Rhodium-catalyzed cyclization of acceptor-substituted biphenyl α-diazoketones: A study of the substitution effect on chemoselectivity

Article abstract of DOI:10.1039/c8ob01489b

A range of biphenyl α-diazoketones containing various electron-withdrawing groups (EWG = COCH₃, CN, CO₂Et, COPh, SO₂CH₃, SO₂Ph) on diazo carbon has been investigated for rhodium(ii)-catalyzed intramol

Full text of DOI:10.1039/c8ob01489b

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Rhodium-Catalyzed Cyclization of Acceptor-Substituted Biphenyl
α-Diazoketones: A Study of Substitution Effect on
Chemoselectivity†
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Kuo-Hsin Chen, Yi-Jung Chiang and Jia-Liang Zhu*
www.rsc.org/
A range of biphenyl α-diazoketones containing various electron-withdrawing groups (EWG = COCH
3 2
, CN, CO Et, COPh,
SO CH , SO Ph) on diazo carbon has been investigated for the rhodium(II)-catalyzed intramolecular cyclization. Among
2
3
2
which, the α-acetyl, carboxylate and cyano substituted substrates show markedly different selectivity between aromatic
substitution and aromatic cycloaddition processes, to afford phenanthrol and/or benz[α]azulenone products in varying
ratios. The selectivity is mainly directed by α-substitutions, and also possibly influenced by the substituents on the
biphenyl ring. Moreover, high chemoselectivity for aromatic substitution over cycloaddition is observed for the α-benzoyl
and sulfonyl substituted substrates. But in addition to phenanthrols, these reactions produce aromatic ketone and/or 1,2-
diketones as unprecedented products obtained from diazo precursors. Mechanistic rationales are given in the report.
Introduction
Transition-metal-catalyzed intramolecular cyclization reactions
of aryl α-diazocarbonyl compounds are widely employed for
1
the construction of unsaturated polycycles. Such reactions
typically proceed in either an aromatic cycloaddition (the
2
3
Büchner reaction) or an aromatic substitution pathway,
depending on the pattern of carbenoids to react with aryl
components (Scheme 1). The norcaradiene products
generated by aromatic cycloaddition occasionally undergo a
spontaneous ring expansion to give cycloheptatriene
1
,2b,c
isomers.
Moreover, the aromatic substitution, sometimes Scheme 1 Transition-metal-catalyzed aromatic cycloaddition and aromatic substitution
2
2
also referred as sp C-H insertion, has been proved to involve a
(
sp C-H insertion).
zwitterionic intermediate resulting from electrophilic addition,
3
and therefore differs mechanistically from aliphatic C(sp )-H
substrates may dramatically affect the distribution of products.
In this context, the substituent on diazo carbon (X, Scheme 1)
is considered as key structural component in directing the
4
insertion process. These reactions are traditionally conducted
1
with rhodium(II) or copper catalysts, while in recent years,
5
6
1
0
Rh(III) or some other transition metals have become more
widespread as substitutes for the catalysis.
chemo- and/or regioselectivity. For electronic reasons, it is
believed that α-substituents with different electron-
withdrawing (or donating) abilities can profoundly influence
the electrophilicity of metal carbenes, the most important
However, when the aforementioned two processes are
potentially competitive with each other, chemoselectivity issue
arises. According to literature reports, high selectivity for the
desired reaction pathway can be possibly achieved with a
given diazo substrate, by selecting appropriate dirhodium(II)
7
a,10c
factor
steric features related to an α-substituent, such as the size,
determining the selectivity. Additionally, some
1
0a
11c
geometry and/or conformation,
11a,b
may also need to be
2
b,7
6a,8
9
ligand, catalytic metal or even solvent. Besides, earlier
studies in this area have revealed that a subtle change in diazo
taken into account when evaluating its influence on the
selectivity. So far, the α-substitution strategy has been used in
a few reported studies for controlling the chemoselectivity of
1
2
the processes in Scheme 1. Under same catalytic conditions,
these protocols allow the deliberate generation of different
Department of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan,
R.O.C.
kinds
of
products
(e.g.,
Email: jlzhu@gms.ndhu.edu.tw
†
12a
Electronic Supplementary Informaꢀon (ESI) available: Experimental and spectral
data, x-ray crystallographic structures (CCDC 1813583 and CCDC 1836777) see:
DOI: 10.1039/x0xx00000x
cycloheptapyrrolones/isoquinolinones ) from similar diazo
substrates by simply varying their α-substitutions.
