Oxidative alkoxycarbonylation of terminal alkenes with carbazates

Article abstract of DOI:10.1039/c3cc42994f

A range of terminal alkenes smoothly underwent palladium-catalyzed oxidative alkoxycarbonylation with carbazates under an oxygen atmosphere to afford structurally diverse α,β-unsaturated esters in moderate to good yields with excellent regioselectivity and E selectivity.

Full text of DOI:10.1039/c3cc42994f

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Oxidative alkoxycarbonylation of terminal alkenes
with carbazates†
Yu-Han Su,a Zhao Wua and Shi-Kai Tian*ab
Cite this: Chem. Commun., 2013,
49, 6528
Received 23rd April 2013,
Accepted 14th May 2013
DOI: 10.1039/c3cc42994f
www.rsc.org/chemcomm
A range of terminal alkenes smoothly underwent palladium-catalyzed Prompted by our recent studies on the removal of the NHNH2
oxidative alkoxycarbonylation with carbazates under an oxygen atmo- group from sulfonyl hydrazides,8 together with our interest in
sphere to afford structurally diverse a,b-unsaturated esters in moderate alkene synthesis,9 we envisioned that treatment of simple
to good yields with excellent regioselectivity and E selectivity.
carbazates (ROCONHNH2) with palladium under oxidative
conditions could remove the NHNH2 group to generate certain
a,b-Unsaturated esters are present in many biologically relevant alkoxycarbonylpalladiums, which would couple with terminal
molecules, and moreover, they frequently serve as versatile synthetic alkenes to afford a,b-unsaturated esters.5b,6 Since simple carbazates
intermediates that are amenable to a range of transformations such are readily accessible solids, our proposed reaction was expected to
as addition, oxidation, and reduction.1 Thus, many efforts be much safer and more convenient to handle than that with CO.
have been devoted to the preparation of a,b-unsaturated esters,
To test our hypothesis, we employed 5 mol% Pd(OAc)2 to
for which convergent approaches commonly used include carbonyl catalyze the alkoxycarbonylation of styrene (1a) with ethyl
olefination and alkenylation.2 When compared with carbonyl carbazate (2a) in acetonitrile under an oxygen atmosphere at
olefination, alkenylation in general exhibits higher atom-economy 70 1C and found that a,b-unsaturated ester 3a was formed
in the synthesis of the same a,b-unsaturated esters. Particularly, albeit in a trace amount (Table 1, entry 1). To our delight, the
transformation of vinylic C–H bonds constitutes one of the most addition of CuCl to the reaction mixture led to the formation of
ideal methods to synthesize a,b-unsaturated esters. In this regard, a,b-unsaturated ester 3a in 31% yield with exclusive E selectivity
acrylates have been widely employed in the Mizoroki–Heck reaction (Table 1, entry 3). Molecular oxygen proved to be essential for
to couple with a variety of aryl sources such as aryl halides and the oxidative alkoxycarbonylation reaction judging by a control
sulfonates.3 Although the Mizoroki–Heck-type reaction has been experiment conducted under a nitrogen atmosphere, wherein
extended to aromatics via C–H functionalization under oxidative the desired product was not obtained at all (Table 1, entry 4).
conditions, it suffers from the use of excess starting materials, While no better yield was obtained by screening a number of
harsh conditions, and narrow substrate scope.4
solvents and copper sources (Table 1, entries 5–15), the addition of
In sharp contrast, little progress has been made in alter- 5 Å molecular sieves improved the yield to 62% (Table 1, entry 16).
native oxidative cross-coupling of ester groups with vinylic C–H It is noteworthy that the reaction failed to occur without a
bonds for the synthesis of a,b-unsaturated esters. Although palladium source (Table 1, entry 17), and replacing Pd(OAc)2 with
more than forty years ago CO and alcohols (solvents) were [Pd(allyl)Cl]2 gave a better yield (Table 1, entry 20). Whereas the
reported to serve as the sources of ester groups to couple with reaction did take place at a lower temperature, the desired product
terminal alkenes under oxidative conditions,5 little has been was obtained in a much lower yield (Table 1, entry 21). Finally, the
published on the refinement of such oxidative alkoxycarbonyla- yield was improved to 78% by increasing the amount of ethyl
tion reaction, which remains challenging in terms of harsh carbazate (2a) to 2 equivalents (Table 1, entry 22).
