Ru3(CO)12-catalyzed reactions of catechols with alkynes: An atom-economic process for the synthesis of 2,2-disubstituted 1,3-benzodioxoles from the double addition of the O-H bond across a triple bond

Article abstract of DOI:10.1021/jo801633w

(Chemical Equation Presented) Ru₃(CO)₁₂ has been found to be the efficient catalyst for the addition reactions of catechols with both terminal and internal alkynes to selectively afford 2,2-disubstituted 1,3-benzodioxoles in good to high yields. The formation of 2,2-substituted 1,3-benzodioxoles results from the tandem addition of two O-H bonds of catechols to alkyne's triple bond.

Full text of DOI:10.1021/jo801633w

TABLE 1. Reaction of Phenylacetylene (1a) with Catechol (2a)
under Different Conditionsa
Ru3(CO)12-Catalyzed Reactions of Catechols with
Alkynes: An Atom-Economic Process for the
Synthesis of 2,2-Disubstituted 1,3-Benzodioxoles
from the Double Addition of the O-H Bond
Across a Triple Bond
entry
catalyst (mol %)
1a:2a
temp (°C)/time (h)
yield (%)b
1
2
3
4
5
6
ReBr(CO)5 (5)
ReBr(CO)5 (5)
Ru3(CO)12 (5)
Ru3(CO)12 (5)
Ru3(CO)12 (2)
Ru3(CO)12 (2)
1.0
3.0
3.0
1.2
1.1
1.1
110/20
150/20
150/20
120/12
100/12
80/12
<5
Ming Li and Ruimao Hua*
20
Department of Chemistry, Tsinghua UniVersity, InnoVatiVe
Catalysis Program, Key Laboratory of Organic
Optoelectronics & Molecular Engineering of Ministry of
Education, Beijing 100084, China
>99
>99
95
90 (84)
a Reactions were carried out with 1.0-3.0 mmol of 1a, 1.0 mmol of
2a, and 2-5 mol % of catalyst (relative to 2a) in 1.0 mL of toluene in a
sealed tube. b Yield according to GC based on the amount of 2a used.
The number in parentheses is isolated yield.
ruimao@mail.tsinghua.edu.cn
ReceiVed July 24, 2008
tylenedicarboxylate, which is an activated internal alkyne in the
presence of DABCO (1,4-diazabicyclo[2.2.2]octane).7
Table 1 shows the results of the reaction of phenylacetylene
(1a) with catechol (2a) under different reaction conditions. Our
initial attempts were directed toward the catalytic evaluation
of ReBr(CO)5 for the activation of the O-H bond of 2a and its
addition to alkyne, since our earlier work demonstrated that
ReBr(CO)5 was an efficient catalyst for the activation of the
O-H bond of carboxylic acids and its addition to terminal
alkynes.6b,c However, when a mixture of 1a with an equimolar
amount of 2a was heated in toluene in the presence of
ReBr(CO)5 (5 mol%) at 110 °C for 20 h, only a trace amount
of adduct was observed (entry 1). Increasing the reaction
temperature to 150 °C and using an excess amount of 2a (3
equiv) resulted in the formation of 2-methyl-2-phenyl-1,3-
Ru3(CO)12 has been found to be the efficient catalyst for the
addition reactions of catechols with both terminal and internal
alkynes to selectively afford 2,2-disubstituted 1,3-benzo-
dioxoles in good to high yields. The formation of 2,2-
substituted 1,3-benzodioxoles results from the tandem ad-
dition of two O-H bonds of catechols to alkyne’s triple
bond.
1,3-Benzodioxoles are one of the important classes of
heterocyclic compounds due to their existence in natural
products such as piperine,1 sesamol,2 and justicidin3 and having
diverse biological activities.4 The common synthetic methods
for construction of 1,3-benzodioxoles are focused on the
condensation of catechols with aldehydes or ketones in the
presence of various acidic catalysts.5
Development of atom-economic reactions in organic synthesis
is one of the important and challenging research areas. In
continuation of our interest in transition metal-catalyzed activa-
tion of the O-H bond and its addition reaction to alkynes,6 we
have designed and investigated the cyclic addition reactions of
catechols with alkynes to establish the efficient catalytic system
for the synthesis of 2,2-disubstituted 1,3-benzodioxoles, which
are expected to be promising starting materials to be converted
to the related analogues of 1,3-benzodioxole-containing com-
pounds for their biological studies.
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8658 J. Org. Chem. 2008, 73, 8658–8660
10.1021/jo801633w CCC: $40.75 2008 American Chemical Society
Published on Web 09/26/2008

