Palladium-catalyzed carbonylative synthesis of α,β-unsaturated amides from aryl azides and alkenylaluminum reagent

Article abstract of DOI:10.1016/j.jcat.2020.01.017

In this work, an interesting procedure for the synthesis of α,β-unsaturated amides from aryl azides and alkenylaluminum reagent has been developed. With palladium as the catalyst and XPhos as the ligand under carbon monoxide pressure, the desired α,β-unsaturated amides were isolated in good to excellent yields with good functional group tolerance. Remarkably, this procedure also represents an example on addition of organometallic reagent to isocyanates for α,β-unsaturated amides synthesis.

Full text of DOI:10.1016/j.jcat.2020.01.017

Journal of Catalysis 383 (2020) 160–163
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Journal of Catalysis
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Priority Communication
Palladium-catalyzed carbonylative synthesis of
from aryl azides and alkenylaluminum reagent
a,b-unsaturated amides
⇑
Bo Chen, Xiao-Feng Wu
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of China
Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Strabe 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
In this work, an interesting procedure for the synthesis of a,b-unsaturated amides from aryl azides and
Received 31 October 2019
Revised 13 January 2020
Accepted 14 January 2020
alkenylaluminum reagent has been developed. With palladium as the catalyst and XPhos as the ligand
under carbon monoxide pressure, the desired ,b-unsaturated amides were isolated in good to excellent
yields with good functional group tolerance. Remarkably, this procedure also represents an example on
addition of organometallic reagent to isocyanates for ,b-unsaturated amides synthesis.
Ó 2020 Elsevier Inc. All rights reserved.
a
a
Keywords:
Palladium catalyst
Carbonylation
a,b-Unsaturated amides
Aryl Azides
Alkenylaluminum reagent
Carbonylative coupling
1. Introduction
aminocarbonylation of styrenes with nitroarenes for the synthesis
of ,b-unsaturated amides [9]. Additionally, palladium-catalyzed
aminocarbonylation of enol triflates or iodoalkenes has been pro-
ven as an potent procedure for ,b-unsaturated amides synthesis
as well [10]. Although significant progresses have been achieved
in ,b-unsaturated amides synthesis, new procedure is always
a
a
,b-Unsaturated amide and its derivatives are important struc-
tural motifs due to their wide occurrence in natural products and
also many other known biological activities [1,2]. Additionally,
a
a,
b-unsaturated amides are useful synthetic intermediates for vari-
ous potent organic transformations as well [3]. Many methodolo-
gies for their preparation have been developed in recent years,
because of their recognized potent applications in pharmaceuticals
and synthetic chemistry [4]. The traditional method for preparing
a
attractive as it can give the possibility to start from different
substrates. Herein, we report a new method for the synthesis of
a,b-unsaturated amides which is achieved by palladium-
catalyzed carbonylation of aryl azides and alkenylaluminum
a,b-unsaturated amides was based on reacting of amines with a,
reagent.
b-unsaturated carboxylic acid in the presence of activating
reagents [5]. Recently, Martin and co-workers developed a novel
protocol for the hydroamidation of alkynes with isocyanates
recently. Alkyl bromides have been used as hydride sources here.
The method turns parasitic b-hydride elimination into a strategic
advantage, rapidly affording a,b-unsaturated amides in good yields
[6]. Transition-metal catalyzed carbonylation procedures based on
using alkenes and alkynes as the substrates have also been devel-
The initial investigation was carried out with azidobenzene and
(E)-diisobutyl(oct-1-en-1-yl)aluminum which was prepare from
oct-1-yne with diisobutylaluminum hydride (DIBAL-H) as the sub-
strates. To our delight, the target (E)-N-phenylnon-2-enamide can
be successfully obtained in 73% yield with Pd/C as the catalyst and
XPhos as the ligand in THF at 80 °C for 16 h under CO pressure
(Table 1, entry 1). The yield of the target product can be further
improved by using Pd(OAc)2 as the catalyst (Table 1, entry 2). Sub-
sequently, with Pd(OAc)2 as the catalyst, different phosphine
ligands were tested (Table 1, entries 3–8). XPhos was found still
to be the best ligand for this reaction, which may due to its promis-
ing properties on electron donation and sterically hindrance. Then
a set of solvents were tested, the reaction efficiency decreased sig-
nificantly in these cases and THF is the optimal solvent (Table 1,
entries 9–11). The reaction temperature was varied as well;
oped for
described a chemo- and regioselective direct aminocarbonylation
of alkynes and aminophenols to form hydroxy-substituted ,b-
a,b-unsaturated amides preparation [7–9]. Alper’s group
a
unsaturated amides in good to excellent yields [8]. Our group
developed a procedure on palladium-catalyzed selective oxidative
⇑
Corresponding author.
E-mail address: Xiao-Feng.Wu@catalysis.de (X.-F. Wu).
https://doi.org/10.1016/j.jcat.2020.01.017
0021-9517/Ó 2020 Elsevier Inc. All rights reserved.

