2.73 (dd, J=13.9 Hz and
5.9 Hz, 2H, 2ꢂCH), 2.25 (s, 6H, 2ꢂCH3); 13C NMR
(125 MHz, DMSO-d6): d=174.2, 139.7, 137.8, 135.5, 129.4,
128.7, 127.7, 127.6, 126.4, 52.3, 38.7, 20.6; HR-MS-EI
(70 eV): m/z=423.2056, calcd. for C26H28N2O2Na [M+Na]+:
423.2048.
3-{3-[2-Amide-2-(4-fluoro)phenylethyl]phenyl}-2-(4-fluo-
ro)propanamide (4fn): yellow solid; yield: 339 mg 83%); mp
192–1938C; 1H NMR (500 MHz, DMSO-d6): d=7.41–7.35
(m, 6H, 4ꢂArH and 2ꢂNH), 7.10–7.05 (m, 6H, ArH), 6.91
(s, 2H, ArH), 6.80 (br s, 2H, 2ꢂNH), 3.73 (s, 2H, 2ꢂCH),
3.21 (s, 2H, 2ꢂCH), 2.76 (s, 2H, 2ꢂCH); 13C NMR
(125 MHz, DMSO-d6): d=174.0, 161.1 (d, JC,F =240.5 Hz),
139.4, 136.9, 129.5 (d, JC,F =5.8 Hz), 129.4, 127.8, 126.5, 114.8
(d, JC,F =20.9 Hz), 51.8, 38.8; HR-MS-EI (70 eV): m/z=
431.1553, calcd. for C24H22N2O2F2Na [M+Na]+: 431.1547.
2-(Naphthalen-1-yl)-3-phenylpropanamide (4ka): light
1
yellow solid; yield: 226 mg (82%); mp 132–1338C; H NMR
(500 MHz, CDCl3): d=8.07 (d, J=5.2 Hz, 1H, ArH), 7.89–
7.78 (m, 2H, ArH), 7.53–7.43 (m, 4H, ArH), 7.26–7.13 (m,
5H, ArH), 5.27 (m, 2H, NH2), 4.40 (br s, 1H, CH), 3.74 (br
s, 1H, CH), 3.18 (br s, 1H, CH); 13C NMR (125 MHz,
CDCl3): d=175.2, 139.9, 135.2, 134.1, 131.2, 129.2, 128.9,
128.3, 128.2, 126.6, 126.2, 126.1, 125.8, 125.6, 123.0, 51.0,
38.4; HR-MS-EI (70 eV): m/z=298.1207, calcd. for
C19H17NONa [M+Na]+: 298.1208.
Condensation Between 2-Phenylacetonitrile and
Benzaldehyde [Scheme 4, Eq. (1)]
Phenylacetonitrile 1a (1 mmol), benzaldehyde 5 (1.1 mmol),
KOH (0.4 equiv.) and tert-amyl alcohol (1 mL) were added
to a microwave vial containing a stirrer bar. The vial was
then placed in a focused, single-mode microwave synthesizer
(Discover CEM, USA) at 1308C for 2 h (300 W, sealed reac-
tion vessel), and was then cooled to ambient temperature.
The reaction mixture reaction was concentrated under
vacuum and purified by flash column chromatography with
hexanes/ethyl acetate to afford the corresponding product 6.
(Z)-2,3-Diphenylacrylonitrile (6):[5b] white solid; yield:
183 mg (89%); mp 80–818C; 1H NMR (500 MHz, CDCl3):
d=7.88 (d, J=7.4 Hz, 2H, ArH), 7.68 (d, J=7.7 Hz, 2H,
ArH), 7.54 (s, 1H, CH), 7.51–7.36 (m, 6H, ArH); 13C NMR
(125 MHz, CDCl3): d=142.1, 134.3, 133.6, 130.4, 129.1,
129.06, 128.9, 128.8, 125.9, 117.9, 111.5.
2-(Naphthalen-2-yl)-3-phenylpropanamide (4la): light
1
yellow solid; yield: 243 mg (88%); mp 148–1498C; H NMR
(500 MHz, CDCl3): d=7.82–7.70 (m, 4H, ArH), 7.48–7.44
(m, 3H, ArH), 7.26–7.12 (m, 5H, ArH), 5.41 (br s, 1H,
NH), 5.34 (br s, 1H, NH), 3.81 (t, J=7.0 Hz, 1H, CH), 3.63
(dd, J=13.5 Hz and 7.5 Hz, 1H, CH), 3.10 (dd, J=13.4 Hz
and 7.5 Hz, 1H, CH); 13C NMR (125 MHz, CDCl3): d=
175.0, 139.4, 136.8, 133.4, 132.6, 129.0, 128.6, 128.3, 127.7,
127.6, 127.0, 126.3, 126.2, 126.0, 125.8, 54.9, 39.2; HR-MS-EI
(70 eV): m/z=298.1210, calcd. for C19H17NONa [M+Na]+:
298.1208.
