Palladium-catalyzed hydroaminocarbonylation of alkenes with amines: A strategy to overcome the basicity barrier imparted by aliphatic amines

Article abstract of DOI:10.1002/anie.201502405

A novel and efficient palladium-catalyzed hydroaminocarbonylation of alkenes with aminals has been developed under mild reaction conditions, and allows the synthesis of a wide range of N-alkyl linear amides in good yields with high regioselectivity. On the basis of this method, a cooperative catalytic system operating by the synergistic combination of palladium, paraformaldehyde, and acid was established for promoting the hydroaminocarbonylation of alkenes with both aromatic and aliphatic amines, which do not react well under conventional palladium-catalyzed hydroaminocarbonylation. Back to basics: The basicity of aliphatic amines precludes their use in the palladium-catalyzed hydroaminocarbonylation. This issue was overcome by using aminals as surrogates of aliphatic amines. A cooperative catalytic system was discovered to operate by the synergistic combination of palladium, paraformaldehyde, and acid for promotion of the hydroaminocarbonylation of alkenes with both aromatic and aliphatic amines.

Full text of DOI:10.1002/anie.201502405

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201502405
German Edition: DOI: 10.1002/ange.201502405
Synthetic Methods
Palladium-Catalyzed Hydroaminocarbonylation of Alkenes with
Amines: A Strategy to Overcome the Basicity Barrier Imparted by
Aliphatic Amines**
Guoying Zhang, Bao Gao, and Hanmin Huang*
Abstract: A novel and efficient palladium-catalyzed hydro-
aminocarbonylation of alkenes with aminals has been devel-
oped under mild reaction conditions, and allows the synthesis
of a wide range of N-alkyl linear amides in good yields with
high regioselectivity. On the basis of this method, a cooperative
catalytic system operating by the synergistic combination of
palladium, paraformaldehyde, and acid was established for
promoting the hydroaminocarbonylation of alkenes with both
aromatic and aliphatic amines, which do not react well under
conventional palladium-catalyzed hydroaminocarbonylation.
developed by the groups of Beller and Liu.[7] Although the
synthesis of a wide range of amides with high regioselectivity
and chemoselectivity is achievable, a high pressure of CO
(40 atm) is still required. The palladium hydride was consid-
ered to be a key reactive species in these processes, and is
preferentially trapped by alkenes to generate palladium alkyl
species, thus suppressing the formation of formamide by-
products. However, one common feature of these reactions is
the requisite use of aromatic amines as coupling partners
(Scheme 1a), which significantly limits the substrate scope of
A
mides are not only recognized as fundamental structural
motifs in myriad of natural products, pharmaceuticals, func-
tional materials, and agrochemicals,[1] but also serve as
attractive precursors in a variety of organic transformations.[2]
As such, the development of efficient methods toward amides
is of great significance to chemical, medicinal, and material
science and has attracted a great deal of attention over the
past decades.[3,4] In particular, the focal point is the creation of
catalytic protocols which possess the ability to transform
abundant, ideally renewable, feedstocks into amides in the
absence of stoichiometric by-products.[5–7] This goal can be
realized by alkene hydroaminocarbonylation with amines and
CO, and provides access to amides directly from alkenes
without formation of by-products. To date, however, only
a few catalytic systems dealing with hydroaminocarbonyla-
tion of alkenes have been reported.[6,7]
Early studies on hydroaminocarbonylation largely relied
on the use of Co, Ni, Fe, and Ru complexes as catalysts, which
not only suffered from requiring harsh reaction conditions
(> 70 atm CO, over 1508C) but also resulted in intricately
poor chemoselectivity.[6] This poor chemoselectivity stems
from the inherent preference for the generation of carbamoyl
metal complexes, which are prone to the formation of
significant amount of formamides as by-products. As
a means of addressing this problem, a mechanistically distinct
strategy with palladium complexes as catalysts has been
Scheme 1. Proposed palladium-catalyzed hydroaminocarbonylation of
alkenes with aminals.
the amines and reduces the appeal of these reactions. The
underlying reasons for the dependence of reactivity on the
nature of the amines might be attributed to the fact that the
key palladium hydride species only can be formed under
relatively acidic conditions.[8] Aliphatic amines which are
more basic (pKb < 5) may inhibit the generation of the key
palladium hydride species, thus preventing the N-alkyl-
substituted amides being formed. Thus, the development of
solutions to overcome the inherent side effect incurred by the
strong basicity of aliphatic amines would be highly desirable
to increase the range of amides which may be accessed.