B. Chen, X.-F. Wu / Journal of Catalysis 383 (2020) 160–163
161
Table 1
Selected results of the optimization of the reaction conditions.a
Entry
Catalyst
Ligand
Solvent
Yield %b
1
2
3
4
5
6
7
8
Pd/C
XPhos
XPhos
PPh3
THF
THF
THF
THF
THF
THF
THF
THF
Toluene
1,4-dioxane
DCE
THF
THF
73
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
82(76c)
trace
trace
65
DPPP
DPEphos
DPPM
DPPE
Xantphos
XPhos
XPhos
XPhos
XPhos
XPhos
23
42
77
21
53
7
65
75
9
10
11
12d
13e
a
b
c
Reaction conditions: 1a (0.5 mmol), 2a (0.7 mmol in hexane), catalyst (2 mol %), ligand (2 mol %), solvent (1.0 mL), 10 bar CO, 80 °C, 16 h.
NMR yield.
Isolated yield.
60 °C.
d
e
100 °C.
inferior results were observed at 60 °C or 100 °C (Table 1, entries
12–13). Here, it is also important to mention that 65% yield of
the target product can be obtained even under 1 bar of CO. How-
ever, due to the low boiling point of THF, we decided continual
our studies with 10 bar of CO in order to avoid the leaching of
solvent.
With the optimal reaction conditions in hand, we explored the
substrates scope of this carbonylative reaction. At first, we tested
the generality of substituted phenyl azide substrates. As shown
in Scheme 1, azidobenzene with electron-donating or
-withdrawing substituents can be well tolerated, and delivering
the desired products in good to excellent yields (3aa-3ia, 3la-
3na). Then, we tried substrates with functional groups including
alkenyl, cyano, which may be incompatible with aluminum
reagents. Fortunately, for these compounds, the reaction could also
give the expected products in 64% and 84% yields, respectively (3ja,
3 ka). Notably, phenyl ether-, phenyl sulfide-, phenyl- substituted
azidobenzenes were also well tolerated in this transformation and
delivered the corresponding
a,b-unsaturated amides in 74%, 84%
and 76% yields, respectively (3oa-3qa). Additionally, the reaction
with 1-azidonaphthalene also proceeded smoothly and gave the
target products in 75% yield (3ra).
Subsequently, different types of alkenylaluminum reagents for
this reaction were tested (Scheme 2). Several aliphatic alkenylalu-
minums were prepared from the corresponding aliphatic alkynes
with DIBAL-H proceeded well under our conditions to afford the
desired products in good to excellent yield (3ab-3ah). Interest-
ingly, diene aluminum compound can be successfully transformed
in this reaction and gave the target product in 76% yield (3ai). Aro-
matic alkenylaluminums can also work well in this reaction, good
yields of the corresponding products can be isolated (3aj-3am). In
the case of using indole-substituted alkenylaluminum as the sub-
strate, 54% of the desired product was isolated (3an).
Concerning the reaction pathway, on the basis of our results and
the literatures,[11] a possible reaction mechanism is proposed and
shown in Scheme 3. First, from azidobenzene as the substrate, the
palladium-nitrene species A is formed simultaneously with the
release of N2. Subsequent insertion of CO into A occurred to give
the intermediate B. After reductive elimination, the isocyanate will
be afforded and the released palladium species which is ready for
Scheme 1. Synthesis of
a
,b-Unsaturated Amides from Aryl Azides. Reaction
conditions: aryl azides (0.5 mmol), alkenylaluminum reagent 2a (0.7 mmol in
hexane), Pd(OAc)2 (2 mol %), XPhos (2 mol %), THF (1.0 mL), 10 bar CO, 80 °C, 16 h,
isolated yield.
the next catalytic cycle. Finally, the reaction of isocyanate with
alkenylaluminum reagent produces the desired final product 3aa.
In conclusion, we have developed an interesting procedure for
the synthesis of
a,b-unsaturated amides started from aryl azides