TABLE 2. Ru3(CO)12-Catalyzed Reaction of 2a with Alkynesa
SCHEME 1. Proposed Mechanism for the Addition of
Catechols to Alkynes
corresponding 1,3-benzodioxoles in good to high isolated yields
at an elevated temperature (150 °C) (Table 2, entries 3-6). When
unsymmetrical internal alkynes were used, two adduct isomers
might form, and the ratio of isomers depends on the nature of
alkynes. 2-Ethyl-2-phenyl-1,3-benzodioxole (3h) could be regi-
oselectively isolated in 86% yield from the reaction of 1-phenyl-
1-propyne (1h) with 2a, and only a small amount of regioiosmer
(2-methyl-2-benzyl-1,3-benzodioxole) was found in the reaction
mixture, revealed by GC-MS analysis of the reaction mixture (Table
2, entry 7). However, in the cases of 1-phenyl-1-butyne (1i) and
1-phenyl-1-hexyne (1j) employed, the adducts 2-alkyl-2-phenyl-
1,3-benzodioxoles 3i and 3j, which were expected to form from
the same regioselective addition reaction as the reaction of 1h with
2a did, were formed as the minor products, and the predominant
products were their regioisomers 3i′ and 3j′ (Table 2, entries 8
and 9). All the regioisomers could be isolated analytically pure by
careful preparative TLC separation (silica, eluted with petroleum
ether). The reaction of methyl phenylpropiolate (1k) with 2a gave
3k as the exclusive adduct, in which the addition of H took place
at the carbon adjacent to the ester group (Table 2, entry 10).
a Reactions were carried out with 1.1 mmol of 1, 1.0 mmol of 2a,and
2 mol % of Ru3(CO)12 in 1.0 mL of toluene in a sealed tube for 12 h.
b Isolated yields.
benzodioxole (3a) in 20% GC yield (entry 2). The structure of
3a was characterized by its spectroscopic data, and it is apparent
that 3a results from the selective double Markovnikov addition
of 2a with 1a via activation of O-H bonds.
It is well-known that Ru3(CO)12 could efficiently catalyze
the addition reaction of carboxylic acids8 and diphenylphos-
phinic acid6a to terminal alkynes via cleavage of the O-H bond.
Therefore, the reaction of 1a with 2a was also examined in the
presence of Ru3(CO)12, and found that Ru3(CO)12 showed high
catalytic activity and selectivity for the cyclic addition reaction
of 1a with 2a to afford 3a in high yields (entries 3-6). The
analyses of the reaction mixtures disclosed that neither 1,4-
benzodioxan nor anti-Markovnikov adduct(s) were formed under
the reaction conditions.
To evaluate the generality of the present addition reaction, the
reactions of catechol (2a) with terminal and internal alkynes were
examined. As shown in Table 2, a number of 2,2-disubstituted 1,3-
benzodioxoles could be obtained by the addition reactions of 2a
with a variety of alkynes in the presence of Ru3(CO)12. Terminal
alkynes such as 4-(methylphenyl)acetylene (1b) and 1-heptyne (1c)
reacted with 2a at 100 °C to selectively afford 2-methyl-2-p-tolyl-
1,3-benzodioxole (3b) and 2-methyl-2-n-pentyl-1,3-benzodioxole
(3c) in 89% and 82% isolated yields, respectively (Table 2, entries
1 and 2). Symmetrical internal alkynes reacted with 2a to give the
In addition, catechols bearing the electron-donating group CH3
(2b) and electron-withdrawing group of NO2 (2c) could also
react with both terminal and internal alkynes smoothly to give
the corresponding adducts in high isolated yields.
The mechanism of the present addition of alkyne with
catechols is considered to be similar to those of the Ru3(CO)12-
catalyzed addition reaction of carboxylic acids and diphe-
nylphosphinic acid with alkynes.6a,8 Therefore, a proposed
mechanism is depicted in Scheme 1. It involves the tandem
activation of O-H bonds by the oxidative addition of the OsH
J. Org. Chem. Vol. 73, No. 21, 2008 8659