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Scheme
2 Concept of selective generation of phenanthrol or benz[α]azulenone
derivatives.
2
Scheme 3 Preparation of substrates 3a-c. a) PhMgBr, MnCl , LiCl, THF, -10 °C. b)
To further explore the utility of such intriguing substitution- (EtO) CO, NaH, toluene, reflux. c) LiHMDS, CH COCl, toluene, 0 °C. d) LiHMDS, PhCOCl,
2
3
controlled strategy, we initiated
a
program aimed at toluene, 0 °C. e) p-ABSA, Et
3 3
N, CH CN, rt.
investigating the transition metal-catalyzed cyclization of
biphenyl α-diazoketones. Through the variation of substituents
The reactivity of 3a
(OAc) , Rh (oct)
could selectively undergo either aromatic substitution or which were demonstrated to favor either aromatic
-
c
was subsequently examined by using
on diazo carbon, we anticipated to find the candidate(s) that Rh
2
4
2
4
or Rh (esp) as the catalysts (1 mol%),
2
2
3
a
2a
cyclopropanation reaction (Scheme 2). Endowed with the in- substitution or aromatic cycloaddition in many documented
situ enolization, the former process would lead to the cases. With Rh (OAc) or Rh (oct) in CH Cl , the reactions of
assembly of 9-phenanthrol scaffold, a structural motif that 3a exhibited no selective bias between the two competing
2
4
2
4
2
2
1
3
presents in a large number of natural products. It also serves processes, delivering phenanthrol 4a and benz[α]azulenone 5a
as an important pharmacophore in the drug discovery in almost equal amounts (Table 1, entries 1 and 2). Although
1
4
15
process, as well as a useful synthon in coordination and use of Rh
2
(esp)
Accordingly, the development of substitution, significant amount of 5a was still formed (entry 3).
methods for its construction has attracted considerable Unlike 3a, substrate 3b displayed a strong propensity to
2
improved the selectivity for the aromatic
1
6
material chemistry.
1
7
attention in the synthetic community, with many recent undergo aromatic substitution upon exposure to Rh
2
(OAc)
in good yield
other hand, the cycloaddition reaction was supposed to with no trace of cycloaddition product (entries 4 and 5). Only
provide benz[α]azulenones after the ring-opening of the when using Rh (esp) did we isolate the cycloaddition product
cyclopropanes. This type of compounds and their derivatives 5b in detectable quantity (entry 6; 4b: 40%, 5b: 18%). Taken
4
or
1
7c-e,g-I
17g
works highlighting transition-metal catalysis.
2 4
On the Rh (oct) , to afford 10-acyl-9-phenanthrol (4b)
2
2
1
8
have also found wide applications in many fields, especially together, these findings suggest that the α-acetyl group should
1
8b,c,f,g
in optoelectronic science
and physical organic be more effective in inducing aromatic substation than the
1
8h
chemistry. In our studies, a range of electron-withdrawing carboxylate group. Furthermore, high chemoselectivity for
1
9
groups was introduced to the α-carbon (Scheme 2, X), and substitution over cycloaddition was observed for benzoyl-
the resulting acceptor/acceptor (A/A)-substituted diazo substituted precursor 3c. Surprisingly, in addition to offering
compounds indeed showed divergent chemoselectivity upon phenanthrol 4c, the reactions also produced large amounts of
exposure to rhodium catalysts. On this basis, the influence of 2-(biphenyl-2-yl)-1-phenyl-ethan-1-one
(
6
)
and 1-([1,1’-
) (entries 7-9). The
6 were in agreement with those
the substitutions on the biphenyl ring (Y) was also briefly biphenyl]2-yl)-2-phenylethane-1,2-dione (
7
examined. Herein, we wish to disclose the results from these NMR spectroscopic date of
2
1
investigations.
reported in the literature, and the structure of
confirmed by X-ray crystallographic analysis Notably, both
products were formed by losing one carbon unit from 3c
7 was
.