[*] G. Zhang, B. Gao, Prof. Dr. H. Huang
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Lanzhou Institute of Chemical Physics
Chinese Academy of Sciences
Lanzhou, 730000 (China)
E-mail: hmhuang@licp.cas.cn
[**] This research was supported by the Chinese Academy of Sciences
and the National Natural Science Foundation of China (21222203,
21172226 and 21133011).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201502405.
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 1: Optimization of reaction conditions.[a]
Recently, we identified that aminals can react with
À
a copper complex to generate a copper amide species by C
N bond cleavage under mild reaction conditions.[9] This result
together with our progress on the use of aminals as electro-
philes for palladium-catalyzed coupling reactions[10]
prompted us to envision that aminals might be used as
surrogates of aliphatic amines to circumvent the inherent
substrate inhibition in the palladium-catalyzed hydroamino-
carbonylation reaction with aliphatic amines. Specifically, we
postulated that the palladium hydride species might be
generated in the presence of a catalytic amount of acid and
aminal since the basicity of the aminal is lower, and would
allow subsequent migratory insertion of the alkene and CO
into the palladium hydride species to generate the acyl
palladium species A. The interaction of A with an aminal
would allow generation of the key intermediate B together
Entry Ligand
Acid
3aa+4aa [%][b] 3aa/4aa[c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
DPPF
DPPM
DPPE
DPPP
DPPB
NH2CH2CO2Me·HCl
NH2CH2CO2Me·HCl
NH2CH2CO2Me·HCl
NH2CH2CO2Me·HCl
NH2CH2CO2Me·HCl
13
trace
0
80:20
–
–
–
–
83:17
61:39
–
–
–
0
trace
87
57
trace
trace
trace
trace
47
63
69
82
69
DPPPen NH2CH2CO2Me·HCl
DPPH NH2CH2CO2Me·HCl
Xantphos NH2CH2CO2Me·HCl
DPEphos NH2CH2CO2Me·HCl
DPPPen TsOH
DPPPen NH2CH2CO2H
DPPPen NH2OH·HCl
DPPPen NEt3·HCl
À
with the iminium C through C N bond cleavage. The iminium
C would quickly react with another molecule of A, facilitated
by water, to afford the second molecule of B together with
paraformaldehyde and acid (HX). Reductive elimination of B
leads to the final hydroaminocarbonylation products (Sche-
me 1b). On the basis of this mechanistic assumption, we
recognized that cooperative catalysis consisting of palladium,
paraformaldehyde, and acid might be also feasible to promote
the hydroaminocarbonylation with simple amines as coupling
partners, and the paraformaldehyde and acid cocatalyst may
act as temporary masking groups to eliminate the side effect
resulting from the basicity of aliphatic amines. Herein, we
describe a new and efficient protocol for the successful
implementation of the palladium-catalyzed hydroaminocar-
–
82:18
81:19
84:16
82:18
83:17
DPPPen NH2CH2CO2H·HCl
DPPPen NH2CH2CO2Et·HCl
DPPPen NH2CH(Ph)CO2Me·HCl
[a] General conditions: 1a (0.8 mmol), 2a (0.2 mmol), Pd(TFA)2
(0.01 mmol), ligand (0.012 mmol), acid (0.04 mmol), H2O (0.22 mmol),
anisole (1.0 mL), and CO (10 atm), at 1208C for 21 h. [b] Yields were
determined by GC analysis using n-cetane as the internal standard.
[c] The ratios of 3aa/4aa (linear/branched; l/b) were determined by GC
analysis. TFA=trifluoroacetate, Ts=4-toluenesulfonyl.
