Gold-catalyzed cascade cycloisomerization of 1,7-diyn-3,6-bis(propargyl carbonate)s: Stereoselective synthesis of naphtho[b]cyclobutenes

Article abstract of DOI:10.1039/c3cc44757j

Gold-catalyzed cycloisomerization of 1,7-diyn-3,6-bis(propargyl carbonate)s leads to a highly efficient and diastereoselective synthesis of functionalized naphtho[b]cyclobutenes. A cascade sequence involving gold-catalyzed double 3,3-rearrangement, 6π-electrocyclic reaction and a decarbonylative cyclization was proposed for this reaction.

Full text of DOI:10.1039/c3cc44757j

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Gold-catalyzed cascade cycloisomerization
of 1,7-diyn-3,6-bis(propargyl carbonate)s:
stereoselective synthesis of naphtho[b]cyclobutenes†
Cite this: Chem. Commun., 2013,
49, 8650
Received 25th June 2013,
Accepted 23rd July 2013
Ming Chen, Jun Liu, Lu Wang, Xiaobo Zhou and Yuanhong Liu*
DOI: 10.1039/c3cc44757j
www.rsc.org/chemcomm
Gold-catalyzed cycloisomerization of 1,7-diyn-3,6-bis(propargyl carbo-
nate)s leads to a highly efficient and diastereoselective synthesis of
functionalized naphtho[b]cyclobutenes. A cascade sequence involving
gold-catalyzed double 3,3-rearrangement, 6p-electrocyclic reaction and
a decarbonylative cyclization was proposed for this reaction.
Benzocyclobutenes and naphthocyclobutenes are highly strained
aromatic compounds which attracted considerable interest because
of their unique structural features1 and their versatility in organic
synthesis.2 For example, benzocyclobutenes can act as efficient
precursors for the generation of o-quinodimethane intermediates
via thermal electrocyclic ring-opening reaction, which have been
widely utilized as diene counterparts in Diels–Alder reactions for
the construction of polycyclic molecules such as alkaloids, steroids,
terpenes, anthracyclines, lignanes and polyacenes, etc.2 Compared
Scheme 1 Synthesis of naphtho[b]cyclobutenes.
with the chemistry of benzocyclobutenes, there are only limited 1,6-diynyl carbonates to benzo[b]fluorenes,7 which is initialized
reports on the synthesis and reactivity of naphthocyclobutenes.3,4 through the formation of an allenyl carbonate via 3,3-rearrangement
Most of the synthetic routes to naphthocyclobutenes rely on the reaction. Our results also suggest that when propargyl carbonates
intramolecular [2+2] cycloaddition of benzene-bridged diallenes are employed instead of acetates, it is possible to form a more stable
which are generated by treatment of various bis(propargyl alcohol)s oxocarbenium ion intermediate, which can be further attacked by
with SOCl2 (ref. 4a and b) or HX,4b,c or through the [2,3]-sigmatropic nucleophiles. Inspired by this result, we postulated that the efficient
rearrangement of the in situ formed propargyl sulfenates4d or generation of the bisallenic intermediates might be achieved
phosphinites4e (representative reactions are shown in Scheme 1). through transition metal-catalyzed reactions of bis(propargyl
A Pd(0)/SmI2 mediated formation of naphthocyclobutenes from carbonate)s. Along these lines, we have developed a new route
o-bis(a-acetoxypropargyl)benzene has also been established.5 to obtain linear acenes via palladium-catalyzed reaction of
Although some progress has been achieved, the reaction involving 1,7-diyn-3,6-bis(propargyl carbonate)s with organoboronic acids
a stereoselective process is quite rare. On the other hand, in recent in which the bis[(s-allenyl)palladium(II)] and 2,3-naphthoquino-
years, gold-catalyzed 3,3-rearrangement reactions of propargyl dimethane intermediates might be involved.8 We next became
carboxylates have been proved as useful strategies for obtaining interested in the potential cyclization reactions of bis(propargyl
rapid access to a wide range of functionalized structural motifs.6 carbonate)s catalyzed by gold. Herein we report our investigation
Recently, we have developed a gold-catalyzed cyclization of of the gold-catalyzed cyclization of bis(propargyl carbonate) 1 to
synthetically valuable naphtho[b]cyclobutene 2 with excellent
cis-stereoselectivity (Scheme 1). The reaction likely proceeded
through the generation of bis(allenyl carbonate) as a key inter-
mediate via double 3,3-rearrangement followed by subsequent
cyclization. To our knowledge, this type of reaction mode has not
been reported in gold-catalyzed transformations.9
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Ling ling Lu, Shanghai 200032,
P. R. China. E-mail: yhliu@mail.sioc.ac.cn
† Electronic supplementary information (ESI) available: Experimental details,
NMR spectra of all new products, and X-ray crystallography of compounds 2f
and the trans-isomer of 3. CCDC 943600 (2f) and 943601 (the trans-isomer of 3).
