Cobalt-catalyzed cyclization of carbon monoxide, imine, and epoxide

Article abstract of DOI:10.1021/ol500549c

Cobalt-catalyzed cyclization of CO, imine, and epoxide has been developed. A convenient catalyst system composed of Co₂(CO)₈ and LiCl is identified, and the substrate scope has been explored. The reaction provides an efficient method for the synthesis of substituted 1,3-oxazinan-4-ones.

Full text of DOI:10.1021/ol500549c

Letter
pubs.acs.org/OrgLett
Cobalt-Catalyzed Cyclization of Carbon Monoxide, Imine, and
Epoxide
Yubo Zhang,† Jiamin Ji,† Xiuliang Zhang,† Shaohui Lin,*,† Qinmin Pan,*,† and Li Jia*,‡
†Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Key Laboratory of Organic Synthesis of Jiangsu
Province, Green Polymer and Catalysis Technology Laboratory (GAPCT), College of Chemistry, Chemical Engineering and
Materials Science, Soochow University, Suzhou 215123, P. R. China
‡Department of Polymer Science, University of Akron, 170 University Avenue, Akron, Ohio 44325, United States
S
* Supporting Information
ABSTRACT: Cobalt-catalyzed cyclization of CO, imine, and epoxide has been
developed. A convenient catalyst system composed of Co2(CO)8 and LiCl is
identified, and the substrate scope has been explored. The reaction provides an
efficient method for the synthesis of substituted 1,3-oxazinan-4-ones.
etal-catalyzed carbonylation is a powerful method for
the construction of amide and ester bonds.1,2 In the past
ratio of trans-3aa/cis-3aa was approximately 1:3. No
regioisomer was observed due to the ring opening at the
more hindered carbon of propylene oxide.
M
decade, mechanism-based development of well-defined cobalt
catalysts resulted in the vast improvement of the efficiency,
selectivity, and scope of this type of catalytic reaction. The
utility of this type of reaction has been expanded from the
synthesis of organic compounds3−5 to polymer synthesis.6−9
As part of our continuous effort in the area of carbonylative
polymerization of heterocycles, we probed the possibility of
effecting a triply alternating copolymerization of CO, N-
benzylidenemethylamine, and propylene oxide using
CH3COCo(CO)3P(o-Toly)3 (A) as the catalyst (Scheme 1).
Instead of the anticipated polymer, the reaction afforded a
cyclization product,10 which was readily diagnosed with mass
spectrometry.
1,3-Oxazinan-4-ones are useful intermediates for many
important pharmaceutical compounds.11a They are typically
synthesized by hetero-Diels−Alder reactions involving multi-
step substrate preparation.11 The present novel catalytic
reaction potentially provides a new and convenient route to
the preparation of 1,3-oxazinan-4-ones from very simple and
often commercially available starting materials. We therefore
followed up on this accidental discovery and report here our
preliminary results on catalyst optimization and substrate
scouting. Parenthetically, it should be noted that the present
accidentally discovered reaction bears a direct analogy to the
synthesis of 1,3-oxazinane-2,4-diones from epoxides, isocya-
nates, and CO developed by Coates and co-workers.12
Following the initial discovery, we first attempted to improve
the yield of the reaction. With A as the catalyst, the best yield
was obtained at 70 °C in dioxane (Table 1, entry 3). The yield
was lower at higher or lower temperatures (Table 1, entries 2
and 4) and when other solvents were used (Table 1, entries 5
and 6). The reaction conversion of the starting materials was
incomplete in all these cases at 5 mol % catalyst loading.
Catalysts CH3COCo(CO)3PPh3 (B) and PhCH2COCo(CO)4
(C) also resulted in low yields (entries 7 and 8). The yield is
unsatisfactory even under optimized conditions. A more
efficient catalyst is necessary for the reaction to be synthetically
useful.
