Rh(II)-catalyzed formal [3+3] cycloaddition of diazonaphthoquinones and propargyl alcohols: Synthesis of 2,3-dihydronaphtho-1,4-dioxin derivatives

Article abstract of DOI:10.1016/j.tetlet.2020.151853

A Rh(II)-catalyzed formal [3+3] cyclization of diazonaphthoquinones and propargyl alcohol is reported to afford 2,3-dihydro-1,4-benzodioxins. Various terminal propargyl alcohols react with diazonapthoquinone in the presence of Rh₂(OAc)₄

Full text of DOI:10.1016/j.tetlet.2020.151853

Tetrahedron Letters 61 (2020) 151853
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rh(II)-catalyzed formal [3+3] cycloaddition of diazonaphthoquinones
and propargyl alcohols: Synthesis of 2,3-dihydronaphtho-1,4-dioxin
derivatives
⇑
Mitsuru Kitamura , Tomoaki Nishimura, Kota Otsuka, Hirokazu Shimooka, Tatsuo Okauchi
Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu 804-8550, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A Rh(II)-catalyzed formal [3+3] cyclization of diazonaphthoquinones and propargyl alcohol is reported to
afford 2,3-dihydro-1,4-benzodioxins. Various terminal propargyl alcohols react with diazonaptho-
quinone in the presence of Rh (OAc) to give the corresponding dihydrodioxins in good to high yields.
2 4
However, dihydrodioxins are not formed in the reaction of internal propargyl alcohols, and the O–H
insertion product and 2,5-dihydrofurans are formed as the main product(s) depending on the terminal
substituent. 2,3-Dihydro-1,4-benzodioxins are proposed to be formed via Rh(II)-catalyzed intermolecular
oxonium ylide formation and subsequent 6-exo-dig cyclization with the internal alkynyl group.
Ó 2020 Elsevier Ltd. All rights reserved.
Received 29 February 2020
Revised 13 March 2020
Accepted 16 March 2020
Available online 19 March 2020
Keywords:
Cyclization
Diazo compounds
Diazonaphthoquinone
Propargyl alcohol
Rhodium
Introduction
O–H insertion product 3a when 2-propyn-1-ol was used
(Scheme 2) [9h]. Such formal [3+3] cycloaddition had not been
a
-Diazocarbonyl compounds react with various metal com-
previously reported for the metal-catalyzed reaction of
diazocarbonyl compounds and propargyl alcohol. Only a related
reaction was reported by Katukojvala and co-workers, which
consists of the formation of 1,4-oxazines by the cooperative Rh
(II)/Brønsted acid and Au(I)-catalyzed cyclization of enal
diazocarbonyl compounds and propargylamine via a dienamine
intermediate [10].
We were intrigued by this unexpected formal [3+3] cycloaddi-
tion and anticipated that this transformation could be a new and
simple method for the synthesis of 2,3-dihydronaphtho[1,2-b]-
1,4-dioxin derivatives, which are potentially attractive bioactive
compounds similar to 2,3-dihydro-1,4-benzodioxins [11]. There-
fore, the generality and efficiency of the Rh-catalyzed reaction of
diazonaphthoquinones with propargylic alcohols were explored.
In this letter, we describe these results in detail.
plexes to form metal carbenes, which are widely used as interme-
diates in organic synthesis [1]. One of the useful reactions of metal
carbenes is the insertion reaction into X–H bonds (X = heteroatom)
[
1,2]. In particular, OAH insertion reactions between metal carbe-
nes and alcohols are well studied [3], and the reaction mechanism
is proposed to proceed via formation of an oxonium ylide followed
by a proton transfer reaction [4]. Interestingly, when propargylic
alcohols are used for the reaction with metal carbenes, allenes
are occasionally formed via a tandem oxonium ylide formation fol-
lowed by [2,3]/[3,3]-sigmatropic rearrangement (Scheme 1) [5].
Further cyclization of the formed allenes has been examined for
the synthesis of heterocycles, namely, 2,5-dihydrofurans [6].