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c3cc44757j
To test the hypothesis, the substrates of dicarbonates 1a-1 to
1a-3 bearing different protection groups, which were easily
c
8650 Chem. Commun., 2013, 49, 8650--8652
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prepared from phthalaldehyde as a diastereomeric mixture,8 PPh3AuCl or AgSbF6 alone did not give the desired product
were chosen to establish the reaction conditions. The results (entries 11 and 12). The use of Brønsted acid such as TfOH
are shown in Table 1. In light of the superior catalytic activity of afforded a complex mixture (entry 13).10 Allyl carbonate 1a-3
[Johnphos(MeCN)Au]SbF6 (catalyst A) in the efficient transfor- was also compatible under the catalysis of PPh3AuNTf2 or
mation of mono-propargyl carbonates,7 we first examined the PPh3AuSbF6, leading to the formation of 2a in 81% and 84%
reaction of bis(propargylic methyl carbonate) 1a-1 using gold(I) yields, respectively (entries 14 and 15). Notably, the results
complex A as the catalyst. However, the starting material demonstrated that the cyclization process is highly diastereo-
remained largely unchanged in toluene at room temperature selective, as only cis-2a was obtained in all cases.
(Table 1, entry 1). Further optimization indicated that the use of
Next, we proceeded to investigate the scope of this cyclo
PPh3AuNTf2 led to the formation of cis-naphtho[b]cyclobutene isomerization in terms of alkyne substituents. During this
2a with a cyclic carbonate structure in 47% yield at room process, we found that the scope of allyl carbonates was quite
temperature in 4.5 h (entry 2). To our delight, treatment of limited, thus we chose benzyl carbonates as substrates to
benzyl carbonate 1a-2 with the more electrophilic PPh3AuSbF6 examine the reaction scope. As shown in Scheme 2, a wide
complex in THF improved the yield of 2a dramatically to 87% variety of diversely substituted aryl alkynes were suitable for
with a shorter reaction time (entry 4), perhaps due to the this reaction, furnishing the desired naphtho[b]cyclobutenes in
formation of a more stable benzyl cation intermediate during generally good to high yields as single diastereomers. The
the ring-closure process. It is noted that in this case, the electronic nature of the aromatic rings did not have a strong
reaction mixture became viscous as the reaction progressed. influence on this reaction. Both electron-deficient and electron-
It was found that partial polymerization of THF solvent rich substituents on the aryl rings were tolerated well during
occurred under the conditions as evidenced by the NMR spectra the reaction. For example, p-Cl, p-Br, o-Br, p-F, p-CF3 and
of the crude reaction mixture. The reaction could also be p-CO2Et substituted aryl alkynes afforded the corresponding
performed in toluene or CH2Cl2, furnishing 2a in 76% and
58% yields, respectively (entries 5 and 6). A significant counterion
effect on the reactivity was observed, for example, changing the
counterion to NTf2À, OTfÀ or BF4À resulted in lower product yields
(61–79%) and longer reaction time in THF (entries 7–9). Catalyst A
was also found to smoothly catalyze the cycloisomerization of 1a-2
into the desired 2a in toluene (entry 10). Control experiments with
Table 1 Optimization studies for the synthesis of 2a
Entry R1
Catalysta (5 mol%) Solvent Time (h) Yieldb (%) of 2a
c
1
2
3
4
5
6
7
8
Me
Me PPh3AuNTf2
Me PPh3AuCl/AgSbF6 THF
A
Toluene 10
THF 4.5
—
47
18
87
76
58
79
61
69
24
2
3
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
PPh3AuCl/AgSbF6 THF
PPh3AuCl/AgSbF6 Toluene
PPh3AuCl/AgSbF6 CH2Cl2
5
PPh3AuNTf2
PPh3AuCl/AgOTf
PPh3AuCl/AgBF4
A
THF
THF
THF
Toluene
THF
17
18
17
3
14
14
2
9
10
11
12
13
14
15
86
AgSbF6
NRd
NRd
PPh3AuCl
TfOH
THF
CH2Cl2
THF
e
—
Allyl PPh3AuNTf2
10
2
81
84
Allyl PPh3AuCl/ASbF6
THF
a
b
[Au] (5 mol%), [Ag] (5 mol%) for entries 3–6, 8, 9 and 15. Isolated yields.
c
84% of 1a-1 was recovered. d NR = no reaction. e Complex mixture.