.
Results and discussion
Regarding the stronger electron-withdrawing ability of the
benzoyl group, we originally expected that the carbenoid of 3c
1
Reactivity of the substrates containing carbonyl-related groups
Our initial efforts focused on studying the effect of the
2a,11c
would be more reactive for a nucleophilic addition
than
the one derived from 3b. However, the uniformly lower yields
of 4c than 4b, combined with the formation of 6/7, apparently
do not accommodate this expectation. We therefore propose
that these results are possibly attributed to a steric hindrance
caused by the bulky benzoyl group, which can impede the
access of the phenyl ring to the carbene center. Under such
circumstance, the carbenoid may alternatively undergo a Wolff
carbonyl-related -CO Et, -COCH3 and –COPh groups. The
2
parent substrates 3a
-c were easily prepared in three steps
from 2-chloroacetophenone by cross coupling with the
2
0
Grignard reagent, base-induced esterification or acylation,
and diazo transfer reaction (Scheme 3). In the current
investigation, this sequence allows facile access to a variety of
arene substitution pattern from commercially available
starting material and organomagnesium reagents.
22
23
rearrangement or an O-H insertion reaction (Scheme 4).
The ketene intermediate resulting from the former process
2
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Table 1 Screening for reactivity of 3a-c under rhodium(II) catalysis
a)
b)
b)
Entry
Substrate
Catalyst
4 (yield %)
5 (yield %)
1
2
3
4
5
6
3a
3a
3a
3b
3b
3b
3c
3c
3c
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
2
(OAc)
(oct)
(esp)
(OAc)
(oct)
4
4a (X= CO Et) (35%)
2
2
5a (X = CO Et) (31%)
2
4
4a (47%)
4a (39%)
5a (41%)
2
2
5a (24%)
2
4
4b (X= COCH
3
) (74%)
-
-
2
4
4b (74%)
4b (40%)
2
(esp)
2
3
5b (X= COCH ) (18%)
c)
7
2
(OAc)
4
4c (X= COPh) (26%)
4c (11%)
-
-
-
d)
8
2
(oct)
4
e)
9
2
(esp)
2
4c (10%)
a)
b)
c)
d)
e)
Conducted in a 0.01 M solution of 3. Isolated yield. Yield of 6: 35%; yield of 7: 33%. Yield of 6: 38%; yield of 7: 36%. Yield of 6: 25%; yield of 7: 24%.
can be converted into a β-keto acid via hydrolysis, and methyl, p-fluoro or p-methoxy group with catalytic Rh
subsequent decarboxylation leads to the formation of also produced a mixture of two functional isomers (4d
compound . On the other hand, the hydroxylketone product 4e 5e or 4f 5f). But unlike 3a offering the low chemoselectivity,
generated by the O-H insertion may further undergo a 1,2- all of these substrates demonstrated the preference for
rearrangement with the 2-phenylbenzoyl group, yielding a cycloaddition, in particular of 3f. As compared with 3d
formyl intermediate. In the presence of rhodium catalyst, this acetyl substrates 3g and 3h with the same aryl substituents
intermediate then participates in tandem oxidative only afforded phenanthrols 4g and 4h after chromatographic
produce the purification. In these cases, no benz[α]azulenones or
. To our knowledge, the formation cyclopropanes were detected in the crude reaction mixtures
2
(oct)
4
/
5d
,
6
/
/
/e,
a
2
4
insertion/elimination
sequence,
to
2
a
decarbonylation product
7
of
biologically and synthetically important aromatic 1,2- competing dimerization process. Besides, the aromatic
diketones from diazo compounds. Currently, detailed substitution of m-Me and m-Cl substituted acetyl substrates
mechanistic investigation is under our active pursuit. 3j also proceeded smoothly to give products 4j . For both
Having established the reactivity of 3a and 3b, we also briefly substrates, the reactions occurred regioselectively at the less
examined the effect of the substitution on the phenyl ring hindered site of the phenyl ring, and Rh (OAc) was shown to
