CoBr2-TMTU-zinc catalysed-Pauson-Khand reaction

Article abstract of DOI:10.1039/c2cc17971g

A cobalt-TMTU complex, derived from the in situ reduction of CoBr ₂ with Zn in the presence of TMTU, can catalyze Pauson-Khand reaction at a balloon pressure of CO, which enables the synthesis of structurally diverse cyclopentenones. This catal

Full text of DOI:10.1039/c2cc17971g

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Dr Zhen Yang at Peking University, Beijing, China.
CoBr2–TMTU–zinc catalysed-Pauson–Khand reaction
A novel cobalt-TMTU complex, derived from the in situ
reduction of CoBr2 with Zn in the presence of TMTU can catalyze
the Pauson–Khand reaction under a balloon pressure of CO,
which enables the practical synthesis of cyclopentenones in terms
of potential flexibility and atom economy.
See Jiahua Chen, Zhen Yang et al.,
Chem. Commun., 2012, 48, 8183.
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COMMUNICATION
CoBr2–TMTU–zinc catalysed-Pauson–Khand reactionw
Yuefan Wang,a Lingmin Xu,a Ruocheng Yu,a Jiahua Chen*a and Zhen Yang*ab
Received 21st December 2011, Accepted 5th March 2012
DOI: 10.1039/c2cc17971g
A cobalt–TMTU complex, derived from the in situ reduction
of CoBr2 with Zn in the presence of TMTU, can catalyze
Pauson–Khand reaction at a balloon pressure of CO, which
enables the synthesis of structurally diverse cyclopentenones.
This catalytic system works efficiently for both intermolecular
and intramolecular PK reactions.
report our latest discovery of a practical and catalytic version
of the PK reaction by employing a novel type of Co-complex
system derived from the in situ reduction of CoBr2 with Zn in
the presence of tetramethyl thiourea (TMTU). Both CoBr2
and TMTU are commercially available and inexpensive, thus
making the reactions practically attractive.
We previously reported that substituted thioureas could
serve as effective ligands in the transition metal catalyzed
carbonylative reaction.9 We further identified that TMTU
was an effective ligand in Co2(CO)8- and PdCl2-catalyzed
PK reactions.10 Motivated by these encouraging findings, we
started to test the CoBr2-catalyzed PK reaction in the presence
of TMTU. After a number of experiments,11 we found out that a
Co-complex derived from the in situ reduction of CoBr2 (10 mol%)
with Zn (2 equiv.) in the presence of TMTU (60 mol%) could
perform as an efficient catalyst in the intermolecular PK
reactions. Resultantly, cyclopentenones 1c–8c were obtained
in good yields in the presence of molecular sieves12 at a balloon
pressure of CO at 70 1C (Table 1).
It is worthwhile to mention that TMTU plays a pivotal role in
this PK reaction, because when the same annulation reactions
were carried out with CoBr2–TMTU in a ratio less than 1/3, no
annulated products were obtained (see ESIw for details).
Considering the distinctive and beneficial role played by
TMTU in the Co-catalyzed PK reaction, we were motivated
to further test its beneficial effect on the intramolecular
Co-catalyzed PK reaction.13 To that end, 12 enynes (9a–20a)
were selected as substrates to undertake the annulation under
the optimized conditions. To our delight, the selected substrates
could give their corresponding products in good to excellent
yields (Table 2). It is worthwhile to mention that when
zinc amount was reduced to 0.2 mmol, the annulation of
substrate 10a could still proceed smoothly in the presence of
molecular sieves. However, upon further reduction of zinc
amount to less than 0.1 mmol, only a trace amount of
annulated product 10c was obtained (see ESIw for details).
We draw the following observations from the above results:
(1) both allylpropargyl malonates (entries 1–8) and allylpropargyl-
amines (entries 9–11) are good substrates and the expected
annulated product could be obtained in good to excellent
yields; (2) terminal alkynes as well as alkyl- or phenyl substituted
alkynes are good substrates that enable this PK reaction, which
is similar to the results generated in the rhodium-catalyzed PK
reaction,2q but in contrast to those observed in the titanium
catalyzed PK reaction.14 As a result, enynes, possessing both
electron donating and electron withdrawing groups, could give
The Pauson–Khand (PK) reaction,1 a cobalt-mediated coupling
of an alkene, an alkyne and CO that can produce a wide range
of substituted cyclopentenones, is one of the most powerful
reactions in organic synthesis (Scheme 1).
Scheme 1 The Pauson–Khand reaction.
In the past two decades, significant progress has been
witnessed in the transition metal-catalyzed PK reactions2
and the asymmetric PK reactions3 for the formation of a
variety of interesting cyclopentenones, which are not only
useful building blocks for more elaborate structures,4 but also
the core structures existing in numerous important biologically
active molecules.5
The Co-PK reaction has its downside though: it normally
adopts Co2(CO)8 as a stoichiometric reagent, which is toxic,
expensive as well as air and moisture sensitive; these factors
thus hinder the Co2(CO)8-based PK reaction from being applied
to large scale synthesis. In contrast with Co2(CO)8, CoBr2 is a
commercially available reagent with lower price, and is air and
moisture stable. The in situ reduction of a stoichiometric amount
of Co(II) with reducing agents (such as sodium-naphthalene and
NaH-sodium t-amyloxide) has been proven to generate an active
agent for the synthesis of cyclopentenones6 via inter- and intra-
molecular PK reaction.7 Yet, despite the efforts made in exploring
the CoBr2-mediated PK reaction by various improvements of
reaction conditions,8 a practical version of CoBr2-catalyzed
PK reaction has not been achieved. Herein, we would like to
a Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education and Beijing National Laboratory for
Molecular Science (BNLMS), College of Chemistry,
Peking University, Beijing, 100871, China. E-mail: zyang@pku.edu.cn
b Laboratory of Chemical Genomics, School of Chemical Biology and
Biotechnology, Peking University Shenzhen Graduate School,
Shenzhen, 518055, China
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c2cc17971g
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 8183–8185 8183

