Synthesis of 3-pyrrolin-2-ones by rhodium-catalyzed transannulation of 1-sulfonyl-1,2,3-triazole with ketene silyl acetal

Article abstract of DOI:10.1021/ol501514b

α-Imino rhodium carbenoids generated from 1-sulfonyl 1,2,3-triazole were applied to the 3 + 2 cycloaddition with ketene silyl acetal, offering a novel and straightforward synthesis of biologically interesting compound 3-pyrrolin-2-one with broad substrate scope.

Full text of DOI:10.1021/ol501514b

Letter
pubs.acs.org/OrgLett
Synthesis of 3‑Pyrrolin-2-ones by Rhodium-Catalyzed
Transannulation of 1‑Sulfonyl-1,2,3-triazole with Ketene Silyl Acetal
Rui-Qiao Ran, Jun He, Shi-Dong Xiu, Kai-Bing Wang, and Chuan-Ying Li*
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha West Higher Education District, Hangzhou 310018, China
S
* Supporting Information
ABSTRACT: α-Imino rhodium carbenoids generated from 1-
sulfonyl 1,2,3-triazole were applied to the 3 + 2 cycloaddition
with ketene silyl acetal, offering a novel and straightforward
synthesis of biologically interesting compound 3-pyrrolin-2-
one with broad substrate scope.
3-Pyrrolin-2-ones, closely related to pyrroles, are not only useful
building blocks for the construction of pyrroles or γ-lactam
derivative,1 but also core structures of bioactive natural products
and pharmaceuticals (Figure 1).2 Several methods have been
equilibrium between triazoles and their diazoimine tautomers, no
slow-addition techniques or multifold triazoles were needed in
the transformation.10,11 More importantly, due to the high
nucleophilic character of the nitrogen atom, α-imino carbene
behaves as a 1,3-dipole equivalent to react with diverse
unsaturated compounds.12,13 In view of the prevalence of
nitrogen-containing heterocycles in pharmaceuticals and bio-
logically relevant molecules, this method is of great important
since it offers new opportunities for construction of function-
alized N-heterocycles. Very recently, the group of Lee developed
an interesting approach for the synthesis of pyrroles.12q In the
reaction, alkenyl alkyl ethers were employed to trap the α-imino
carbenoid, and the products were obtained via the facile
elimination of alcohols from dihydropyrroles. We have been
interested in carbene chemistry for a long time,14 and we
envisioned that simply changing the position of the double bond,
compound 1 can be transformed to compound 2, which is
reasonably broken down into two key synthons A and B (Scheme
1). We set up a leaving group in synthon B in order to reserve the
carbonyl group, so the ketene silyl acetal was used as the
synthetic equivalent. Although electron-rich olefins acting as the
dipolarophiles in this chemistry have been reported,12n,q,13c the
formation of the amide group in the 3 + 2 cycloaddition is
unusual.
Figure 1. Natural compounds with 3-pyrrolin-2-one skeletons.
reported to access this useful structure, notably reduction of
maleimide,3 oxidation of pyrrole or pyrrole-2-carboxaldehyde,4
reductive cyclization of β-cyanoesters,5,2b condensation of
ketoamides, etc.6 However, each of the above methods has its
respective limitations (poor regioselectivity, not easily available
starting materials, multiple steps, harsh conditions, etc.). Herein,
we report an efficient and versatile process that constructs 3,4-
disubstituted 3-pyrrolin-2-ones from easily accessible 1-sulfonyl-
1,2,3-triazole and ketene silyl acetals.
Scheme 1. Initial Hypothesis
In 2007, Gevorgyan and co-workers reported an efficient Rh-
catalyzed transannulation of pyridotriazoles with alkynes and
nitriles.7 Substituted pyridotriazoles were used as precursors of
rhodium carbenoids and were converted into pyrrolopyridines
and imidazopyridines. In 2008, Gevorgyan and Fokin demon-
strated that readily available 1-sulfonyl 1,2,3-triazoles8 can
decompose to α-imino carbenoid, which underwent formal 3 +
2 cycloaddition with nitriles to afford imidazoles.9 Owing to the
Received: May 27, 2014
© XXXX American Chemical Society
A
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Letter
a
a
Table 1. Optimization of Reaction Conditions
Table 2. Reaction Scope
a
0.2 mmol of triazole 3a and 0.36 mmol of ketene silyl acetal 5a were
used; the reaction was carried out in 2 mL of solvent under N2, DCE =
b
c
1,2-dichloroethane. Yield of isolated products. 97% of 3a was
d
e
recovered. 78% of 3a was recovered. 98% of 3a was recovered.
To test this hypothesis, we began our study using readily
available ketene silyl acetal 5a and triazole 3a. Gratifyingly,