Scheme 1. Initial Investigation of Cobalt-Catalyzed
Carbonylation Involving Imine and Epoxide
Further inspection of the product indicated that it contained
a pair of isomers, which were separated by column
chromatography. One- and two-dimensional NMR spectro-
While it is required for carbonylative polymerization, the acyl
group in A−C may encumber the intramolecular cyclization.13
We thus moved away from the acyl-cobalt compounds and
tested Co2(CO)8/3-hydroxypyridine as the catalyst (Table 1,
entries 9, 10).3k The cyclization indeed occurred to afford trans-
and cis-3aa in 92% yield. A very small amount of polyester was
1
1
scopic data including H, 13C, DEPT, H−1H COSY, and
1H−1H NOESY spectra confirmed that they were trans- and cis-
3,6-dimethyl-2-phenyl-1,3-oxazinan-4-one (trans-3aa and cis-
3aa). The individual diastereomeric configuration was assigned
1
according to the H−1H NOESY spectra of the two isomers.
Correlation of the protons at the C2 and C6 positions was
Received: February 20, 2014
Published: March 28, 2014
observed in the cis-isomer and absent in the trans-isomer. The
© 2014 American Chemical Society
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Organic Letters
Letter
Table 1. Cobalt-Catalyzed Cyclization of N-
Benzylidenemethylamine, Propylene Oxide, and CO
Table 2. Scope of Substrates for Cyclization of Imine,
a
a
Epoxide, and CO Catalyzed by Co2(CO)8/LiCl
temp
(°C)
yield
b
entry
catalyst
solvent
(%)
c
1
A
A
A
A
A
A
B
C
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
THF
50
60
70
80
70
70
70
70
70
60
70
24
c
2
43
c
3
59
c
4
23
c
5
35
6
toluene
trace
c
7
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
17
c
8
20
cd
,
9
Co2(CO)8/3-hydroxypyridine
Co2(CO)8/3-hydroxypyridine
92
80
91
cd
,
10
11
cd
,
Co2(CO)8/3-hydroxypyridine/
f
LiCl
e
c
c
c
c
c
12
13
14
15
16
17
18
Co2(CO)8/LiCl
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
70
70
70
60
70
70
70
40
95
90
89
41
f
Co2(CO)8/LiCl
g
Co2(CO)8/LiCl
f
Co2(CO)8/LiCl
f
NaCo(CO)4/LiCl
NaCo(CO)4
Co2(CO)8
trace
trace
a
Reaction conditions: imine (3.00 mmol), epoxide (4.50 mmol),
catalyst (0.15 mmol, 5 mol %), solvent (50 mL), 800 psi CO, 24 h.
b
c
Isolated yield. Diastereomer ratios were determined by HPLC, and
d
all the trans/cis ratios were approximately 1:3. Polyester observed.
e
f
g
LiCl/Co2(CO)8 = 1.0. LiCl/Co2(CO)8 = 2.0. LiCl/Co2(CO)8 =
3.0.
also observed in the crude product. Since lithium salts often can
modulate the rate and selectivity of the ring opening of
heterocyclic molecules, 2 equiv of LiCl relative to Co2(CO)8
(i.e., the mole ratio of LiCl/Co2(CO)8 = 1:1) were added into
the reaction. The outcome of the reaction was not affected to
any substantial extent (Table 1, entry 11). However, a
subsequent control experiment catalyzed by Co2(CO)8/LiCl
demonstrated that 3-hydroxypyridine was unnecessary (Table
1, entries 9−13). On the other hand, Co2(CO)8 alone gave
only a trace amount of the anticipated product in the absence of
LiCl with the starting materials mostly remaining unreacted
(Table 1, entry 18). When only 1 equiv of LiCl was used, the
yield was 40% (Table 1, entry 12). When 3 equiv of LiCl were
used (Table 1, entry 14), the yield was again somewhat lower
than that when 2 equiv of LiCl were used. It appears that the
optimal amount of LiCl is 2 equiv (Table 1, entries 12−14).
NaCo(CO)4 also gave a modest yield of the anticipated
product in the presence of 2 equiv of LiCl (Table 1, entry 16).