À
bonylation of alkenes with a variety of aminals by C N bond
cleavage, and it allows synthesis of a variety of N-alkyl-
substituted amides under mild reaction conditions. Further-
more, a cooperative catalytic system combined with palla-
dium, paraformaldehyde, and acid was also established for
promoting the hydroaminocarbonylation of alkenes with both
aliphatic and aromatic amines.
amino hydrochlorides. As anticipated, control reactions
demonstrated that only trace amounts of the amide product
were obtained in the absence of acid. In addition, we
examined the effect of the palladium source and observed
that other palladium precursors provided unsatisfactory
results in terms of reactivity and selectivity (see the Support-
ing Information).
To validate our hypothesis, the hydroaminocarbonylation
reaction was initially investigated with styrene (1a) and the
aminal 2a in the presence of a catalytic amount of Pd(TFA)2,
acid, and H2O (0.55 equiv) under 10 atm of CO in anisole at
1208C (Table 1). Low yield of the hydroaminocarbonylation
product was obtained with most of the styrene remaining
when DPPF served as a ligand (entry 1). The probable reason
for the lower conversion could be attributed to the nature of
the palladium catalyst. Evaluation of various phosphine
ligands revealed that the transformation was sensitive to the
bite angle of the bisphosphine ligand and found that DPPPen,
which possesses a larger bite angle, afforded the product in
good yield (87% yield) and high regioselectivity (entry 6). It
should be noted that the two amino moieties of the aminal
were successfully incorporated into the desired amide, thus
suggesting that our strategy is feasible. The structure of the
main product 3aa was confirmed by X-ray single-crystal
diffraction analysis.[11] Furthermore, the impact of acid on the
reactivity and regioselectivity of the process was investigated
(entries 10–16). NH2CH2CO2Me·HCl emerged as the acid of
choice to give the desired product in 87% yield, while
a comparable result was obtained in the presence of other
Our hypothesis was amenable to a wide range of alkene
substrates, thus allowing preparation of one-carbon elongated
amides from olefins in high yields and good to excellent
selectivities (Table 2). It was even more intriguing that
generally no formamide byproduct was observed, and in
most cases, more than 70% yield was isolated for linear
adducts. Both electron-rich and electron-deficient aromatic
alkenes could be employed efficiently in our protocol (3ba–
ka). For styrenes, a series of functional groups, such as methyl,
methoxy, fluoro, and chloro contained in the phenyl ring were
compatible with the present catalytic system, and the desired
products were isolated in good to excellent yields, which
indicated that the present reaction had a good functional-
group tolerance. Preference for the formation of linear
adducts soared upon increase of steric demand in the
substrates as exemplified by ortho-substituted styrenes (3da,
3ea, 3ja, 3ka). 4-Vinylpyridine underwent the desired
reaction to give the branched product in a relatively lower
2
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Table 2: Substrate scope of alkenes.[a]
strated by reactions of 4-vinylcyclohex-1-ene and (+)-b-
citronellene, in which the reactions took place exclusively at
the terminal double bond to give the corresponding linear
amides 6ba (80%) and 6ca (92%), respectively, while the
internal double bond remained intact. To further demonstrate
the robustness of our system, we were able to run experiments
on gram scale in the presence of 1 mol% of the palladium
catalyst to produce the linear amide 3qa in 83% yield (3.49 g;
entry 17).