conditions, poor selectivity, and narrow substrate scope.6,7
In the presence of [Pd(allyl)Cl]2 (5 mol%), CuCl (2 equiv.),
and 5 Å molecular sieves, a range of arylethenes smoothly
underwent oxidative alkoxycarbonylation with ethyl carbazate
(2a) under an oxygen atmosphere to afford structurally diverse
a,b-unsaturated esters in moderate to good yields with excellent
regioselectivity and E selectivity (Table 2, entries 1–16). It is
noteworthy that both electron-withdrawing and electron-donating
groups were successfully introduced into the aromatic rings of the
products by employing the arylethenes bearing such groups, and
a Department of Chemistry, University of Science and Technology of China, Hefei,
Anhui 230026, China. E-mail: tiansk@ustc.edu.cn; Fax: +86 551-6360-1592;
Tel: +86 551-6360-0871
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
† Electronic supplementary information (ESI) available: Experimental proce-
dures, characterization data, and copies of 1H and 13C NMR spectra. See DOI:
10.1039/c3cc42994f
c
6528 Chem. Commun., 2013, 49, 6528--6530
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Table 1 Optimization of reaction conditionsa
(Table 2, entries 17 and 18), and consequently, the synthetic
utilities of this reaction could be significantly expanded in that
the benzyl and tert-butyl groups can be easily removed under
certain reaction conditions.10
The oxidative alkoxycarbonylation of alkylethenes and poly-
substituted alkenes was found to proceed sluggishly under the
standard reaction conditions. Moreover, carbon–carbon double
bond migration was observed in the reaction with 3-phenyl-1-
propene (1q), which afforded b,g-unsaturated ester 4 in 20%
yield (eqn. (1)). Such migration probably arises from selective
b-hydride elimination of the alkylpalladium intermediate generated
during the reaction (see below).
Entry
[Pd]
[Cu]
Solvent
Yieldb (%)
1
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
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
None
None
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl2
CuBr
CuI
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
MeCN
MeCN
MeCN
MeCN
PhMe
DCE
EtOAc
MeNO2
Dioxane
DMF
Trace
5
31
0
0
0
0
Trace
Trace
0
0
0
Trace
30
0
62
0
2c
3
4d
5
6
7
8
9
10
11
12
13
14
15
16e
17e
18e
19e
20e
21e,f
22e,g
DMSO
EtOH
(1)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
We did not observe any desired reaction between styrene (1a)
and ethyl 2-benzylhydrazinecarboxylate (5) under the standard
conditions (Fig. 1), and this result indicates that the NHNH2 group
is essential for the oxidative alkoxycarbonylation of terminal
alkenes with carbazates. In the reaction of styrene (1a) with ethyl
carbazate (2a), both alcohols 6 and ketones 7 were not detected by
1H NMR spectroscopic analysis of the crude products. Moreover,
treatment of ethyl carbazate (2a) with 2,2,6,6-tetramethyl-1-piper-
idine-1-oxyl (TEMPO) under the standard conditions did not result
in the formation of carbonate 8 (Fig. 1). These results are in sharp
contrast to Taniguchi and coworkers’ report on the generation of
methoxycarbonyl radicals from methyl carbazate in the presence of
iron phthalocyanine and air,11 and consequently, they suggested
that it is unlikely for alkoxycarbonyl radicals to serve as inter-
mediates in the oxidative alkoxycarbonylation of terminal alkenes
with carbazates.
PdCl2
27
Trace
70
35
78
Pd(PPh3)2Cl2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
a
Reaction conditions: alkene 1a (0.30 mmol), carbazate 2a (0.45 mmol),
[Pd] (5 mol%), [Cu] (0.60 mmol), O2 (1 atm), solvent (1.3 mL), 70 1C,
b
c
d
5 h. Isolated yield. 20 mol% CuCl was used. The reaction was run
e
under a nitrogen atmosphere. 5 Å molecular sieves (160 mg) were used.
f
g
The reaction was run at 50 1C. 0.60 mmol of carbazate 2a was used.
moreover, the reaction tolerated a variety of functional groups
such as fluoro, chloro, bromo, acetoxy, sulfonate, sulfone,
nitro, and nitrile. The chemistry was successfully extended to
the synthesis of benzyl and tert-butyl a,b-unsaturated esters
To gain more insights into the reaction mechanism, we carried
out electrospray ionization (ESI) mass spectrometric analysis of a
1 : 1 mixture of ethyl carbazate (2a) and [Pd(allyl)Cl]2 in acetonitrile.
Diazene 9a, carbazates 10a and 11a, and carbazate–Pd(II) com-
plexes 12a and 13a were tentatively assigned according to the high
resolution mass data (Fig. 1).12 These results suggest that diazenes
and Pd(0) are generated during the reaction through the inter-
mediacy of carbazate–Pd(II) complexes (see below).
