Manganese-catalyzed benzene synthesis by [2+2+2] coupling of 1,3-dicarbonyl compound and terminal acetylene

Article abstract of DOI:10.1021/ja8015186

Treatment of a mixture of a 1,3-dicarbonyl compound such as a β-ketoester or 1,3-ketone and a terminal acetylene with a catalytic amount of MnBr(CO)₅ in heated toluene produces a benzene derivative by a [2+2+2] coupling reaction incorporating the enol part of the dicarbonyl compound and two moles of the acetylene. When the reaction was carried out using phenylacetylene derivatives, the reaction was completely regioselective, producing p-terphenyl compounds in good to excellent yield. Aliphatic terminal acetylenes also reacted readily but gave a mixture of regioisomers. The reaction features high atom economy, neutral conditions, and functional group tolerance, and will be useful for materials-oriented studies. Copyright

Full text of DOI:10.1021/ja8015186

Published on Web 05/24/2008
Manganese-Catalyzed Benzene Synthesis by [2+2+2] Coupling of
1,3-Dicarbonyl Compound and Terminal Acetylene
Hayato Tsuji,* Ken-ichi Yamagata, Taisuke Fujimoto, and Eiichi Nakamura*
Department of Chemistry, The UniVersity of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received February 28, 2008; E-mail: tsuji@chem.s.u-tokyo.ac.jp; nakamura@chem.s.u-tokyo.ac.jp
Scheme 1
We report here a new reaction, manganese-catalyzed intermo-
lecular dehydrative [2+2+2] coupling of one mole of a 1,3-
dicarbonyl compound and two moles of a terminal acetylene, which
produces a benzene derivative in good to excellent yield (Scheme
1). When phenylacetylene derivatives (R3 ) aryl) are employed,
the reaction provides a synthetically useful, modular approach to
p-terphenyl derivatives. The reaction formally resembles the well-
known [2+2+2] alkyne trimerization approach to the synthesis of
benzene derivatives,1–3 but differs significantly in that the enol form
of the dicarbonyl compound is incorporated into the benzene ring
with expulsion of one mole of water. p-Terphenyl derivatives are
important building blocks for the synthesis of organic materials,4,5
and their selective synthesis has generally been achieved by group
10 metal-catalyzed cross-coupling of aryl metals and aryl halides.
The present reaction provides a new alternative to this conventional
methodology.
Scheme 2
We discovered this reaction serendipitously during our study of
the indium-catalyzed reaction of 1,3-dicarbonyl compounds with
1-alkynes.6 Extensive experimentation was necessary to optimize
the reaction conditions, when a mixture of ethyl acetoacetate and
3 equiv of phenylacetylene was heated to 65 °C in toluene in the
presence of 10 mol % MnBr(CO)5 (Scheme 2). Initially, the reaction
formed a mixture of three compounds in low yield: a p-terphenyl
ester 1, the corresponding carboxylic acid derivative of 1, and a
cyclohexadienol 2 that is a precursor of 1. When we increased the
reaction time, the amount of acid byproduct increased at the expense
of 1. This observation suggested that water generated during the
in situ conversion of 2 to 1 caused acid formation. To assist this
conversion as a separate step after cycloaddition, we treated the
reaction mixture with a catalytic amount of TsOH to obtain 1. This
procedure increased the yield to 46%. We then examined various
other additives, some of which further improved the yield. For
instance, AgBF4 and N-methylmorpholine N-oxide (NMO)7 in-
creased the yield to 75% and 79% yield, respectively, presumably
by activation of the catalyst through ligand exchange. Addition of
anhydrous MgSO4 (20 mol %) further improved the yield to 87%,
most likely by trapping water in situ. Other transition metal
complexes, such as Mo(CO)6, W(CO)6, ReBr(CO)5,8 FeI2(CO)4,
[RuCl2(CO)3]2, Co2(CO)8, Rh(acac)(CO)2, and IrCl(CO)(PPh3)2
were ineffective.