Entry
R
Product
Yield [%][b]
l/b[c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
C6H5
3aa
3ba
3ca
3da
3ea
3 fa
3ga
3ha
3ia
72
73
80
90
90
69
42
62
83:17
81:19
87:13
95:5
95:5
82:18
83:17
88:12
88:12
94:6
94:6
1:99
4-CH3C6H4
3-CH3C6H4
2-CH3C6H4
2,6-(CH3)2C6H3
4-tBuC6H4
4-CH3OC6H4
4-FC6H4
Having demonstrated that the process is compatible with
a wide range of alkenes, investigation of the scope with
respect to the aminal was undertaken (Table 3). Several
Table 3: Substrate scope of aminals.[a]
4-ClC6H4
70
62
68
2,6-Cl2C6H3
2,3-Cl2C6H3
4-pyridinyl
H
CH3(CH2)5
CH3(CH2)7
CH3(CH2)9
CH3(CH2)11
CH3(CH2)13
CH3(CH2)15
C6H5CH2
3ja
3ka
4la
34
3ma
3na
3oa
3pa
3qa
3ra
3sa
3ta
3ua
3va
3wa
3xa
3ya
3za
6aa
89[d]
80
–
96:4
95:5
90:10
94:6
94:6
93:7
93:7
93:7
95:5
92:8
91:9
82
85
84 (83)[e]
80
82
85
82
86
83
79
88
73
4-CH3OC6H4CH2
C6H5(CH2)2
CyCH2
Cl(CH2)4
[a] General conditions: 1q (0.8 mmol), 2 (0.2 mmol), CO (10 atm),
Pd(TFA)2 (0.01 mmol), DPPPen (0.012 mmol), NH2CH2CO2Me·HCl
(0.04 mmol), and H2O (0.22 mmol) in anisole (1.0 mL) at 1208C for
21 h. Yield of isolated linear product based on amino moiety; the l/b
ratios within parentheses were determined by GC and GC-MS analysis.
[b] Acid (0.2 mmol).
CH3CO(CH2)2
EtOOC(CH2)2
CH3COO(CH2)4
92:8
86:14
90:10
73
aminals (2b–e) derived from diethylamine, dipropylamine,
dibutylamine, and morpholine were effective substrates for
reacting with tetradec-1-ene smoothly to provide the products
3qb–qe in 70–89% yields with high regioselectivity. However,
the aminal 2 f derived from piperidine was less reactive, and
the linear adduct 3qf was obtained in only 55% yield upon
isolation.
[a] General conditions: 1 (0.8 mmol), 2a (0.2 mmol), CO (10 atm),
Pd(TFA)2 (0.01 mmol), DPPPen (0.012 mmol), NH2CH2CO2Me·HCl
(0.04 mmol), and H2O (0.22 mmol) in anisole (1.0 mL) at 1208C for
21 h. [b] Yield of isolated linear product based on amino moiety. [c] The l/
b ratios were determined by GC and GC-MS analysis. [d] Ethene (5 atm).
[e] Gram scale.
As the proposed design was partially realized by success-
fully employing aminals as aliphatic amine sources for the
hydroaminocarbonylation of alkenes, we wanted to further
investigate whether cooperative catalysis by the combination
of palladium, paraformaldehyde, and acid could promote the
desired carbonylation with free primary or secondary amines
as coupling partners. To our delight, the combination of
2.5 mol% of Pd(TFA)2, 3 mol% of DPPPen, 10 mol% of
acid, and 10 mol% of paraformaldehyde was identified as an
efficient cooperative catalytic system for promoting the
desired hydroaminocarbonylation. Control reactions demon-
strated that only trace amounts of the amide product were
obtained in the absence of paraformaldehyde. By using the
procedure in Table 4, the hydroaminocarbonylation of tetra-
dec-1-ene with aliphatic and aromatic amines, such as
dibenzylamine, morpholine, benzylamine, butylamine, and
aniline, proceeded smoothly to generate the desired linear
amides in moderate to excellent yields (3qa–qi). Similar
yield with complete regioselectivity under the current reac-
tion conditions. Next, we turned our attention to more
challenging aliphatic alkenes. Ethene was initially surveyed
and the reaction proceeded smoothly to give the desired
amide 3ma in 89% yield with 5 atm of ethene and 10 atm of
CO. Furthermore, similar results were obtained in the
reactions of terminal aliphatic alkenes with long chains to
deliver the linear amides efficiently in 80–86% yields with
high regioselectivities (3na–sa). Allylbenzene and 3-butenyl-
benzene were compatible for the reaction conditions, thus
affording the corresponding products in excellent yields with
high regioselectivities (3ta–3va). Typical functional groups on
the aliphatic alkenes, such as cyclohexyl, chloro, ketone, and
ester, were also well tolerated by the reaction conditions,
thereby affording the corresponding linear adducts in 73–
88% yields with high regioselectivities (entries 23–27). The
reaction was not applicable to internal alkenes, as demon-
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
Table 4: Hydroaminocarbonylation with aliphatic and aromatic amines
Keywords: alkenes · amines · aminals · palladium ·
synthetic methods
by a cooperative catalysis with paraformaldehyde.[a]
[1] a) J. W. Clader, J. Med. Chem. 2004, 47, 1; b) J. W. Bode, Curr.
