Ruthenium-catalyzed decarbonylative addition reaction of anhydrides with alkynes: A facile synthesis of isocoumarins and α-pyrones

Article abstract of DOI:10.1039/c5cc03311j

A novel ruthenium catalyzed straightforward and efficient synthesis of isocoumarin and α-pyrone derivatives has been accomplished by the decarbonylative addition reaction of anhydrides with alkynes under thermal conditions.

Full text of DOI:10.1039/c5cc03311j

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Ruthenium-catalyzed decarbonylative addition
reaction of anhydrides with alkynes: a facile
synthesis of isocoumarins and a-pyrones†
Cite this:DOI: 10.1039/c5cc03311j
Received 21st April 2015,
Accepted 7th May 2015
Rashmi Prakash, Kommuri Shekarrao, Sanjib Gogoi* and Romesh C. Boruah*
DOI: 10.1039/c5cc03311j
www.rsc.org/chemcomm
Table 1 Optimization of the reaction conditions for 3aa
A novel ruthenium catalyzed straightforward and efficient synthesis
of isocoumarin and a-pyrone derivatives has been accomplished by
the decarbonylative addition reaction of anhydrides with alkynes
under thermal conditions.
Entry
Catalyst (2.5 mol%)
Solvent
3ab (%)
Isocoumarins and a-pyrones are the key scaffolds of various
natural products that show a wide range of exciting biological
activities.1 Some of the a-pyrones exhibit very interesting
fluorescence properties2a and they are proved to be bacterial
signaling molecules.2b
The transition metal catalyzed decarbonylative addition of
anhydrides and alkynes to construct oxygen containing hetero-
cycles is very rare in the literature. The only methodology
known so far for such a type of tandem reaction of anhydrides
and disubstituted alkynes to synthesize biologically important
isocoumarins and a-pyrones was reported by Matsubara and
coworkers using Ni(cod)2 (10 mol%) catalyst in the presence of
1
2
3
4
5
6
7
8
9c
RuCl3ÁxH2O
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
tAmOH
14
19
57
13
43
83
61
53
81
[RuCl2(PPh3)3]
[RuCl2(p-cymene)]2
Pd(OAc)2
[(Cp*RhCl2)2]
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
DCE
DMF
tAmOH
a
Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), catalyst (2.5 mol%),
b
solvent (3.0 mL), 100 1C, 24 h, unless otherwise mentioned. Isolated
yields. 5.0 mol% of catalyst.
c
Lewis acid ZnCl2 (20 mol%) and the ligand PMe3 (40 mol%).3 with disubstituted symmetrical alkynes is very regioselective in
Herein, we describe that [RuCl2(p-cymene)]2 (2.5 mol%) alone this Ru catalyzed reaction.
can catalyze the decarbonylative addition reaction of anhydrides
We started our studies by optimizing the reaction conditions
and alkynes to afford good yields of isocoumarins and a-pyrones for the decarbonylative annulation reaction of anhydride 1a
(Scheme 1). The scope of the Ru catalyzed decarbonylative with tolane 2a for the synthesis of 3a (Table 1). At the outset,
addition reaction could be broadened efficiently to a wide range different metal catalysts were screened as shown in Table 1
of anhydrides and alkynes. It is noteworthy to say that the and [RuCl2( p-cymene)]2 turned out to be the optimal catalyst in
decarbonylative addition reaction of unsymmetrical anhydrides 1,4-dioxane (entries 1–5). Among a set of representative solvents
surveyed for this reaction (entries 6–9), the highest yield (83%)
was obtained using tAmOH as the solvent (entry 6). The reactions
performed in the presence of commonly used oxidants Cu(OAc)2,
CuBr2, AgOAc or in the presence of the additive AgSbF6 could
not further improve the yield of 3a (not shown in Table 1). With
the optimized reaction conditions in hand, we first tested its
scope in the decarbonylative annulation reaction of anhydride 1a
Scheme 1 Ru catalyzed decarbonylative addition reaction.
with functionalized diaryl-substituted alkynes (2b–e). We were
delighted to observe that the diaryl-substituted alkynes bearing
valuable electron-donating and electron-withdrawing groups in
the phenyl ring were well tolerated to provide 74–82% yield of
isocoumarins 3b–d. The dialkyl-substituted alkynes were also
found to be suitable substrates to furnish the desired products
Medicinal Chemistry Division, CSIR-North East Institute of Science and Technology,
Jorhat 785006, India. E-mail: skgogoi1@gmail.com, rc_boruah@yahoo.co.in;
Fax: +91 3762370011; Tel: +91 3762372948
† Electronic supplementary information (ESI) available: Experimental proce-
dures, characterization data, and 1H and 13C NMR spectra of new compounds.
See DOI: 10.1039/c5cc03311j
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Table 2 Synthesis of various substituted isocoumarinsa
3e and 3f in 77–78% yield. Moreover, the annulation reaction of
the alkyne substituted with a heterocyclic ring proceeded well to