Scheme 2 Gold-catalyzed cyclization of bis(propargyl carbonate)s to
naphtho[b]cyclobutenes.a
c
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ion intermediate 10. Subsequent nucleophilic attack of the
Au–C(sp3) bond on the carbonyl moiety of the oxocarbenium
ion gives the same dicarbonate 7 (path b), which is similar to
that of the [2+2] cycloaddition sequence involved in gold-
catalyzed cyclization of 1,7-enyne benzoates.14
In summary, we have discovered a novel gold-catalyzed
cascade cyclization of 1,7-diyn-3,6-bis(propargyl carbonate)s,
which allows the facile synthesis of functionalized naphtho[b]-
cyclobutenes with high stereoselectivity. The reaction likely
proceeds through the generation of bisallenes via gold-catalyzed
double 3,3-rearrangement, followed by cascade cyclization reac-
tions including a decarbonylative cyclization. Bisallenes are well
known to serve as powerful p-components in metal-catalyzed
cyclization reactions.15 The present protocol might be potentially
applied for the efficient generation of bisallenes from non-
benzene-fused propargyl carbonate systems. We are now exploiting
new cascade reactions toward this goal.
Scheme 3 Possible reaction mechanism.
products 2b–2g in 72–85% yields. In the case of 2f (R2 = R3 =
p-CF3C6H4), dicarbonate 3 was also obtained in 12% yield as a
mixture of diastereomers. The structures of 2f and the trans-isomer
of 3 were unambiguously determined by X-ray crystallography.11
p-Me or p-tBu substituted aryl alkynes provided 2h and 2i in good
yields of 82% and 70%, respectively. However, a m-MeO substi-
tuted one gave the desired 2j only in moderate yield of 45%. The
reaction also proceeded well with unsymmetrically substituted
dicarbonates 1k–1m to afford 2k–2m in 55–82% yields. The parent
phenyl rings modified by introducing a methyl group or a fused
benzene ring were also compatible in this cyclization, leading to
the formation of 2n and 2o in 79% and 77% yields, respectively. In
the latter case, catalyst A afforded better results than PPh3AuSbF6.
When substrates 1 bearing two alkyl groups, or one alkyl, one aryl
group on the alkyne terminus were employed, the desired
naphtho[b]cyclobutenes could not be obtained.
We thank the National Natural Science Foundation of China
(Grant Nos. 21121062, 21125210), Chinese Academy of Science,
and the Major State Basic Research Development Program
(Grant No. 2011CB808700) for financial support.
Notes and references
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Based on the above results, a possible reaction mechanism
is depicted in Scheme 3. First, double 3,3-rearrangement reaction
occurs through the nucleophilic attack of the benzyloxycarbonyl
group on the gold(I)-activated alkyne moiety leading to the
formation of the bis(allenyl carbonate) 4. This is followed by
6p-electrocyclic reaction to deliver a 2,3-naphthoquinodimethane
species 5, which can also be represented by the resonance
structure 6, a highly stabilized biradical.12 5/6 undergoes cycliza-
tion spontaneously to provide dicarbonate 7. Then, a gold-assisted
C–O bond cleavage takes place to give a benzylic cation inter-
mediate 8.7 Subsequent ring-closure proceeded by attack of the
benzyloxycarbonyl group from the top side furnishes exclusively
cis-2 (path a). The attack from the bottom side would require
considerable ring strain. The released benzyl cation might induce
a polymerization process of THF.13 It might also be trapped by a
small amount of water since BnOH could be detected in 23%
isolated yield in gold-catalyzed cyclization of 1a-2. We also tried to
11 See ESI†.
trap the 2,3-naphthoquinodimethane intermediate by addition 12 S. Braverman and Y. Duar, J. Am. Chem. Soc., 1990, 112, 5830.
13 For benzyl cation induced polymerization of THF, see: J. W. Kang
and Y.-K. Han, Bull. Korean Chem. Soc., 1997, 18, 433.
14 W. Rao, D. Susanti and P. W. H. Chan, J. Am. Chem. Soc., 2011,
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reaction. Alternatively, intramolecular nucleophilic attack of the
allenic moiety on the gold-activated allene affords oxocarbenium
133, 15248.
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45, 8009; (b) Y.-T. Hong, S.-K. Yoon, S.-K. Kang and C.-M. Yu, Eur. J.
Org. Chem., 2004, 4628; (c) S. M. Kim, J. H. Park, Y. K. Kang and
Y. K. Chung, Angew. Chem., Int. Ed., 2009, 48, 4532.
c
8652 Chem. Commun., 2013, 49, 8650--8652
This journal is The Royal Society of Chemistry 2013