162
B. Chen, X.-F. Wu / Journal of Catalysis 383 (2020) 160–163
S. Buchholz, and S. Schareina (all in LIKAT) is gratefully
acknowledged.
General procedure
Under an Argon atmosphere, a 4 mL screwcap vial was charged
with Pd(OAc)2 (2 mol %), XPhos (2 mol %), azidobenzene
(0.5 mmol), THF (1 mL) and an oven-dried stirring bar, then
injected alkenylaluminum solution which are prepared from the
corresponding alkynes with DIBAL-H. The vial was closed by a
Teflon septum and a phenolic cap and connected to the atmo-
sphere through a needle. Then the vial was fixed in an alloy plate
and put into Parr 4560 series autoclave (300 mL). At room temper-
ature, the autoclave is flushed with carbon monoxide for three
times and 10 bar of carbon monoxide was charged. The autoclave
was placed on a heating plate equipped with magnetic stirring
and an aluminum block. The reaction was heated at 80 oC for 16
hours. Afterwards, the autoclave was cooled to room temperature
and the pressure carefully released. After removal of solvent under
reduced pressure, pure product was obtained by column chro-
matography on silica gel (eluent: heptane/ethyl acetate 5:1).
Appendix A. Supplementary material
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.jcat.2020.01.017.
Scheme 2. Synthesis of a,b-Unsaturated Amides from Alkenylaluminum reagents.
References
Reaction conditions: phenyl azides (0.5 mmol), alkenylaluminum reagent
2
(0.7 mmol in hexane), Pd(OAc)2 (2 mol %), XPhos (2 mol %), THF (1.0 mL), 10 bar
CO, 80 °C, 16 h, isolated yield.
[1] (a) R.J. Andersen, J.E. Coleman, E. Piers, D.J. Wallace, Tetrahedron Lett. 38
(1997) 317–320;
(b) C. Marrano, P. de Macédo, J.W. Keillor, Bioorg. Med. Chem. 9 (2001) 1923–
1928;
(c) R. Hitayezu, M.M. Baakdah, J. Kinnin, K. Henderson, A.J. Tsopmo, J. Cereal
Sci. 63 (2015) 35–40;
(d) S. Son, B.A. Lewis, J. Agric. Food Chem. 50 (2002) 468–472;
(e) L. Dai, C. Zang, S. Tian, W. Liu, S. Tan, Z. Cai, T. Ni, M. An, R. Li, Y. Gao, D.
Zhang, Y. Jiang, Med. Chem. Lett. 25 (2015) 34–37.
[2] (a) K.S. Putt, V. Nesterenko, R.S. Dothager, P.J. Hergenrother, ChemBioChem 7
(2006) 1916–1922;
(b) T.W. Schultz, J.W. Yarbrough, S.K. Koss, Cell Biol. Toxicol. 22 (2006) 339–
349.
[3] (a) M.J. Caulfield, G.G. Qiao, D.H. Solomon, Chem. Rev. 102 (2002) 3067–3083;
(b) X. Mu, T. Wu, H.-Y. Wang, Y.-L. Guo, G.S. Liu, J. Am. Chem. Soc. 134 (2012)
878–881;
(c) J.-H. Fan, W.-T. Wei, M.-B. Zhou, R.-J. Song, J.-H. Li, Angew. Chem., Int. Ed.
53 (2014) 6650–6654;
(d) K. Liu, L.-C. Sui, Q. Jin, D.-Y. Li, P.-N. Liu, Org. Chem. Front. 4 (2017) 1606–
1610;
(e) Z.-Y. He, J.-Y. Guo, S.-K. Tian, Adv. Synth. Catal. 360 (2018) 1544–1548.
[4] (a) J.M. Concellón, J.A. Pérez-Andrés, H. Rodríguez-Solla, Angew. Chem., Int. Ed.
39 (2000) 2773–12275;
Scheme 3. Proposed reaction mechanism.
(b) X.-R. Song, B. Song, Y.-F. Qiu, Y.-P. Han, Z.-H. Qiu, X.-H. Hao, X.-Y. Liu, Y.-M.
Liang, J. Org. Chem. 79 (2014) 7616–7625;
(c) Z. Liu, F. Huang, P. Wu, Q. Wang, Z. Yu, J. Org. Chem. 83 (2018) 5731–5750;
(d) X.-R. Song, B. Song, Y.-F. Qiu, Y.-P. Han, Z.-H. Qiu, X.-H. Hao, X.-Y. Liu, Y.-M.
Liang, J. Org. Chem. 79 (2014) 7616–7625.
and alkenylaluminum reagents. In the presence of palladium cata-
lyst under carbon monoxide pressure, the desired a,b-unsaturated
amides were isolated in good to excellent yields with good func-
tional group tolerance. Remarkably, this work also represents an
example on the addition of organometallic reagent to isocyanates.
[5] (a) C.A.G.N. Montalbetti, V. Falque, Tetrahedron 61 (2005) 10827–10852;
(b) E. Valeur, M. Bradley, Chem. Soc. Rev. 38 (2009) 606–631;
(c) V.J. Pattabiraman, J.W. Bode, Nature 480 (2011) 471–479;
(d) C.L. Allen, J.M. Williams, Chem. Soc. Rev. 40 (2011) 3405–3415;
(e) J.W. Bode, Top. Organomet. Chem. 44 (2012) 13–34;
(f) H. Lundberg, F. Tinnis, N. Selander, H. Adolfsson, Chem. Soc. Rev. 43 (2014)
2714–2742;
Declaration of Competing Interest
(g) R.M. de Figueiredo, J.-S. Suppo, J.-M. Campagne, Chem. Rev. 116 (2016)
12029–12122;
(h) A.O. Porras, D. Gamba-Sánchez, J. Org. Chem. 81 (2016) 11548–11555.
[6] X.-Q. Wang, M. Nakajima, E. Serrano, R. Martin, J. Am. Chem. Soc. 138 (2016)
15531–15534.
[7] (a) R. Shi, H. Zhang, L. Lu, P. Gan, Y. Sha, H. Zhang, Q. Liu, M. Beller, A. Lei,
Chem. Commun. 51 (2015) 3247–3250;
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
(b) J.H. Park, S.Y. Kim, S.M. Kim, Y.K. Chung, Org. Lett. 9 (2007) 2465–2468;
(c) T. Fujihara, Y. Katafuchi, T. Iwai, J. Terao, Y. Tsuji, J. Am. Chem. Soc. 132
(2010) 2094–2098;
Acknowledgment
(d) B. El Ali, A.M. El-Ghanam, M. Fettouhi, J. Tijani, Tetrahedron Lett. 41 (2000)
5761–5764;
(e) U. Matteoli, A. Scrivanti, V. Beghetto, J. Mol. Catal. A: Chem. 213 (2004)
C.B. thanks the Chinese Scholarship Council (CSC) for financial
support. The analytical support of Dr W. Baumann, Dr C. Fisher,

