Ring-Opening/Expansion Rearrangement of Cycloprop[2,3]inden-1-ols Catalyzed by p-Toluenesulfonic Acid

Article abstract of DOI:10.1002/adsc.201600246

A divergent approach to generate either 1-hydroxymethylindenes (which could then be converted to benzofulvenes through a dehydration reaction) or naphthalenes by the rearrangement of cycloprop[2,3]inden-1-ols is reported. The effect of the cyclopropyl ring substitution pattern on ring-opening/expansion rearrangements of the substrates was systemically studied. (Figure presented.) .

Full text of DOI:10.1002/adsc.201600246

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DOI: 10.1002/adsc.201600246
Ring-Opening/Expansion Rearrangement of Cycloprop[2,3]inden-
1-ols Catalyzed by p-Toluenesulfonic Acid
Pei-Fang Li,a Cheng-Bo Yi,a Shu-Jian Ren,a and Jin Qua,*
a
Key Laboratory and Institute of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry,
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071,
Peopleꢀs Republic of China
E-mail: qujin@nankai.edu.cn
Received: March 3, 2016; Revised: April 1, 2016; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600246.
Abstract: A divergent approach to generate either
1-hydroxymethylindenes (which could then be con-
verted to benzofulvenes through a dehydration re-
action) or naphthalenes by the rearrangement of cy-
cloprop[2,3]inden-1-ols is reported. The effect of
the cyclopropyl ring substitution pattern on ring-
opening/expansion rearrangements of the substrates
was systemically studied.
benzofulvene and naphthalene skeletons and the
dearth of syntheses of these structures via rearrange-
ments of strained rings make additional research in
this area desirable.
˘
According to reports from the Razus¸ group and the
Friedrich group, treatment of substituted endo-cyclo-
prop[2,3]inden-1-ols or their 3,5-dinitrobenzoate
esters in buffered or acidic organic-aqueous solutions
results in the epimerization of the hydroxy groups or
hydrolysis of the esters.[6] Although the primary inter-
est of these researchers was to investigate the possible
antihomoaromaticity of the cycloprop[2,3]inden-1-yl
cation, they observed the formation of small amounts
of naphthalenes. Inspired by these pioneering studies
and owing to our interest in ring-opening rearrange-
Keywords: benzofulvenes; naphthalenes; rearrange-
ment; ring-expansion; ring-opening
Investigation of methods to synthesize benzofulvenes ments of cyclopropyl carbinols,[7] in this study, we syn-
or isomeric naphthalenes is currently an active area thesized a series of substituted cycloprop[2,3]inden-1-
of research owing to the special properties displayed ols and investigated their rearrangements. We found
by compounds with these aromatic core structures in that the rearrangements of cycloprop[2,3]inden-1-ols
the fields of materials science, organometallics, and catalyzed by TsOH·H2O led to 1-hydroxymethylin-
medicinal chemistry.[1,2] Substantial effort has been de- denes (which could then be converted to benzoful-
voted to the construction of these two motifs by venes through a dehydration reaction) or naphtha-
means of cyclization and annulation reactions, as well lenes depending on the substituent at the C-3 position
as transition metal-mediated coupling reactions.[3,4] of the substrate.
Although constructing benzofulvenes or naphthalenes
endo-Cycloprop[2,3]inden-1-ols were prepared by
via rearrangement of strained rings is an unconven- reduction of indenone, Simmons–Smith cyclopropana-
tional strategy, it has been shown to be a valid and tion, oxidation of the hydroxy group, and addition of
sometimes more efficient alternative to standard a nucleophile to the resulting ketone.[8] In previous
methods for preparing these target molecules.[5] For studies, we showed that under refluxing conditions,
example, Huang and Yang reported that the reaction water can act as a mildly acidic catalyst to promote
of alkylidenecyclopropanes with acyl chlorides in the organic reactions traditionally catalyzed by Brønsted
presence of aluminum chloride affords benzofulvene or Lewis acids.[7,9] We found that treatment of cyclo-
derivatives in good to excellent yields.[5c] Liu et al. prop[2,3]inden-1-ol 1a in refluxing water led to epi-
used a novel Eu(OTf)3-catalyzed ring-expansion rear- merization of the C-1 carbon, a result that was in
rangement of trimethylsilyl-substituted cycloprop- agreement with previous experimental results.[6b]
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
arrangement of vinylcyclopropenes to produce either hydroxymethylindene 2a was formed by attack of
naphthalene or indene skeletons, depending on the a water molecule at C-10 (Table 1, entry 1).[10] Sub-
choice of the Lewis acid.[5i] The importance of the strate 1b, in which the substituent at C-2 (the R2
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Table 1. Substituent effects on the reactions of endo-cycloprop[2,3]inden-1-
ols.[a]
[a]
Reaction conditions: substrates (0.5 mmol) were treated with TsOH·H2O
(10 mol%) in 1:1 (v/v) CH3CN/H2O at refluxing temperature. Isolated
yields are given.