On the basis of our experimental results, we propose the
following reaction pathways for the oxidative alkoxycarbonylation
of terminal alkenes with carbazates (Scheme 1). Displacement of
[Pd(allyl)Cl]2 with carbazate 2 results in the formation of carbazate–
Pd(II) complex 12, which undergoes reductive elimination to
Table 2 Oxidative alkoxycarbonylation of arylethenes with carbazatesa,b
Entry
1, R1
2, R2
3
Yieldc (%)
1
2
3
4
5
6
7
8
1a, Ph
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2a, Et
2b, CH2Ph
2c, CMe3
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
78
64
85
74
68
74
72
60
67
65
62
64
83
56
72
56
53
56
1b, 4-MeC6H4
1c, 4-AcOC6H4
1d, 4-TsOC6H4
1e, 4-FC6H4
1f 4-ClC6H4
1g, 4-BrC6H4
1h, 4-F3CC6H4
1i, 4-NCC6H4
1j, 4-MeS(O2)C6H4
1k, 4-O2NC6H4
1l, 3-O2NC6H4
1m, 2-ClC6H4
1n, 2-O2NC6H4
1o, 2-naphthyl
1p, 1-naphthyl
1a, Ph
9
10
11
12d
13
14
15
16d
17
18
1a, Ph
a
Reaction conditions: alkene 1 (0.30 mmol), carbazate 2 (0.60 mmol),
[Pd(allyl)Cl]2 (5 mol%), CuCl (0.60 mmol), 5 Å molecular sieves
b
(160 mg), O2 (1 atm), acetonitrile (1.3 mL), 70 1C, 5 h. Unless
otherwise stated, the product was obtained with >99 : 1 E/Z selectivity.
Isolated yield. 97 : 3 E/Z.
c
d
Fig. 1 Compounds 5–13a.
c
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2 For reviews, see: (a) S. E. Kelly, in Comprehensive Organic Synthesis,
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Scheme 1 Proposed reaction pathways.
give carbazate 10. Similar reaction of [Pd(allyl)Cl]2 with carbazate 10
gives carbazate 11. These displacement–elimination sequences allow
the generation of Pd(0), which is converted to PdCl2 through copper-
mediated oxidation.13–15 Displacement of PdCl2 with carbazate 2
followed by b-hydride elimination gives diazene 9 and releases
HPdCl. The attack of diazene 9 to PdCl2 followed by extrusion
of molecular nitrogen leads to the formation of alkoxycarbonyl-
palladium 17, which undergoes regioselective alkene insertion
followed by b-hydride elimination to give a,b-unsaturated ester 3
and release HPdCl.6 Reductive elimination of HPdCl regenerates
Pd(0) to continue the catalytic cycle.
In summary, we have developed an unprecedented oxidative
alkoxycarbonylation reaction of terminal alkenes with carbazates
for the synthesis of a,b-unsaturated esters in a highly regio- and
stereoselective manner. In the presence of [Pd(allyl)Cl]2 (5 mol%),
CuCl (2 equiv.), and 5 Å molecular sieves, a range of terminal
alkenes smoothly underwent oxidative alkoxycarbonylation with
carbazates under an oxygen atmosphere to afford structurally
diverse a,b-unsaturated esters in moderate to good yields with
excellent regioselectivity and E selectivity. The reaction tolerated a
variety of functional groups such as fluoro, chloro, bromo, acetoxy,
sulfonate, sulfone, nitro, and nitrile. Moreover, plausible reaction
pathways have been proposed for the palladium-catalyzed oxidative
alkoxycarbonylation of terminal alkenes with carbazates.
10 T. W. Greene and P. G. M. Wuts, Protective Groups in Organic
Synthesis, Wiley, New York, 3rd edn, 1999.
11 T. Taniguchi, Y. Sugiura, H. Zaimoku and H. Ishibashi, Angew.
Chem., Int. Ed., 2010, 49, 10154.
12 For details, see the ESI†.
13 A trace amount of the terminal alkene was consumed by the Wacker
oxidation, which was significantly suppressed by the addition of
molecular sieves. For reviews of the Wacker oxidation, see:
(a) J. M. Takacs and X. T. Jiang, Curr. Org. Chem., 2003, 7, 369;
(b) J. A. Keith and P. M. Henry, Angew. Chem., Int. Ed., 2009, 48, 9038.
14 In situ generation of PdCl2 is speculated to minimize aggregation
after being reduced to Pd(0). In contrast, direct use of PdCl2 gave a
much lower yield (Table 1, entry 18).
15 The reaction mixture turned pale green indicating the generation of
Cu(II) from Cu(I). Cu(II) was found to decompose carbazates,
and consequently, excess CuCl and carbazates were employed
for the oxidative alkoxycarbonylation of terminal alkenes. For
similar decomposition of acyl hydrazides with Cu(II), see: J. Tsuji,
T. Nagashima, N. T. Qui and H. Takayanagi, Tetrahedron, 1980,
36, 1311.
We are grateful for the financial support from the National
Natural Science Foundation of China (21232007 and 21172206),
the National Basic Research Program of China (973 Program
2010CB833300), and the Program for Changjiang Scholars and
Innovative Research Team in University (IRT1189).
Notes and references
1 F. A. Carey and R. J. Sundberg, Advanced Organic Chemistry Part B:
Reactions and Synthesis, Springer, New York, 5th edn, 2007.
c
6530 Chem. Commun., 2013, 49, 6528--6530
This journal is The Royal Society of Chemistry 2013