provide the corresponding isocoumarin derivative 3g in 65%
yield. The unsymmetrically substituted alkynes also proved to be
good substrates for the decarbonylative annulation reaction and
several unsymmetrical alkynes substituted with aryl, heteroaryl
and alkyl substituents were reacted with 1a. The annulation
reaction between 1a and the unsymmetrical alkynes 2h, 2i and 2j
afforded a mixture of isocoumarins 3h–j (B1 : 1) in 67–83%
yield. Notably, the annulation reaction between 1a and the
unsymmetrical alkynes 2k and 2l was highly regioselective to
afford the products 3k5 and 3l in 76–79% yield. Anhydrides,
bearing electron-donating or -withdrawing groups on the phenyl
ring 1b–c, reacted regioselectively with alkynes 1a and 1l to
provide the products 3m–o in good yields (69–77%). The for-
mation of products 3k–m indicated the initial formation of the
C–C bond of the phenyl ring carbon with the alkyne carbon
bearing the alkyl substituent leading to the formation of the
highly regioselective products. The observed alkyne insertion
regiochemistry of 3k–m was similar to the previously reported
nickel,4a cobalt4b and palladium4c catalyzed carbocyclization
reaction, where the insertion of alkynes into carbon–metal
bonds occurred with the carbon atom generally attacking the
more positive carbon of the alkyne.4 Next, the annulation
reaction was tested with maleic anhydride 1d. As shown in
Table 3, symmetrical alkynes substituted with aryl, heteroaryl
and alkyl substituents turned out to be better substrates for
this annulation reaction and they provided a-pyrones 4a–e in
69–89% yield under the standard reaction conditions. The
reaction of 1d and unsymmetrical alkyne 2k provided an easily
separable mixture of a-pyrones 4f and 4g (4f : 4g = 3 : 1) in 89%
yield. The reaction of unsymmetrical anhydride 1e and sym-
metrical alkyne 2a was highly regioselective under the standard
conditions to provide a-pyrone 4h5 in 79% yield. In addition,
the 3,4-disubstituted maleic anhydrides 1f–g were converted to
pyrones 4i–j in 78–83% yield. The reaction of 1a with terminal
alkyne p-tolylacetylene, under the optimized reaction conditions,
provided the dimeric product (Z)-1,4-di-p-tolylbut-1-en-3-yne of
the alkyne.6 The reaction of 1a with 2,3-dimethyl-1,3-butadiene
or cyclohexylallene, under the optimized reaction conditions,
provided a complex mixture of products. The regioselectivity of
the products was proved by the comparison of new spectral and
physical data with those reported in the literature and from their
NOE spectra (Table 2).5
a
Reaction conditions: anhydride (1.0 mmol), alkyne (1.0 mmol) and the
Ru-catalyst (2.5 mol%) in tert-amyl alcohol (3.0 mL) were heated at
100 1C for 24 h under air; isolated yields.
Table 3 Synthesis of various substituted a-pyronesa
a
Reaction conditions: anhydride (1.0 mmol), alkyne (1.0 mmol) and the
Ru-catalyst (2.5 mol%) in tert-amyl alcohol (3.0 mL) were heated at
100 1C for 24 h under air; isolated yields.
Based on our findings and the previous results on ruthenium
metal catalyzed functionalization of carbon–oxygen bonds,7 as
well as on the transition metal catalyzed decarbonylative annula-
tion reactions,3,8 a plausible mechanism for the formation of 3 is
proposed, which is shown in Scheme 2. Oxidative addition of the
ruthenium catalyst to the anhydride O–CO bond produces six-
membered ruthenium cycle 5a. Decarbonylation of 5a and
subsequent insertion of alkyne 2 to the C–Ru bond generates
Scheme 2 Proposed mechanism (L = p-cymene).
seven-membered ruthenium cycle 5c, which on reductive (hard acid) with the alcohol (hard base), which increases the
elimination affords 3 and reinstates the starting Ru catalyst. stability of the ruthenium complexes.
The improved yield of 3a in tert-amyl alcohol might be due to
In summary, we have described the first example of the ruthe-
the electrostatic interaction between the ruthenium species nium catalyzed decarbonylative addition reaction of anhydrides with
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2 (a) K. Hirano, S. Minakata, M. Komatsu and J. Mizuguchi, J. Phys.
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The highly regioselective decarbonylative addition reaction of
unsymmetrical anhydrides and disubstituted symmetrical alkynes,
a broad substrate scope, simple experimental procedures, low
catalyst loading and high yield of products are the noteworthy
features of this reaction.
The authors thank CSIR, New Delhi, for the financial support on
the CSIR-ORIGIN (CSC-0108) and CSIR-ACT (CSC-0301) projects.
We are grateful to the Director, CSIR-NEIST, for his keen interest.
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