Previously, we developed an efficient synthetic method for the
preparation of diazonaphthoquinones via diazo-transfer with 2-
azido-1,3-dimethylimidazolinium salt [7], and we have subse-
quently been investigating a series of metal-catalyzed reactions
using these products [8,9]. In the study of the Rh(II)-catalyzed O–
H insertion reaction of diazonaphthoquinone and alcohols, we
observed the formation of formal [3+3] cycloaddition product 2a
Results and discussion
Initially, the model reaction of diazonaphthoquinone 1a with 2-
propyn-1-ol was examined in the presence of a Rh catalyst at 60 °C
for 16 h (Table 1). When the reaction was carried out with
(
2,3-dihydronaphtho[1,2-b]-1,4-dioxin) along with the expected
2 4
Rh (OAc) (3 mol%) in benzene under several concentrations
⇑
Corresponding author.
E-mail address: kita@che.kyutech.ac.jp (M. Kitamura).
(0.01–0.2 M for 1a) (Entries 1–4), dihydrodioxin 2a was obtained
in the highest yield (94%) at the concentration of 0.1 M (Entry 3).
https://doi.org/10.1016/j.tetlet.2020.151853
040-4039/Ó 2020 Elsevier Ltd. All rights reserved.
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2
M. Kitamura et al. / Tetrahedron Letters 61 (2020) 151853
Table 1
Optimization of the formation of 2a by the Rh-catalyzed reaction of 1a and 2-propyn-
a
1-ol.
Entry
Solvent
Conc. (M)
Rh cat.b
Yield (%)c
Scheme 1. Metal-catalyzed reaction of a-diazocarbonyl compounds and propargyl
alcohol.
2a
3a
4a
1
2
3
4
5
6
7
8
9
1
1
1
1
1
Benzene
Benzene
Benzene
Benzene
0.01
0.05
0.1
0.2
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
2
2
2
2
2
2
2
2
2
2
2
2
2
2
(OAc)
(OAc)
(OAc)
(OAc)
(OAc)
(OAc)
(OAc)
(OAc)
(OAc)
4
4
4
4
4
4
4
4
4
51
81
94
79
0
0
0
0
0
0
0
18
0
5
0
0
0
22
61
1
6
1
15
0
0
0
0
0
0
0
0
0
0
CH
3
CN
THF
0
CH
CH
2
Cl
ClCH
2
41
67
81
76
76
71
0
2
2
Cl
Toluene
Benzene
Benzene
Benzene
Benzene
Benzene
0
1
2
3
4
(oct)
4
(esp)
(TPA)
2
4
(TFA)
(pfb)
4
4
6
a
Reagents and conditions: 1a (0.3 mmol), 2-propyn-1-ol (1.5 mmol), Rh
3 mol%), solvent, 60 °C, 16 h.
2
(OAc)
4
(
b
0
0
oct
=
octanoate, esp
=
a,
a,a
,a -tetramethyl-1,3-benzenedipropionate,
Scheme 2. Unexpected result in the Rh-catalyzed reaction of diazonaphthoquinone
a and propargyl alcohol.
TPA = triphenylacetate. TFA = trifluoro-acetate, pfb = perfluorobutyrate.
1
c
Isolated yield.
Nonpolar solvents were particularly suitable for the reaction
Entries 3 and 5–9), and benzene was determined to give the best
results (Entry 3). In the screening of ligands for the Rh catalyst
Entries 3 and 10–14), Rh (OAc) gave the best result for the forma-
tion of 2a (Entry 3), and O–H insertion product 3a was observed
when the Rh catalyst contained electron-withdrawing ligands such
as trifluoroacetate and perfluorobutyrate (Table 1, Entries 13 and
(
In the reaction of 1-substituted-2-propyn-1-ol derivatives (ter-
minal alkynes) with 1a, dihydrodioxins 2 were formed exclusively.
The yield of 2 decreased when the number of substituents
increased (Entries 1 and 2).
(
2
4
In contrast, dihydrodioxins 2 were not obtained in the reaction
of internal propargyl alcohols (Entries 3–7). Propargyl alcohols
containing methyl, phenyl, or 1-alkynyl groups as the terminal
1
4).
Then, having established the optimized reaction conditions
5 equiv. of propargylic alcohol, 3 mol% Rh (OAc) in benzene
0.1 M for 1) at 60 °C], the scope of the Rh-catalyzed cyclization
3
substituent R reacted with 1a to afford a mixture of O–H insertion
[
(
2
4
product 3 and spirocompounds 4 (Entries 3–5). O–H insertion pro-
duct 3 was formed as the only product in the reaction of 3-
trimethylsilyl-2-propyn-1-ol (Entry 6). When the terminal sub-
reaction of alkynes and diazonaphthoquinones was explored.
