Synthesis of perinaphthenones through rhodium-catalyzed dehydrative annulation of 1-naphthoic acids with alkynes

Article abstract of DOI:10.1039/c8ob01453a

An efficient approach to the synthesis of perinaphthenones via the rhodium-catalyzed dehydrative annulation of 1-naphthoic acids with internal alkynes was developed. Norbornadiene can act as an acetylene equivalent to give unsubstituted perinaphthenones at the 2- and 3-positions via dehydrative annulation followed by a retro Diels-Alder reaction.

Full text of DOI:10.1039/c8ob01453a

Organic &
Biomolecular Chemistry
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Synthesis of perinaphthenones through rhodium-
catalyzed dehydrative annulation of 1-naphthoic
acids with alkynes†
Cite this: Org. Biomol. Chem., 2018,
6, 7583
1
Received 20th June 2018,
Accepted 4th October 2018
a
a
a
a,b
Takahide Fukuyama, * Taiki Sugimori, Shinji Maetani and Ilhyong Ryu
DOI: 10.1039/c8ob01453a
rsc.li/obc
An efficient approach to the synthesis of perinaphthenones via the
The reaction of 1-naphthoic acid (1a) with 4-octyne (2a) was
rhodium-catalyzed dehydrative annulation of 1-naphthoic acids investigated as a model reaction. When the reaction of 1a with
with internal alkynes was developed. Norbornadiene can act as an 2a (3 equiv.) was carried out in the presence of [RhCl(cod)]
acetylene equivalent to give unsubstituted perinaphthenones at (5 mol%), PPh (10 mol%), KI (50 mol%), and Piv O (3 equiv.)
the 2- and 3-positions via dehydrative annulation followed by a at 160 °C for 20 h, perinaphthenone 3a was obtained in a 52%
2
3
2
retro Diels–Alder reaction.
yield. The reaction also gave naphthalene in 6% yield together
with unreacted 1a (18%) and a mixed anhydride of 1a with
pivalic acid (25%) (Table 1, entry 1). Similar results were
obtained when bis(diphenylphosphino)-methane (DPPM) and
bis(diphenylphosphino)ethane (DPPE) were used as a ligand
Perinaphthenones (also called phenalenones) and their deriva-
tives have attracted intense attention because of their unique
1
physical and biological properties. Their structures can be
1
2
found in widely used O
2
photosensitizers. Perinaphthenone
(
entries 2 and 4). In the absence of KI, the reaction became
derivatives also exhibit diverse biological qualities that make
quite sluggish (entry 3), which would suggest that the in situ
3
4
5
6
them antifungal, anticancer, antioxidant, anti-HIV, and
13
ligand exchange on rhodium between Cl and I was effective.
7
anti-malarial. Therefore, the development of a straightforward
The use of bis(diphenylphosphino)propane (DPPP) and bis
method using readily available substrates to construct peri-
(diphenylphosphino)butane (DPPB) gave lower yields of 3a
8
naphthenone skeletons is highly desired.
The use of carboxylic acids as a carbon resource for tran-
sition-metal-catalyzed reactions has been a steadily growing
9
–12
area of research for the past few decades.
We recently
1
3
reported the rhodium-catalyzed synthesis of dibenzofurans
1
4
and fluorenones via decarbonylative C–H arylation of 2-aryl-
oxybenzoic acids and C–H acylation of 2-arylbenzoic acids,
respectively (Scheme 1, eqn (1) and (2)). As suggested, we used
acylrhodium species to form the key intermediates for these
two reactions. We envisaged that intermolecular trapping of
the acylrhodium species derived from 1-naphtohoic acids by
1
5
16
alkynes followed by C–H activation at a peri-position would
lead to the formation of perinaphthenones (Scheme 1, eqn
(
3)). Herein we report the Rh-catalyzed dehydrative annula-
1
7
tion of 1-naphthoic acids with alkynes, which led to a novel
synthesis of perinaphthenones.
a
Department of Chemistry, Graduate School of Science, Osaka Prefecture University,
Sakai, Osaka 599-8531, Japan. E-mail: fukuyama@c.s.osakafu-u.ac.jp
b
Department of Applied Chemistry, National Chiao Tung University, Hsinchu,
Taiwan
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
Scheme 1 Rh-Catalyzed cyclization reactions of aromatic carboxylic
c8ob01453a
acids.