group) was changed from a hydrogen atom to
Experimental results obtained in our lab and re-
a methyl group, reacted similarly but required a short- ported in the literature show that under neutral or
er reaction time (entry 2). When the substituent at C- mildly acidic conditions, C-1 of cycloprop[2,3]inden-1-
3 (the R3 group) was changed from a hydrogen atom yl cation A undergoes a hydrolytic reaction that re-
to a methyl group, selectivity for naphthalene forma- sults in the formation of the exo-cycloprop[2,3]inden-
tion was observed; substituted naphthalene 3c was ob- 1-ol products (Scheme 1).[6b] Olah and co-workers
tained in 70% yield, along with only 4% of 1- studied charge delocalization in cycloprop[2,3]inden-l-
hydroxyACHTUNGTRENNUNG
methylindene product 2c (entry 3). Changing y1 cation A by means of 13C NMR[11] and found that
R3 of 1c from a methyl group to a phenyl group re- there was more charge delocalization at C-10 and less
sulted in exclusive formation of the corresponding at C-3 of the cyclopropyl ring caused by the antiho-
substituted naphthalene (3d, entry 4). Substrate 1e moaromatic effect.[6a] These results explain the nucle-
(R3 =Ph, R1 =H) afforded naphthalene 3e, but the re- ophilic attack of water at C-10 and cleavage of the C-
action took longer than the reaction of 1d (entry 5). 2/C-10 bond, as well as the fact that the reactions of
Substrate 1f, in which R4 of 1a was changed from a hy- 1b and 1f were faster than the reaction of 1a when C-
drogen atom to a methyl group, gave 1-hydroxyme- 2 or C-10 was substituted with a methyl group. How-
thylindenes 2f (entry 6) and the rearrangement reac- ever, when R3 was an alkyl or aryl group, cyclopropyl
tion was faster than the reaction of 1a.
ring expansion via cleavage of the C-2/C-3 bond,
Scheme 1. Mechanism for the formation of 1-hydroxymethylindene and naphthalene products.
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Table 2. Synthesis of 1-hydroxymethylindenes via ring-opening rearrangements of endo-cycloprop[2,3]inden-1-ols 1.[a]
[a]
Substrates (0.5 mmol) were treated with TsOH·H2O (10 mol%) in 1:1 (v/v) CH3CN/H2O (10 mL) at refluxing tempera-
ture. Isolated yields are given.
which transforms cation A to benzylic and tertiary and 1,4-asymmetrically substituted biarylnaphthalenes
cation B, becomes more favorable. Deprotonation of (entries 3–8), which are challenging to synthesize via
cation B provides naphthalene products 3.
coupling-based strategies.[4b,c,j,k]
We investigated the generality of this ring-opening
In summary, we have elucidated the effects of sub-
rearrangement by varying the substituent at C- stituents on the cyclopropane ring in the p-toluenesul-
1 (Table 2). Aryl-substituted substrates 1g–1o, which
Table 3. Transformation of 1-hydroxymethylindenes to ben-
have electron-donating or electron-withdrawing
groups at various positions on the aromatic ring,
showed good reactivities and afforded 1-hydroxyme-
thylindenes 2g–2o in good to excellent yields. In addi-
tion, the reaction of propargylic alcohol 1p afforded
ring-opening product 2p in 80% yield. 1-Hydroxyme-
thylindenes 2q–2w, which have substituents at various
positions on the aromatic ring of the indene moiety,
were also obtained in high yields.
zofulvenes.[a]
Entry
Substrate
Product
Yield [%]
The 1-hydroxymethylindenes could be readily
transformed into benzofulvenes by treatment with tri-
fluoroacetic anhydride and triethylamine in dichloro-
methane (Table 3).