Again, only trace product was observed in the absence of LiCl
with NaCo(CO)4 as the catalyst (Table 1, entry 17). The same
approximately 1:3 diastereomeric ratio was observed in all runs
discussed above.
a
Reaction conditions: imine (3.00 mmol), epoxide (4.50 mmol),
Co2(CO)8 (0.15 mmol, 5 mol %), LiCl (0.30 mmol), 1,4-dioxane (50
b
c
mL), 800 psi CO, 70 °C, 24 h. Isolated yield. Diastereomer cis/trans
ratios determined by HPLC. Detected by LC-Mass.
d
again selectively at the less hindered carbon. When styrene
oxide and cyclohexene oxide were used as the substrate, the
expected cyclization did not occur,12 and the substrates were
recovered. The para-substituent on the N-benzylidenemethyl-
amine affected the diastereoselectivity of the reaction somewhat
with propylene oxide serving as the epoxide substrate, but the
cis-isomer was always the major isomer (entries 1, 5, 6). An
increase in the electron-withdrawing ability of the aryl group in
the imine substrate increases the yield of the reaction (entries
7−10). In the case of N-(para-bromo-benzylidene)methyl-
amine (entry 11), the low yield is likely attributable to the
participation of the para-bromo group in the reaction. Finally,
After identification of the Co2(CO)8/LiCl system as an
efficient catalyst, the scope of the substrate for the reaction was
explored. With N-benzylidenemethylamine serving as the
invariant substrate, a few representative epoxides were tested
(Table 2, entries 1−4). The reaction of isobutylene oxide
afforded the anticipated product in decent but lower yield than
that of the reaction of propylene oxide. Ring opening occurred
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Organic Letters
Letter
Scheme 2. Two Plausible Mechanisms for the Cobalt-Catalyzed Cyclization of Imine, Epoxide, and CO
an aryl substituent on the imine substrate is required. For tert-
butylidenemethylamine, only a trace amount of expected
product was detected by LC-Mass spectrometry.
*E-mail: ljia@uakron.edu.
Notes
In regard to the mechanism of the reaction,3e,4a,7d,14 [Lewis
acid]+[Co(CO)4]− is likely the active species although the
identity of the Lewis acid (LA) may vary with the specific
catalyst system that is used. Two plausible catalytic cycles can
be envisioned that differ in the order in which the imine and
epoxide react as shown in Scheme 2. In catalytic cycle I, upon
epoxide coordination to the Lewis acid, nucleophilic addition of
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This paper is dedicated to Professor Xiyan Lu (Shanghai
Institute of Organic Chemistry, CAS, China) on the occasion of
his 85th birthday. We gratefully acknowledge the National
Natural Science Foundation of China (No. 21104049),
Specialized Research Fund for the Doctoral Program
(SRFDP) of Higher Education (No. 20113201120006), the
Priority Academic Program Development (PAPD) of Jiangsu
Higher Education Institutions, Soochow University Funds
(Nos. 14109001, Q410900510), Suzhou Industrial Park Fund,
and the National Science Foundation of USA (CHE-1266442)
for financial support.
−
Co(CO)4 onto the activated epoxide gives the ring-opened
intermediate. CO insertion affords an acyl-Co species. The
imine substrate then nucleophilically attacks the acyl-Co bond
to give the iminium intermediate. Intramolecular nucleophilic
cyclization between the alkoxide and the iminium gives the
product and regenerates the [LA]+[Co(CO)4]− species. In
catalytic cycle II, the imine coordinates to the Lewis acid first.
Nucleophilic addition of the epoxide substrate onto the
activated imine gives the oxonium intermediate, which
undergoes intramolecular nucleophilic addition followed by
CO insertion to afford an acyl-Co species. Intramolecular
nucleophilic cyclization between the amide group and the acyl
group gives the product and regenerates the [Lewis acid]+[Co-
(CO)4]− species. There is no experimental indication at this
point as to which mechanism or whether both are operative for
the reaction.
In conclusion, we have shown that the readily available
imines and epoxides can undergo selective cyclization along
with CO to form 1,3-oxazinan-4-ones. The reaction can be
catalyzed by the catalyst system composed of the commercially
available Co2(CO)8 and LiCl. We are currently exploiting the
synthetic utilities and investigating the mechanism of the
reaction.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Typical experimental procedures, full characterization of all new
1
compounds, and H and 13C NMR spectra for all substituted
1,3-oxazinan-4-one products. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: linshaohui@suda.edu.cn.
*E-mail: qpan@suda.edu.cn.
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