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Table 1 Intermolecular PK reactionsa
Table 2 Intramolecular PK reactions with allylpropargyl malonates
and allylpropargylaminesa
Time/ Yieldb
Entry Alkene Alkyne
Cyclopentenone
h
(%)
Time/ Yieldb
Entry
1
Enyne
Cyclopentenone
h
(%)
PhCRCH
1
2
3
4
5
6
7
24
85
1b
3
86
n-C5H11CRCH
24
15
15
11
24
93
86
75
88c
76
2b
2
3
3
3
91
90
pF–PhCRCH
3b
ptBu–PhCRCH
4b
4
5
94
pCN–PhCRCH
5b
5
6
7
3
3
5
88
93
83
PhCRCH
1b
n-C5H11CRCH
15
15
84
67
2b
pF–PhCRCH
8
3b
a
Reaction conditions: olefin (2.0 mmol), alkyne (1.0 mmol), CoBr2
(0.10 mmol), TMTU (6.60 mmol), Zn (2.0 mmol) and molecular sieves
8
9
16
3
72c
89
b
in toluene at 70 1C under CO (balloon pressure). Isolated yields.
c 1H NMR yield.
excellent yields of annulated products (entries 4–6); (3) different
from previous results,15 1,1-disubstituted olefins could also be
annulated to afford their corresponding products in good yields
(entries 2 and10).
10
11
3
73
The reaction mechanism is not yet clear and the detailed role
of TMTU in the reaction is to be determined in further studies.
Understanding the mechanistic aspect of this reaction and
applying this reaction to the total syntheses of natural products
are the subjects which we are currently investigating.
3
93
In summary, we have developed a practical and catalytic PK
reaction by employing CoBr2–TMTU–Zn as a novel catalyst,
which can accelerate the conversion of enynes into structurally
diverse cyclopentenones. As CoBr2–TMTU–Zn catalyzed PK
reaction has proven to be a practical and robust reaction,
thanks to the advantages of CoBr2 and TMTU including their
stability toward air and moisture, commercial availability and
affordable prices, our reported catalytic PK reaction should be
12
22
62c,d
a
Reaction conditions: enyne (0.5 mmol), CoBr2 (0.05 mmol), TMTU
(0.3 mmol), Zn (1.0 mmol) and molecular sieves in toluene at 70 1C
under CO (balloon pressure). Isolated yield. 20 mol% CoBr2 was
b
c
d
used. 90 1C.
c
8184 Chem. Commun., 2012, 48, 8183–8185
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useful in large scale synthesis of the cyclopentenones, and is
believed to contribute additional value to this powerful reaction.
This work was supported by the grants of National Basic
Research Program (973 Program, Grant 2012CB722602),
and the National Science Foundation of China (20821062,
20832003 and 20902007).
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11 See ESIw for details. The carbonylations were carried out by taking
precautions. The reaction and workup were carried out in a fume
hood.
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Chem. Commun., 2012, 48, 8183–8185 8185