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a
Table 1 Reaction of 1-naphthoic acid 1a with 4-octyne 2a
Table 2 Rh-Catalyzed dehydrative annulation of 1a with alkynes 2
leading to perinaphtenones
a
b
Entry
Ligand (mol%)
PPh (10)
DPPM (5)
DPPM (5)
DPPE (5)
DPPP (5)
DPPB (5)
DPPM (5)
DPPM (5)
Solvent
Time (h)
Yield (%)
b
Entry
1
2
3
Yield (%)
1
2
3
4
5
6
7
8
3
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Dioxane
Dioxane
20
20
20
20
20
20
20
30
52
54
15
88
c
50
38
18
79
94(88)
2
3
77
a
Conditions: 1a (0.5 mmol), 2a (1.5 mmol), [RhCl(cod)]
2
(2.5 mol%),
2
cod = 1,4-cyclooctadiene, ligand (5 or 10 mol%), KI (0.25 mmol), Piv O
b
(
1.5 mmol), solvent (0.5 mL), 160 °C. Yield was determined by
H-NMR analysis using Cl CHCHCl as an internal standard. The iso-
1
2 2
c
c
94(45 : 55)
lated yield appears in parenthesis. The reaction was carried out
without KI.
(
entries 5 and 6). Consequently, we were pleased when the use
c
4
85(47 : 53)
of 1,4-dioxane as a solvent in place of toluene dramatically
increased the yield of 3a (79%, entry 7). Then, an extended
reaction time of 30 h improved the isolated yield of 3a to 88%
(entry 8).
Having the optimized conditions (DPPM, dioxane, 30 h) in
hand, we then examined the scope of the present perinaphthe-
none synthesis (Table 2). The reaction of 1a with 3-hexyne (2b)
gave diethyl-substituted perinaphthenone 3b in 77% yield
c
5
6
75(44 : 56)
(Table 2, entry 2). Unsymmetrical dialkylalkynes, such as
2
-hexyne (2c) and 3-octyne (2d), gave the corresponding peri-
naphthenones as a mixture of regioisomers in 94 and 85%
yields, respectively (Table 2, entries 3 and 4). The reaction of
44%
1
a with 1-phenylpentyne 2g gave a 44 : 56 mixture of 3e and 3e′
in 75% yield (Table 2, entry 5). In contrast to these three
examples, the reaction of 1a with 1-trimethylsilylpentyne (2f)
gave 3f selectively, albeit in a modest yield (Table 2, entry 6).
The reaction of 1a with diarylacetylenes, such as diphenyl-
acetylene (2g) and di-para-tolylacetylene (2h), was sluggish in
giving the corresponding perinaphthenones 3g and 3h in
yields of 49 and 21%, respectively. A prolonged reaction time
of 96 h improved the yields of 3g and 3h to 63 and 49%,
respectively (Table 2, entries 7 and 8).