Opin. Drug Discovery. Dev. 2006, 9, 765; c) W. Wu, Z. Zhang,
L. S. Liebeskind, J. Am. Chem. Soc. 2011, 133, 14256; d) S.
Eichner, T. Eichner, H. G. Floss, J. Fohrer, E. Hofer, F. Sasse, C.
Zeilinger, A. Kirschning, J. Am. Chem. Soc. 2012, 134, 1673;
e) X. Wang, F. Meng, Y. Wang, Z. Han, Y.-J. Chen, L. Liu, Z.
Wang, K. Ding, Angew. Chem. Int. Ed. 2012, 51, 9276; Angew.
˝
Chem. 2011, 123, 9410; f) H. Noda, G. Eros, J. W. Bode, J. Am.
Chem. Soc. 2014, 136, 5611.
[2] a) L. Crespo, G. Sanclimens, M. Pons, E. Giralt, M. Royo, F.
Albericio, Chem. Rev. 2005, 105, 1663; b) M. A. Mintzer, E. E.
Simanek, Chem. Rev. 2009, 109, 259; c) U. Boas, J. Brask, K. J.
Jensen, Chem. Rev. 2009, 109, 2092; d) D. W. Zhang, X. Zhao,
J. L. Hou, Z. T. Li, Chem. Rev. 2012, 112, 5271; e) E. B. Divito,
M. Cascio, Chem. Rev. 2013, 113, 7343; f) X. Guo, A. Facchetti,
T. J. Marks, Chem. Rev. 2014, 114, 8943; g) D.-W. Zhang, X.
Zhao, Z.-T. Li, Acc. Chem. Res. 2014, 47, 1961.
[3] For reviews, see: a) J. M. Humphrey, A. R. Chamberlin, Chem.
Rev. 1997, 97, 2243; b) G. Kiss, Chem. Rev. 2001, 101, 3435; c) S.-
Y. Han, Y.-A. Kim, Tetrahedron 2004, 60, 2447; d) F. Albericio,
Curr. Opin. Chem. Biol. 2004, 8, 211; e) C. A. G. N. Montalbetti,
V. Falque, Tetrahedron 2005, 61, 10827; f) E. Valeur, M. Bradley,
Chem. Soc. Rev. 2009, 38, 606; g) A. Brennfꢀhrer, H. Neumann,
M. Beller, Angew. Chem. Int. Ed. 2009, 48, 4114; Angew. Chem.
2009, 121, 4176; h) V. R. Pattabiraman, J. W. Bode, Nature 2011,
480, 471; i) C. L. Allen, J. M. J. Williams, Chem. Soc. Rev. 2011,
40, 3405; j) X.-F. Wu, H. Neumann, M. Beller, Chem. Soc. Rev.
2011, 40, 4986; k) Q. Liu, H. Zhang, A. Lei, Angew. Chem. Int.
Ed. 2011, 50, 10788; Angew. Chem. 2011, 123, 10978; l) X.-F. Wu,
H. Neumann, M. Beller, Chem. Rev. 2013, 113, 1; m) X.-F. Wu,
X. Fang, L. Wu, R. Jackstell, H. Neumann, M. Beller, Acc. Chem.
Res. 2014, 47, 1041.
[4] For selected examples of amides from carboxylic acids or esters,
see: a) C. Han, J. P. Lee, E. Lobkovsky, J. A. Porco, J. Am. Chem.
Soc. 2005, 127, 10039; b) M. Hosseini-Sarvari, H. Sharghi, J. Org.
