Convenient one-step construction of yne-functionalized aryl halides through domino cyclization from tetraynes

Article abstract of DOI:10.1039/c3cc47707j

An efficient method for the construction of fused yne-substituted aryl halides by reaction of unactivated linear tetraynes with allyl halides via domino C-C coupling and formation of C-X bonds in the presence of Pd(OAc) ₂/PPh₃ was de

Full text of DOI:10.1039/c3cc47707j

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Convenient one-step construction of
yne-functionalized aryl halides through
Cite this:DOI: 10.1039/c3cc47707j
domino cyclization from tetraynes†
Received 9th October 2013,
Accepted 13th January 2014
Hao Zhang, Qiong Hu, Lidong Li, Yimin Hu,* Pingping Zhou, Xiaorong Zhang,
Haifeng Xie, Fei Yin, Yadong Hu and Shaowu Wang*
DOI: 10.1039/c3cc47707j
www.rsc.org/chemcomm
An efficient method for the construction of fused yne-substituted aryl 5-exo- and 6-endo-dig hydroarylation from o-alkynyl biaryls as
halides by reaction of unactivated linear tetraynes with allyl halides starting materials.11 In our current work, we developed the first
via domino C–C coupling and formation of C–X bonds in the simple synthesis of aryl halides through tetrayne systems via
presence of Pd(OAc)2/PPh3 was developed.
domino cyclization.12 This process exhibits excellent regioselectivity
to produce highly substituted fused bicyclic 2,3-dihydro-1H-indene
Aryl halides have attracted considerable attention in organic synthesis under mild reaction conditions with good to excellent yields.
and their chemistry is being actively explored in synthetic transforma- We have studied the palladium-catalyzed reactions of dimethyl
tions.1 Fused aryl halides represent an interesting structural motif 2,2-bis(5-phenylpenta-2,4-diyn-1-yl)malonate (a–l) with different
frequently found in various bioactive molecules and functional allyl halides, which provide a direct, efficient, and economical
materials.2 Although numerous fused heterocycles containing halo- methodology for the construction of fused yne-functionalized
gens have been characterized and used in various applications, few aryl halides through successive C–C coupling patterns of the
reports on fused yne-functionalized aryl halides are available.3 This products with unexpected C–X coupling reactions.
may be partly due to the fact that these compounds cannot be
A survey of the reaction conditions using b and allyl bromide
prepared efficiently using current methods, the formation of as a test experiment was performed (Table 1). The efficiency of the
carbon–halogen bonds in complex molecules is still a significant domino reaction can be enhanced by increasing the reaction
challenge.4 Hoye reported a variety of hexadehydro-Diels–Alder temperature to 100 1C. The bases play an important role in the
(HDDA) cascade reactions to construct complex benzenoids overall efficiency of this domino reaction, by simply varying the
through aryne intermediates.5 Lee and co-workers developed bases from potassium carbonate to tributylamine under otherwise
catalytic alkane C–H insertion, forming carbon–carbon bonds, to identical conditions as well as furnishing the excited diethyl
convert tetrayne into yne-functionalized tricyclic compounds.6 7-bromo-5-phenyl-4-(phenylethynyl)-1H-indene-2,2(3H)-dicarboxylate
Ishihara developed a method for the halocyclization of homo- (ba) with 90% yield. Among the catalysts investigated, the
(polyprenyl)arenes using nucleophilic promoters.7 Hayashi reported palladium(II) acetate/PPh3 catalytic system was found to be the most
on the ruthenium-catalyzed transformation of aryl and alkenyl effective in the cross-coupling reactions screened, DMF proved to be
triflates to halides.8 As we know, fused arylhalides can be used a better solvent than toluene. If NaI or NaBr or Bu4NBr were used as
as substrates in the Heck reaction to design building blocks the halide source instead of allyl bromide, the reaction could not be
for pharmaceutically and biologically active substances.9,10 performed. If allyl chloride was used in combination with Bu4NBr
Both aromatics and acetylenes have been successfully used in (or allyl bromide with Bu4NCl) to provide the halogen species, the
extended p systems for organic electronic materials. The fluorene reactions provided the normal yne-functionalized aryl halides in
and phenanthrene frameworks are synthesized through exclusive which the halides came from allyl halides without any scrambling of
the halides in the products. Thus, the following standard reaction
conditions were used to carry out the following studies: 1 equiv.
Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Key
of b was reacted with 1.2 equiv. of allyl bromide and water in the
presence of 2 mol% of palladium(II) catalyst, and 4 mol% PPh3
with nBu3N (2 equiv.) as an additive in DMF at 100 1C.
Illustrative examples of the scope of this study are shown in
Table 1. Interestingly, various substituted tetraynes were compatible
with this palladium-catalyzed domino reaction. A range of 7-halide-5-
phenyl-4-(phenylethynyl)-1H-indene-2,2(3H)-dicarboxylate compounds