First, the reaction between various substituted diazonaphtho-
quinones 1 and 2-propyn-1-ol was examined (Table 2). The
cyclization was strongly affected by the C-3 substituents of the dia-
3
stituent R was a hydroxymethyl group, dihydrodioxines 2 were
formed as a sole product (Entries 7).
To gain insight into the reaction mechanism, several control
experiments were conducted (Scheme 3). First, the three products
2a, 3a, and 4a were treated under the standard reaction conditions
to investigate the occurrence of interconversion or transformation
processes (Eqs. (1)–(3)). Compounds 2a and 4a were not converted
to other forms (Eqs. (1) and (3)). In the case of O–H insertion pro-
duct 3a, formation of 2a and 4a was observed, albeit in low yields
(Eq. (2)). These results suggest that the three products 2, 3, and 4
are not intermediates in the reaction. In the metal-catalyzed for-
mation of 2,5-dihydrofuran derivatives via the reaction of diazo-
1
zonaphthoquinones 1. When the C-3 substituent R was a carbonyl
group, the formal [3+3] cyclization proceeded efficiently (Entries
1
–7). 3-Cyano- and alkoxylmethyl-substituted diazonaphtho-
quinones 1 also cyclized to dihydrodioxin 2 in good yields (Entries
and 9). However, the reaction of unsubstituted or alkyl-substi-
8
tuted diazonaphthoquinones 1 gave 2 in lower yields, and O–H
insertion product 3 and/or oxy-spiro compounds 4 were mainly
formed (Entries 10–12). In addition, the formation of allene 5m
was observed in the reaction of isopropyl-substituted diazonaph-
thoquinone (Entry 12). Interference in the dioxane formation was
not observed upon introducing a methyl group at the C-4 position
or a methoxy group at the C-8 position (Entries 13 and 14).
Next, the effect of substituents at the terminal and internal
positions of the propargylic alcohol was examined (Table 3).
compounds and propargyl alcohol,
a-hydroxy allenes were sug-
gested as intermediates [5,6]. However, we ruled out the formation
of hydroxy allene as intermediate in the reactions leading to cyclic
compounds 2 and 4 because dihydrodioxin 2m and spirocom-
pound 4m were not formed from hydroxy allene 5m (Eq. (4)).

M. Kitamura et al. / Tetrahedron Letters 61 (2020) 151853
3
Table 2
Rh-catalyzed reaction of various diazonaphthoquinones 1 and 2-propyn-1-ol.
a
Entry R1
R2
R3
Time (h) Yield (%)b
1
2
3
4
5
6
7
8
9
1
1
1
1
1
CO
CO
CO
CO
CHO
COMe
COPh
CN
2
2
2
2
Et
Pr
Ph
NHPh
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
18
17
12
24
16
12
14
8
9
6
6
16
12
2b 90
2c 92
2d 76, 3d 5
2e 79
2f 54
Scheme 3. Investigation of the reaction mechanism.
2g 81
2h 82
2i 40, 4i 4
2j 60, 3j 4, 4j 14
2k 17, 3k 33
2l 31, 3l 40, 4l 25
2m 26, 3m 33, 4m 21, 5m 17
2n 87
CH
H
2
OMe
0
1
2
3
4
Me
i
Pr
CO
CO
2
Me
Me
2
OMe 18
2o 78, 3o 6, 4o 7
a
2 4
Reagents and conditions: 1 (0.3 mmol), 2-propyn-1-ol (1.5 mmol), Rh (OAc)
(
3 mol%), benzene (3 mL), 60 °C.
Isolated yield.
b
Table 3
a
Substrate scope for internal propargyl alcohols.
Scheme 4. Possible reaction mechanism.
On the basis of the above results and literature reports, a plau-
sible reaction mechanism for the Rh-catalyzed reaction of propar-
gylic alcohol and diazonaphthoquinones 1a is presented in
Scheme 4. In the first step, the Rh(II) catalyst reacts with 1a to form
rhodium–carbene complex I. Then, the nucleophilic attack of
propargylic alcohol on carbene complex I proceeds to form oxo-
nium ylide II, which may be in equilibrium with Rh naphtholate
III. In path a, dihydrodioxin 2a is formed by oxy rhodation via 6-
exo-dig cyclization. Meanwhile, 3a and 4a are formed from oxo-
nium ylide II via a 1,2 proton shift (path b) and migratory insertion
of the C„C triple bond into the Rh–C bond (5-endo-dig cyclization,
path c), respectively. Since transformation from 3a to 2a occurs in
low yield as shown in Eq. (2), this interconversion would not be a
main pathway for the formation of 2a.