Chem. 2006, 71, 6652; Amides from aldehydes or alcohols: c) C.
Gunanathan, Y. Ben-David, D. Milstein, Science 2007, 317, 790;
d) L. U. Nordstrøm, H. Vogt, R. Madsen, J. Am. Chem. Soc.
2008, 130, 17672; e) T. Zweifel, J.-V. Naubron, H. Grꢀtzmacher,
Angew. Chem. Int. Ed. 2009, 48, 559; Angew. Chem. 2009, 121,
567; f) M. W. Leighty, B. Shen, J. N. Johnston, J. Am. Chem. Soc.
2012, 134, 15233; g) B. Kang, Z. Fu, S. H. Hong, J. Am. Chem.
Soc. 2013, 135, 11704; h) J. Dong, E. C. Harvey, M. FaÇanꢁs-
Mastral, W. R. Browne, B. L. Feringa, J. Am. Chem. Soc. 2014,
136, 17302; For selected examples of aminocarbonylation, see:
i) P. Hermange, A. T. Lindhardt, R. H. Tanning, K. Bjerglund, D.
Lupp, T. Skrydstrup, J. Am. Chem. Soc. 2011, 133, 6061; j) X.-F.
Wu, H. Neumann, M. Beller, Chem. Eur. J. 2012, 18, 419;
k) M. V. Khedkar, T. Sasaki, B. M. Bhanage, ACS Catal. 2013, 3,
287; l) W. Li, C. Liu, H. Zhang, K. Ye, G. Zhang, W. Zhang, Z.
Duan, S. You, A. Lei, Angew. Chem. Int. Ed. 2014, 53, 2443;
Angew. Chem. 2014, 126, 2475.
[a] General conditions: 1 (0.8 mmol), 5 (0.4 mmol), CO (10 atm),
Pd(TFA)2 (0.01 mmol), DPPPen (0.012 mmol), NH2CH2CO2Me·HCl
(0.04 mmol), and (HCHO)n (0.04 mmol) in anisole (1.0 mL) at 1208C for
21 h. Yield of isolated linear product based on amino moiety; the l/b
ratios shown within parentheses were determined by GC and GC-MS
analysis. [b] Gram scale. [c] Acid (0.2 mmol), CO (40 atm). [d] No
(HCHO)n.
results were obtained in the reactions of other aliphatic
alkenes and styrene to give rise to a variety of linear amides in
good yields with high regioselectivity under the current
reaction conditions (3ag–xg). Notably, the aniline 5i can be
applied to this process in the absence of paraformaldehyde,
thus giving the desired products 3qi and 3di in good yields.
The structure of 3ag was confirmed by X-ray single-crystal
diffraction analysis.[11] The gram-scale reaction was success-
fully realized with 1 mol% of the palladium catalyst in the
presence of 10 mol% (HCHO)n and a catalytic amount of
acid, thus affording 3qa in 72% (3.03 g) yield (see the
Supporting Information).
In summary, we have developed a new and efficient
protocol for implementation of the palladium-catalyzed
hydroaminocarbonylation of simple alkenes with a variety
of aminals, which successfully overcomes the difficulty of
using aliphatic amines and allows synthesis of a broad range
of N-alkyl-substituted amides under mild reaction conditions.
On the basis of this method, a cooperative catalytic system
through the synergistic combination of palladium, para-
formaldehyde, and acid was also established for promoting
the hydroaminocarbonylation of alkenes with both aliphatic
and aromatic amines. This study not only provides an efficient
method to realize the hydroaminocarbonylation with both
aliphatic and aromatic amines under mild reaction conditions,
[5] a) S.-I. Murahashi, Y. Imada, K. Nishimura, J. Chem. Soc. Chem.
Commun. 1988, 1578; b) S.-I. Murahashi, Y. Imada, K. Nishi-
mura, Tetrahedron 1994, 50, 453; c) H. Yu, G. Zhang, Z.-J. Liu,
H. Huang, RSC Adv. 2014, 4, 64235.
[6] a) P. Pino, P. Paleari, Gazz. Chim. Ital. 1951, 81, 64; b) W. Reppe,
H. Kroper, Ger. Pat. 1951, 149, 868; c) P. Pino, R. Magri, Chim.
Ind. 1952, 34, 511; d) G. Natta, P. Pino, R. Ercoli, J. Am. Chem.