Laboratory of Molecular-Based Materials, School of Chemistry and Materials
Science, Anhui Normal University, Wuhu, Anhui 241000, China.
E-mail: yiminhu@mail.ahnu.edu.cn, swwang@mail.ahnu.edu.cn;
Fax: +86 553 388 3517; Tel: +86 553 386 9310
† Electronic supplementary information (ESI) available: Experimental procedures
and characterization of all new compounds. CCDC 901558–901560. For ESI and
crystallographic data in CIF or other electronic format see DOI: 10.1039/
c3cc47707j
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Table 1 Palladium-catalyzed domino reaction for the formation of fused
yne-functionalized aryl halides from tetraynesa
Entry
S
Y/R
X
Product Yieldb (%)
1
2
3
4
5
6
7
8
a
b
b
b
c
c
c
d
d
e
e
f
g
h
h
i
j
k
l
Y = C(COOMe)2; R = Ph
Y = C(COOEt)2; R = Ph
Y = C(COOEt)2; R = Ph
Br aa
Br ba
Cl bb
84
90
89
77
76
85
80
88
84
83
86
80
85
85
73
77
75
87
84
82
Y = C(COOEt)2; R = Ph
I
bc
Fig. 1 Molecular structure of hb with ellipsoids drawn at 50% probability.
Hydrogen atoms are omitted for clarity.
Y = (MeOC)C(COOEt); R = Ph
Y = (MeOC)C(COOEt); R = Ph
Y = (MeOC)C(COOEt); R = Ph
Y = C(COOiPr)2; R = Ph
Br ca
Cl cb
I
cc
Br da
Cl db
9
Y = C(COOiPr)2; R = Ph
10
11
12
13
14
15
16
17
18
19
20
Y = C(COOEt)2; R = p-MeOC6H4 Br ea
Y = C(COOEt)2; R = p-MeOC6H4 Cl eb
Y = C(COOiPr)2; R = p-MeOC6H4 Br fa
Y = C(COOEt)2; R = p-MeC6H4
Y = C(COOEt)2; R = p-EtOC6H4
Y = C(COOEt)2; R = p-EtOC6H4
Y = C(COOEt)2; R = p-FC6H4
Y = C(COOiPr)2; R = p-ClC6H4
Y = NTs; R = Ph
Br ga
Br ha
Cl hb
Br ia
Cl ja
Br ka
Br la
Cl lb
Y = NTs; R = nBu
Y = NTs; R = nBu
l
a
General conditions: a–l (1.0 equiv.), AllylX (X = Cl; Br; I) (1.2 equiv.), H2O
(1.2 equiv.), Pd(OAc)2 (2 mol%), PPh3 (4 mol%), nBu3N (2 equiv.), DMF
b
10 mL, 100 1C. Isolated yield after flash column chromatography.
were readily isolated with good to excellent yields when tetraynes
with a variety of substituted groups were employed. The substituted
groups could be methoxy, methyl, ethyl, bromo, or chloro groups.
Using substituted tetraynes (c, d, e, g) as substrates with allyl
chloride or allyl bromide or allyl iodide, the reactions afforded
7-halo-5-phenyl-4-(phenylethynyl)-1H-indene-2,2(3H)-dicarboxylate
in good yields (Table 1, for example, cb, da, eb and ga). The
Scheme 1
In summary, we have developed an easy method to construct
compounds ba and bb had the highest isolated yields, 90% and fused yne-functionalized aryl halides through tetrayne systems via
89%, respectively. Moreover, the cyclic compound ka from reaction domino cyclization. This reaction exhibited an excellent regio-
of 4-methyl-N,N-bis(5-phenylpenta-2,4-diyn-1-yl)benzenesulfonamide selectivity, producing highly substituted fused yne-functionalized
(k) and allyl bromide also has a high yield (Table 1, entry 18) of 87%. bicyclic compounds under mild reaction conditions with good to
Substrates containing alkyl groups (Table 1, entries 19, 20) instead excellent yields in the presence of the amine and palladium(II)
of phenyl or substituted phenyl groups also produced good yields. acetate/PPh3 catalytic system. To the best of our knowledge, no
All new products were fully characterized by various spectro- study on such fused benzene halide cores has been reported
scopic techniques and high-resolution mass spectrometry, and the with this methodology, a topic which could be of interest
molecular structures of ba, bb and hb (Fig. 1), were confirmed using among researchers in the field. The generality of this process
single-crystal X-ray analyses (see the ESI† for details).13
also makes the reaction highly valuable due to the synthetic
A plausible mechanism for the formation of fused yne- and medicinal importance of these unsaturated polycyclic
functionalized aromatic halides is depicted in Scheme 1. Oxidative compounds. This preliminary work has broad implications
coupling of Pd(0) in the tetrayne moiety (1) produces the Pd(II) and may serve as a seminal study toward the catalytic synthesis
intermediate A, A generates a seven-member ring, B. B undergoes of aromatic halides with unactivated olefins. In addition, the
reductive elimination coupling to afford Pd(0) (C),14 C then reacts construction of the C–X bond followed by successive C–C
with allylic bromide and H2O15 to produce D, which undergoes coupling may have potential application for direct halogenation
reductive elimination to produce the final products and Pd(0).
of unsaturated hydrocarbons. Further mechanistic studies and
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The authors thank the National Natural Science Foundation of
China (21272005, 21072003, 21372010), National Basic Research
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Human Resources of Anhui Province for financial support.
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deuterated product was observed, indicating that DMF did not
take part in the reaction. A deuterated product was isolated when
the reaction was performed with a mixed solvent of DMF and a
small amount of deuterated water (D2O) (comparison of 1H NMR of
la with lc, see ESI†).
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