We next investigated the reaction of substituted naphthoic
acids 1b–e and quinoline carboxylic acid 1f with 4-octyne (2a),
and the results are summarized in Table 3. When the reaction
of 4-methyl-1-naphthoic acid (1b) with 2a was carried out crude reaction mixture. 40 h. 96 h.
under standard conditions (160 °C, 30 h), a 64/36 mixture of 3i
d
e
e
7
8
49 (63)
d
21 (49)
a
1 (0.5 mmol), 2 (1.5 mmol), [RhCl(cod)]2 (2.5 mol%), cod = 1,4-
O (1.5 mmol),
dioxane (1 mL), 160 °C, 30 h. Isolated yield after chromatography on
cyclooctadiene, DPPM (5 mol%), KI (0.25 mmol), Piv
2
b
c
1
SiO . The product ratio was determined by H-NMR analysis of the
2
d e
and 3i′ with carbonyl migration was obtained (Table 3,
entry 1). In a similar manner, the reaction of 4-furuoro- and ture (180 °C) (entries 2, 4 and 6). Interestingly, the reaction of
4
-methoxy-1-naphthoic acid (1c and 1d) gave a mixture of pro- ortho-ethoxynaphthoic acid 1e gave carbonyl-migrated product
ducts in similar ratios (Table 3, entries 3 and 5). In these 3l′ selectively (entry 7). In this case, steric repulsion between
cases, the formation of the migrated products was effectively the ortho-substituent and a carbonyl group would accelerate
suppressed at <8% by simply employing an elevated tempera- the formation of an arylrhodium complex from an acylrho-
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a
Table 3 Rh-Catalyzed dehydrative annulation of substituted naphthoic acids 1 with alkynes 2
b
Entry
1
2
3
Yield (%)
86(64 : 36)
82(93 : 7)
c
2
3
4
79(66 : 34)
77(92 : 8)
c
5
6
85(67 : 33)
87(92 : 8)
c
7
54(0 : 100)
54(94 : 6)
d
8
a
1
(0.5 mmol), 2 (1.5 mmol), [RhCl(cod)]
2
(2.5 mol%), cod = 1,4-cyclooctadiene, DPPM (5 mol%), KI (0.25 mmol), Piv
2
O (1.5 mmol), dioxane
b
1
(1 mL), 160 °C, 30 h. Isolated yield after chromatography on SiO . The product ratio was determined by H-NMR analysis of the crude reaction
2
c d
mixture. 180 °C. Dioxane (3 mL).
dium complex (vide infra). Quinoline carboxylic acid reacted is outlined in Scheme 3. The oxidative addition of the acyl–O
with 2a to give 3k in good selectivity even at 160 °C (entry 8). bond of the in situ-formed mixed anhydride 1b′ into the
Since the use of acetylene gas is somewhat tedious, we then rhodium(I) catalyst would give acylrhodium species A, which
tested a theory for a synthetically equivalent reaction of 1a would then undergo C–H cleavage via a concerted metalation/
1
9
with norbornadiene (2i), wherein the annulation product deprotonation (CMD) process to give the rhodacycle B.
would undergo subsequent retro-Diels–Alder reaction Insertion of 2a into the rhodium–aryl bond followed by reduc-
Scheme 2). As expected, non-substituted perinaphthenone 3n tive elimination would give the perinaphthenone 3i and regen-
a
(
1
8
was obtained in a 47% yield.
erate the key rhodium(I) species. This catalytic reaction system
A possible reaction mechanism for the formation of peri- includes the decarbonylation of acylrodium species A to give
2
0
naphthenones uses the reaction of 1b with 2a as a model and arylrhodium species D. Insertion of 2a into the rhodium–aryl
bond of D would give vinylrhodium species E. The CMD
process would then give six-membered rhodacycle F.
2
1
Reinsertion of CO followed by reductive elimination gives 3i′.
We speculate that higher temperature would promote the cycli-
zation of A to B and lead to the selective formation of 3i.
A comparison with work from the Miura group is insightful.
They previously reported that the dehydrogenative annulation
of 1-naphthoic acid with diphenyl acetylene in the presence of
a catalytic amount of [Cp*RhCl2]2 and a stoichiometric
2
amount of Cu(OAc) gave naphthopyranones. In that process,
2
2
cyclization took place at an ortho C–H bond. With the
Scheme 2 The use of norbornadiene (2i) as an acetylene equivalent.
present reaction system, however, naphthopyranones were not
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