bond to ruthenium complexes9 and their intermolecular addition
to the CtC bond and subsequent intramolecular addition to the
CdC bond to afford 2-substituted 1,3-benzodioxoles 3.
In conclusion, we have established an atom-economic and
efficient method for the synthesis of 2,2-disubstituted 1,3-benzo-
dioxales in good to high yields via the tandem addition of two
O-H bonds of catechols to alkynes in the presence of Ru3(CO)12.
When terminal alkynes were used, the cyclic addition reactions
afforded Markovnikov adducts selectively, while the regioselectivity
in the reaction of unsymmetrical internal alkynes with catechols
depends on the structural nature of alkynes.
mmol), catechol (2a) (110.0 mg, 1mmol), Ru3(CO)12 (12.7 mg, 0.02
mmol), and toluene (1.0 mL) under nitrogen in a screw-capped
tube was heated with stirring at 80 °C for 12 h. After cooling, the
reaction mixture was diluted with CH2Cl2 to 3.0 mL, and n-
octadecane (38.1 mg, 0.15 mmol) was added as internal standard
material for GC analysis. After GC and GC-MS analyses, solvents
and volatiles were removed under vacuum, and the residue was
then purified by column chromatography (silica gel, eluted with
petroleum ether) to afford 3a (179.0 mg, 0.84 mmol, 84.0%) as a
yellow oil. GC analysis of the reaction mixture revealed that 3a
was formed in 90% yield. 3a: 1H NMR (300 MHz, CDCl3) δ
7.61-7.58 (m, 2H), 7.38-7.32 (m, 3H), 6.80-6.76 (m, 4H), 1.98
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 147.3, 141.3, 129.0, 128.5,
125.1, 121.5, 116.7, 108.8, 27.2; GCMS m/z (% rel intensity) 212
(M+, 68), 197 (100), 166 (2), 151 (3), 135 (12), 110 (67), 103 (69),
91 (4), 77 (27).
Experimental Section
Typical Experimental Procedure for Addition of Pheny-
lacetylene (1a) with 1,2-Benzenediol (2a) To Afford 3a (Table
1, entry 6): A mixture of phenylacetylene (1a) (112.3 mg, 1.1
Acknowledgment. This project (20573061) was supported
by the National Natural Science Foundation of China.
(8) (a) Rotem, M.; Shvo, Y. Organometallics 1983, 2, 1689–1691. (b) Rotem,
M.; Shvo, J. J. Organomet. Chem. 1993, 448, 189–204.
Supporting Information Available: General experimental
(9) The oxidative addition of the O-H bond of phenols is well-documented.
For selected examples, see: (a) Burn, M. J.; Fickes, M. G.; Hollander, F. J.;
Bergman, R. G. Organometallics 1995, 14, 137–150. (b) Cabeza, J. A.; Mart´ınez-
Garc´ıa, M. A.; Riera, V.; Garc´ıa-Granda, S.; Van der maelen, J. F. J. Organomet.
Chem. 1996, 514, 197–202. (c) Chuechill, M. R.; Keil, K. M.; Bright, F. V.;
Pandey, S.; Baker, G. A.; Keister, J. B. Inorg. Chem. 2000, 39, 5807–5816. (d)
Hirana, M.; Kurata, N.; Komiya, S. J. Organomet. Chem. 2000, 607, 18–26.
1
method, characterization data, and charts of H, 13C NMR for
all products. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO801633W
8660 J. Org. Chem. Vol. 73, No. 21, 2008