General Procedure for the Rhodium-Catalyzed
Coupling of Arylacetonitriles with a Diol under
Microwave Irradiation (Scheme 3)
Nitrile 1 (2.2 mmol), alcohol 2n (1 mmol), [Rh(cod)Cl]2
(0.02 mmol, 2 mol%), PPh3 (0.2 mmol, 0.2 equiv.), KOH
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
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FULL PAPERS
Feng Li et al.
35, 695–705; c) C. J. Li, B. M. Trost, Proc. Natl. Acad.
Sci. USA 2008, 105, 13197–13202; d) P. Anastas, N.
Eghbali, Chem. Soc. Rev. 2010, 39, 301–312.
Hydrogen Transfer between (Z)-2,3-Diphenyl-
acrylonitrile and Benzyl Alcohol [Scheme 4, Eq. (2)]
Nitrile 6 (1 mmol), 2a (1.1 mmol), [Rh(cod)Cl]2 (0.01 mmol,
1 mol%), PPh3 (0.1 mmol, 0.1 equiv.), KOH (0.4 equiv.) and
tert-amyl alcohol (1 mL) were added to a microwave vial
containing a stirrer bar. The vial was then placed in a fo-
cused, single-mode microwave synthesizer (Discover CEM,
USA) at 1308C for 2 h (300 W, sealed reaction vessel), and
was then cooled to ambient temperature. The reaction mix-
ture was concentrated under vacuum and purified by flash
column chromatography with hexanes/ethyl acetate to
afford the corresponding product 3aa.
[2] For selected reviews about the hydrogen autotransfer
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2,3-Diphenylpropanenitrile (3aa):[5d] white solid; yield:
188 mg (91%); mp 49–508C; 1H NMR (500 MHz, CDCl3):
d=7.38–7.24 (m, 8H, ArH), 7.14 (t, J=4.0 Hz, 2H, ArH),
4.00 (q, J=5.0 Hz, 1H, CH), 3.22–3.11 (m, 2H, CH2);
13C NMR (125 MHz, CDCl3): d=136.2, 135.2, 129.2, 129.0,
128.6, 128.13, 127.4, 127.3, 120.3, 42.1, 39.7.
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761–765; Angew. Chem. 2014, 126, 780–784; o) S.
Ogawa, Y. Obora, Chem. Commun. 2014, 50, 2491–
2493; p) D. Wang, K. Zhao, C. Xu, H. Miao, Y. Ding,
ACS Catal. 2014, 4, 3910–3918.
Hydration of (Z)-2,3-Diphenylacrylonitrile [Scheme
4, Eq. (3)]
Nitrile 6 (1 mmol), H2O (1 mmol, 1 equiv.), [Rh(cod)Cl]2
(0.01 mmol, 1 mol%), PPh3 (0.1 mmol, 0.1 equiv.), KOH
(0.4 equiv.) and tert-amyl alcohol (1 mL) were added to a mi-
crowave vial containing a stirrer bar. The vial was then
placed in a focused, single-mode microwave synthesizer
(Discover CEM, USA) at 1308C for 2 h (300 W, sealed reac-
tion vessel), and was then cooled to ambient temperature.
1
No hydrated product was found from the H NMR spectrum
of crude reaction mixture.
Hydration of (Z)-2,3-Diphenylpropanenitrile [Scheme
4, Eq.(4)]
Nitrile 3aa (1 mmol), H2O (1 mmol, 1 equiv), [Rh(cod)Cl]2
(0.01 mmol, 1 mol%), PPh3 (0.1 mmol, 0.1 equiv.), KOH
(0.4 equiv.) and tert-amyl alcohol (1 mL) were added to a mi-
crowave vial containing a stirrer bar. The vial was then
placed in a focused, single-mode microwave synthesizer
(Discover CEM, USA) at 1308C for 2 h (300 W, sealed reac-
tion vessel), and was then cooled to ambient temperature.
The reaction mixture was concentrated under vacuum and
purified by flash column chromatography with hexanes/ethyl
acetate to afford the corresponding product 4aa as a brown
solid; yield: 202 mg (90%).
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Acknowledgements
The financial support of the National Natural Science Foun-
dation of China (No. 21272115) and Fundamental Research
Funds for the Central Universities (No. 30920130111005) is
greatly appreciated.
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12 Direct Coupling of Arylacetonitriles and Primary Alcohols
to a-Alkylated Arylacetamides with Complete Atom
Economy Catalyzed by a Rhodium Complex–
Triphenylphosphine–Potassium Hydroxide System
Adv. Synth. Catal. 2015, 357, 1 – 12
Feng Li,* Xiaoyuan Zou, Nana Wang
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These are not the final page numbers!