R1
R2
R3
Entry
Time (h)
Yield (%)
1
2
3
4
CH
CH
H
H
H
3
H
CH
H
H
H
H
H
Me
Ph
C„C(CH
TMS
2
CH OH
16
16
17
16
10
16
14
2p 66
2q 31
3r 38, 4r 34
3s 22, 4s 6
3t 21, 4t 23
3
3
b
5
2 3 3
) CH
6
7
H
H
H
H
3u 88
c
2v 58d
a
Reagents and conditions: 1a (0.3 mmol), propargylic alcohol (1.5 mmol), Rh2
OAc)4 (3 mol%), benzene (3 mL), 60 °C.
.2 equiv. of propargylic alcohol was used.
ClCH CH Cl was used as the solvent.
Single geometric isomer. Geometry of the alkene in 2v is not assigned.
(
b
1
c
2
2
d

4
M. Kitamura et al. / Tetrahedron Letters 61 (2020) 151853
Synthesis with Diazo Compounds, John Wiley & Sons, New York, 1998;
Conclusion
(
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2
(OAc)
4
-catalyzed formal [3+3]
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(i) A. Ford, H. Miel, A. Ring, C.N. Slattery, A.R. Maguire, M.A. McKervey, Chem.
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cyclization of diazonaphthoquinones and propargyl alcohol to
afford 2,3-dihydro-1,4-benzodioxins, which are formed via an oxo-
nium ylide and subsequent 6-exo-dig cyclization. In the reaction of
terminal propargyl alcohols, dihydrodioxins are formed in good to
high yields. However, in the reaction of internal propargyl alcohols,
dihydrodioxins 2 were not necessarily formed, and the O–H inser-
tion product and 2,5-dihydrofurans were formed as the main pro-
duct(s) depending on the terminal substituent.
[
[
2] A. Padwa, S.F. Hornbuckle, Chem. Rev. 91 (1991) 3263–3309.
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Declaration of Competing Interest
(2015) 15204–15207.
7] (a) M. Kitamura, N. Tashiro, R. Sakata, T. Okauchi, Synlett (2010) 2503–2505;
(
b) M. Kitamura, R. Sakata, N. Tashiro, A. Ikegami, T. Okauchi, Bull. Chem. Soc.
Jpn. 88 (2015) 824–833.
[8] For a review, see: D.I.A. Othman, M. Kitamura Heterocycles 92 (2016) 1761–
783.
9] (a) For selected examples: M. Kitamura, R. Sakata, T. Okauchi Tetrahedron Lett.
2 (2011) 1931–1933;
(b) M. Kitamura, M. Kisanuki, R. Sakata, T. Okauchi, Chem. Lett. 40 (2011)
129–1131;
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
1
[
5
Acknowledgement
1
(
(
c) M. Kitamura, M. Kisanuki, T. Okauchi, Eur. J. Org. Chem. (2012) 905–907;
d) M. Kitamura, K. Araki, H. Matsuzaki, T. Okauchi, Eur. J. Org. Chem. (2013)
This work was supported by a Grant in Aid for KAKENHI
17K19125).
(
5
(
045–5049;
e) M. Kitamura, K. Kubo, S. Yoshinaga, H. Matsuzaki, K. Ezaki, T. Matsuura, D.
Matsuura, N. Fukuzumi, K. Araki, M. Narasaki, Tetrahedron Lett. 55 (2014)
653–1656;
f) M. Kitamura, M. Kisanuki, K. Kanemura, T. Okauchi, Org. Lett. 16 (2014)
554–1557;
Appendix A. Supplementary data
1
(
1
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2020.151853.
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(
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g) M. Kitamura, S. Takahashi, T. Okauchi, J. Org. Chem. 80 (2015) 8406–8416;
h) M. Kitamura, K. Otsuka, S. Takahashi, T. Okauchi, Tetrahedron Lett. 58
2017) 3508–3511;
i) D.I.A. Othman, K. Otsuka, S. Takahashi, K.B. Selim, M.A. El-Sayed, A.S.
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