The scope of the reaction was examined and the results are in
Table 1. The reaction was found to be sensitive to the steric and
electronic effects of the R1 group. Ethyl acetoacetate reacted with
phenylacetylene to afford the p-terphenyl product in 87% yield
(entry 1), while the benzyl and allyl esters reacted similarly (84%
and 81%, respectively, in entries 2 and 3). Substrates bearing a
sterically demanding R1 substituent, cyclohexyl and tert-butyl
groups, did not afford any product at all (entries 4 and 5). Ethyl
benzoylacetate (R1 ) Ph), on the other hand, furnished the expected
product in 94% yield (entry 6). An electron-donating substituent
(entry 7) afforded the expected product in somewhat lower yield
Table 1. The Synthesis of 1 from Various 1,3-Dicarbonyl
Compounds (R1 ) Alkyl, Aryl, or Alkenyl, R2 ) Ester or Acyl) and
Phenylacetylenea
a The reaction was carried out using 3 equiv of phenylacetylene in
the presence of 10 mol % of MnBr(CO)5, 10 mol % of NMO, and 20
mol % of anhydrous MgSO4 in toluene at 65 °C. b The yield is based on
isolated material. c The reaction was carried out without MgSO4.
d Obtained as a mixture of regioisomers (18% R1 ) Ph, R2 ) COMe;
15% R1 ) Me, R2 ) COPh).
(75%). A γ,δ-unsaturated ꢀ-ketoester reacted readily with retention
of the conjugated R1 group giving a highly functionalized stilbene
derivative in 83% yield (entry 8, structure in Scheme 3 below).
1,3-Diketones gave mixed results. Pentane-2,4-dione was found
to be an excellent substrate and produced the desired benzene
derivatives in quantitative yield (entry 9). 1-Phenylbutane-1,3-dione,
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10.1021/ja8015186 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
Aliphatic acetylenes took part in the reaction readily, but regiose-
lectivity in the products was low. 1-Octyne and 3-phenylpropyne
afforded a 73:27 and 74:26 mixture of regioisomers in 94% and
82% yield, respectively (entries 7 and 8).9 On the basis of the NMR
analysis, the major isomer was assigned as a para isomer, and the
minor isomer tentatively as a meta isomer (Supporting Information).
In conclusion, we have developed an efficient method for the
synthesis of substituted benzene derivatives using a new manganese-
catalyzed dehydrative cycloaddition reaction of 1,3-dicarbonyl
compounds and terminal alkynes. This reaction has several syntheti-
cally attractive features: the use of naturally abundant and nontoxic
manganese metal as a catalyst,10 an interesting mode of participation
of the enol form of a 1,3-dicarbonyl compound in benzene synthesis,
good atom economy, good functional tolerance, high regioselectivity
of terphenyl formation and diverse structural variation in the
product. The structures of the terphenyl products illustrated below
suggest that such products will serve as useful starting materials
for modular syntheses of larger conjugation arrays useful for
materials applications.11 At present we do not have enough
experimental evidence to discuss the reaction mechanism. This will
be the subject of further studies.
Table 2. The Synthesis of 1 from Ethyl Benzoylacetate (R1 ) Ph,
R2 ) CO2Et) and Various Terminal Alkynes (R3 ) Aryl or Alkyl)a
Acknowledgment. This research was supported by KAKENHI
provided by MEXT/JSPS (to E.N., Grant No. 18105004) and the
Global COE Program for Chemistry Innovation. We thank L. Ilies
for some experiments.
Supporting Information Available: Detailed experimental proce-
dure and properties of compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
a The reaction was carried out using 3 equiv of alkyne in the
presence of 10 mol % of MnBr(CO)5, 10 mol % of NMO, and 20 mol
% of anhydrous MgSO4 in toluene at 65 °C. b The yield is based on
isolated material. c Ratio was determined by 1H NMR analysis.
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