Soc. 1952, 74, 4496; e) W. Reppe, H. Main, Chem. Abstr. 1953,
47, 5428; f) B. F. Crowe, O. C. Elmer, Chem. Abstr. 1956, 50,
À
but also paves the way for establishing new C N bond-
formation reactions by using this cooperative catalysis.
Studies aimed at gaining a detailed mechanistic understand-
ing of this reaction and the application of this strategy in other
reactions are currently in progress.
4
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
16849; g) T. J. Kealy, R. E. Benson, J. Org. Chem. 1961, 26, 3126;
h) A. Striegler, J. Weber, J. Prakt. Chem. 1965, 29, 281; i) N. S.
Imyanitov, D. M. Rudkvsku, Chem. Abstr. 1967, 66, 10530;
j) B. K. Nefedov, N. S. Sergeeva, Y. T. Eidus, Chem. Abstr. 1975,
83, 205731; k) Y. Tsuji, T. Ohsumi, T. Kondo, Y. Watanabe, J.
Organomet. Chem. 1986, 309, 333; l) S. I. Lee, S. U. Son, Y. K.
Chung, Chem. Commun. 2002, 1310.
[9] a) Y. Xie, B. Qian, P. Xie, H. Huang, Adv. Synth. Catal. 2013, 355,
1315; b) Y. Zhou, H. Huang, Tetrahedron Lett. 2013, 54, 2713.
[10] a) Y. Xie, J. Hu, Y. Wang, C. Xia, H. Huang, J. Am. Chem. Soc.
2012, 134, 20613; b) Y. Xie, J. Hu, P. Xie, B. Qian, H. Huang, J.
Am. Chem. Soc. 2013, 135, 18327; c) J. Hu, Y. Xie, H. Huang,
Angew. Chem. Int. Ed. 2014, 53, 7272; Angew. Chem. 2014, 126,
7400.
[7] a) X. Fang, R. Jackstell, M. Beller, Angew. Chem. Int. Ed. 2013,
52, 14089; Angew. Chem. 2013, 125, 14339; b) H. Liu, N. Yan, P. J.
Dyson, Chem. Commun. 2014, 50, 7848; c) X. Fang, H. Li, R.
Jackstell, M. Beller, J. Am. Chem. Soc. 2014, 136, 16039; d) J.
Cheng, X. Qi, M. Li, P. Chen, G. Liu, J. Am. Chem. Soc. 2015,
137, 2480.
[11] CCDC 1048178 (3aa) and 1048179 (3ag) contain the supple-
mentary crystallographic data for this paper. This data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[8] a) B. M. Trost, W. Pfrengle, H. Urabe, J. Dumas, Acc. Chem. Res.
1990, 23, 34; b) V. V. Grushin, Chem. Rev. 1996, 96, 2011;
c) B. M. Trost, Chem. Eur. J. 1998, 4, 2405; d) F. Alonso, I. P.
Beletskaya, M. Yus, Chem. Rev. 2004, 104, 3079.
Received: March 14, 2015
Revised: April 20, 2015
Published online: && &&, &&&&
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Synthetic Methods
G. Zhang, B. Gao,
H. Huang*
&&&& — &&&&
Palladium-Catalyzed
Hydroaminocarbonylation of Alkenes
with Amines: A Strategy to Overcome the
Basicity Barrier Imparted by Aliphatic
Amines
Back to basics: The basicity of aliphatic
amines precludes their use in the palla-
dium-catalyzed hydroaminocarbonyla-
tion. This issue was overcome by using
aminals as surrogates of aliphatic
was discovered to operate by the syner-
gistic combination of palladium, para-
formaldehyde, and acid for promotion of
the hydroaminocarbonylation of alkenes
with both aromatic and aliphatic amines.
amines. A cooperative catalytic system
6
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!