treatment of 3a with 1.8 equiv of 5a in the presence of Rh2(Oct)4
afforded 3-pyrrolin-2-one 1aa in 83% yield (Table 1, entry 1).
Attempts to improve this reaction by screening other catalysts
revealed that Rh2(OAc)4 was a better catalyst (entry 2). When we
examined the solvent effects (entries 7−9), we found that DCE
gave the best yield of 1aa (93%). Reaction temperature is a key
factor in triazole decomposition, and temperatures higher or
lower than 80 °C only led to decreased yield (entries 10−13).
Without Rh2(OAc)4, 98% of the triazole was recovered after 12 h
(entry 14).
a
In the presence of 0.002 mmol of Rh2(OAc)4, 0.2 mmol of triazole 3
b
and 0.36 mmol of 5 were reacted in 2 mL of DCE under N2. Yield of
isolated products, average of two runs.
It has been reported by Tang11k that an aryl group on the aryl
sulfonyl azide impacted the reactivity of the triazole and the
resulting carbene. The scope of the reaction was subsequently
examined by first varying the sulfonyl group. As seen from the
results compiled in Table 2, the electronic and steric properties
have great impact on the yield (entries 1−6). Alkylsulfonyl
substituted triazole 3b and 3g afforded the corresponding
products in moderate yield (entries 1 and 6). Substrates with
electron-rich aryl groups at the sulfonyl substituent led to 1ad
and 1ae with high yield, while 1ac was obtained in only 55% yield
(entry 2). Notably, the reactions maintained satisfactory
efficiency with substrates 3h-3p containing a variety of functional
groups including methoxy, fluoro, bromo, trifluoromethyl,
methoxycarbonyl, and thienyl, the corresponding products
1ah−ap were obtained in 64−91% yields. Finally, we focused
our attention on the variation of the ketene silyl acetals.
Compounds 5d and 5e bearing aryl group also afforded the
desired products, albeit in moderate yield (entries 19 and 20).
Relatively higher yields were obtained when alkyl ketene silyl
acetals were employed (entries 16−18).
mechanism to rationalize the formation of 1ba is proposed. The
equilibrium is intercepted by Rh2(OAc)4 to afford highly
electrophilic α-imino rhodium carbenoid D (Scheme 2), which
Scheme 2. Proposed Mechanism
When triazole 3a was treated with dirhodium acetate at 80 °C
in the presence of 5b, 3-pyrrolin-2-one 1ba was obtained in 66%
yield after 16 h (Table 2, entry 16). However, if we quenched the
reaction when TLC analysis showed that triazole was just
completely consumed (3.6 h), compounds 6 could be isolated in
40% yield (eq 1). On the basis of these experiments, a plausible
is attacked by 5b to give rise to intermediate E (path a).
Subsequent intramolecular nucleophilic addition of the nitrogen
of the imino group would result in the formation of heterocyclic
compound F, which undergoes elimination of MeOTMS and
migration of carbon carbon double bond to afford 3-pyrrolin-2-
one 1ba. In another pathway, cyclopropane H is formed and
B
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Letter
collapses into stabilized zwitterionic intermediate I or J, which
also leads to the formation of F by intramolecular nucleophilic
addition. In the NMR studies, cyclopropane H was not observed
and compound F was detected as a mixture of diastereoisomers
(see the Supporting Information for more details). However,
since we can isolate compound 6 in 40% yield (eq 1),
cyclopropane H should be one of the key intermediates in this
reaction. We believe the reason we can not detect H is that this
donor−acceptor cyclopropane is not stable under the reaction
conditions, compound F is obtained by rearrangement and
compound 6 is formed via reaction with water. Thus, both of
these two pathways are possible.
Moreover, since the triazole and the ketene silyl acetal deliver
each of the two substituents of the products, this strategy offers
much synthetic flexibility in comparison with the traditional
methods.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, characterization data, and NMR
spectra for new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
Notably, the corresponding γ-lactam 7 could be easily
obtained by hydrogenation of compound 1aa with 10% Pd/C
under 6 atm of H2 (eq 2). Suzuki coupling of 1cn and PhB(OH)2
*E-mail: licy@zstu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was generously supported by the National Natural
Science Foundation of China (21002091, 21372204) and
Zhejiang Sci-Tech University 521 project.
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