B. Chen, X.-F. Wu / Journal of Catalysis 383 (2020) 160–163
163
183–186;
[10] (a) D.J. Wallace, D.J. Klauber, C.-Y. Chen, R.P. Volante, Org. Lett. 5 (24) (2003)
4749–4752;
f) Y. Li, H. Alper, Z. Yu, Org. Lett. 8 (2006) 5199–5201;
(g) R. Suleiman, J. Tijani, B.E.I. Ali, Appl. Organomet. Chem. 24 (2010) 38–46;
(h) Y. Uenoyama, T. Fukuyama, O. Nobuta, H. Matsubara, I. Ryu, Angew. Chem.,
Int. Ed. 44 (2005) 1075–1078;
(i) K.M. Driller, S. Prateeptongkum, R. Jackstell, M. Beller, Angew. Chem., Int.
Ed. 50 (2011) 537–541.
(b) M. Kiss, A. Takacs, L. Kollar, Current Green Chem. 2 (2015) 319–328;
(c) M. Gergely, L. Kollár, Tetrahedron 73 (2017) 838–844;
(d) R. Skoda-Foldes, L. Kollar, Lett. Org. Chem. 7 (2010) 621–633.
[11] (a) R.P. Bennett, W.B. Hardy, J. Am. Chem. Soc. 90 (1968) 3295–3296;
(b) L. Ren, N. Jiao, Chem. Commun. 50 (2014) 3706–3709;
(c) S.W. Yuan, H. Han, Y.L. Li, X. Wu, X. Bao, Z.Y. Gu, J.B. Xia, Angew. Chem. Int.
Ed. 58 (2019) 8887–8892.
[8] F. Sha, H. Alper, ACS Catal. 7 (2017) 2220–2229.
[9] J.-B. Peng, H.-Q. Geng, D. Li, X.-X. Qi, J. Ying, X.-F. Wu, Org. Lett. 20 (2018)
4988–4993.