We found that ring-expansion rearrangements of C-
3 substituted cycloprop[2,3]inden-1-ols 5 afforded
aryl-substituted naphthalenes 6 in higher yields in tol-
uene than in CH3CN/H2O solution (Table 4, entries 1
and 2). Using this method, we could also obtain 1,3-
1
2
3
4
5
6
2a
2b
2k
2m
2s
4a
4b
4k
4m
4s
92
85
97
92
91
87
2u
4u
[a]
Substrates (0.5 mmol) were treated with (CF3CO)2O
(1.2 equiv.) and Et3N (3.0 equiv.) in CH2Cl2 (5 mL). Iso-
lated yields are given.
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Table 4. Synthesis of substituted naphthalenes via ring-ex-
ature and monitored by TLC. Upon consumption of the
starting material, the resulting solution was diluted with
CH2Cl2. The mixture was washed with water, and then the
aqueous layer was extracted with CH2Cl2. The organic layer
was washed with brine, dried over MgSO4, then concentrat-
ed under vacuum to give the crude product, which was puri-
fied by flash column chromatography (elution: PE) to
afford the desired product 4.
pansion rearrangements of cycloprop[2,3]inden-1-ols.[a]
Entry Substrate R1/R2/R3
Yield of 6 [%]
Acknowledgements
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
H/H/4-OMeC6H4
H/H/4-ClC6H4
H/Ph/Ph
97
99
98
95
92
92
91
We are grateful to the National Natural Science Foundation
of China (21072098, 21372119) and Tianjin Natural Science
Foundation (14JCYBJC20200).
H/t-Bu/Ph
4-MeC6H4/H/Ph
4-CF3C6H4/H/Ph
C4H3S/H/Ph
References
4-MeC6H4/H/4-ClC6H4 98
[a]
Substrates (0.5 mmol) were treated with TsOH·H2O
(10 mol%) in refluxing toluene (5 mL). Isolated yields
are given.
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rearrangements of cycloprop[2,3]inden-1-ols, which
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Experimental Section
General Procedure for the Ring-Opening/Expansion
Rearrangements of endo-Cycloprop[2,3]inden-1-ol
1 or 5
To a round-bottom flask (25 mL) containing cyclopro-
p[2,3]inden-1-ol 1 (0.5 mmol, 1.0 equiv.) was added CH3CN/
H2O (v/v=1:1, 10 mL) (or 5 mL of toluene for 5), and then
to the solution was added p-TsOH·H2O (10 mol%). The
flask was fitted with a condenser, stirred at the indicated
temperature, and monitored by TLC. Upon consumption of
the starting material, the resulting solution was cooled to
room temperature and then a saturated aqueous solution of
NaHCO3 was added to the mixture which was then extract-
ed with EtOAc. The organic layer was washed with brine,
dried over MgSO4, then concentrated under vacuum to give
the crude product, which was purified by flash column chro-
matography (elution: PE:EA=3:1 for 2 or PE for 6) to
afford the desired product 2 or 6.
General Procedure for the Transformation of 1-
Hydroxymethylindenes 2 to Benzofulvenes 4
To a round-bottom flask (10 mL) containing alcohol 2
(0.5 mmol, 1.0 equiv.) was added CH2Cl2 (5.0 mL), and then
to the solution was added trifluoroacetic anhydride
(0.6 mmol, 1.2 equiv.) and Et3N (1.5 mmol, 3.0 equiv.) at
room temperature. The reaction was stirred at room temper-
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6 Ring-Opening/Expansion Rearrangement of
Cycloprop[2,3]inden-1-ols Catalyzed by p-Toluenesulfonic
Acid
Adv. Synth. Catal. 2016, 358, 1 – 6
Pei-Fang Li, Cheng-Bo Yi, Shu-Jian Ren, Jin Qu*
Adv. Synth. Catal. 0000, 000, 0 – 0
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