intercepted by the carbene species. Thus, a few analogues be more efficient than Rh (oct) in giving better yields of the
bearing electron-withdrawing or donating groups at the meta- products. As such, it can be seen that a weak electron-
or para-position were similarly prepared as 3a (Scheme 5) donating or withdrawing group at the meta or para position
and evaluated under the same catalytic conditions [Rh (OAc) does not exert a significant influence on the chemoselectivity
or Rh (oct) /CH Cl ] (Scheme 6). Similar to what observed for regulated by the α-acetyl substituent. Nevertheless,
7 represents an unprecedented example of producing and the modest yields of the products were probably due to
2
5
26
a
/
k
/k
2
4
2
4
/
b
2
4
2
4
2
2
3a, treatment of carboxylate substrate 3d-f containing p- introducing a strong electron-donating methoxy group in the
O
Ph
O
O
O
Ph
C
Ph
O
H
O
Ph
OH
Wolff
rearrangement
Ph
2
H O
- CO
2
C
O
O
-
2
Rh Ln
O
O
6
Rh
2
L
n
Ph
3
c
Rh(II)
H
Rh
2
L
n
O
O
O
O
-
N
2
Ph
Ph
HO
HO
O
Ph
H
H
2
H O
O-H insertion
O
1,2-rearrangement
Rh(II)
O
O
O
- Rh
2 n
L
2 n
Rh L
O
O
Ph
HO
O
Ph
O
Rh(III)
H
oxidative insertion
elimintion
Rh(II), - CO, - H
-
2
7
Scheme 4 Proposed mechanisms for the formation of 6 and 7.
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2 2 3 3 3
Scheme 5 Preparation of substrates 3d-l. a) ArMgX, MnCl , LiCl, THF, -10 °C. b) (EtO) CO, NaH, toluene, reflux. c) LiHMDS, CH COCl, toluene, 0 °C. d) p-ABSA, Et N, CH CN, rt.
para-position drastically affected the chemoselectivity, with intermediates 1a
the reaction of 3i now favouring cycloaddition to yield diazo transfer reaction (Scheme 7). Under the catalysis of
benz[α]azulenone 5i. We attribute this dichotomy in the Rh (oct) , the parent and para-substituted substrates 3m
-g via based-induced cyanation followed by
-p
2
4
reactivity to an enormously increased electron density at the were found to cleanly undergo cycloaddition to produce
C-1’ position, which can promote the nucleophilic addition of benz[α]azulenones 5m in high to quantitative yields. In
-
p
the C-1’ carbon to the electron-deficient carbenoid. Despite of contrast, substrates 3q-s with the m-substituents tended to
this, we found that aromatic substitution could be renewed favour aromatic substitution, affording the phenanthrols
with the concomitant incorporation of the oxygen atoms into either exclusively (4q
the 3’, 4’-positions, as showcased by the exclusive generation (Scheme 8). Besides, TLC analysis of the reactions of 3q
of 4l from 3l together with the non-conversion of 5r to 4r, suggest that
/4q’, 4s) or as the major products (4r)
-s,
.
these phenanthrol products were derived from the aromatic
substitution rather than the in-situ aromatisation of
corresponding benz[α]azulenone intermediates.
Reactivity of the α-cyano substituted substrates
We further evaluated the cyclization of α-cyano biphenyl
diazoketones 3m
-s,
which were synthesized from
Scheme 6 Rhodium-catalyzed cyclization reactions of substrates 3d-l.
4
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Fig. 1 a) Nitrile and carbenoid are coplanar/the planes of phenyl ring and carbenoid are
parallel. b) Planes of phenyl ring and carbenoid are non-parallel.
deviation can presumably weaken the orbital interaction
Scheme 7 Preparation of 3m-s. a) LDA, p-TsCN, THF, -78 °C to rt. b) p-ABSA, NaH, THF, 0 required for the cycloaddition, and consequently impel the
°
C.
carbenoids to engage in the aromatic substitution.
11c
Previous studies by Charetter et al. have led to the
proposal that the Rh-carbenoids derived from α-diazonitriles
inherently adopt a coplanar conformation with the linear
nitrile group lying in the plane of carbene π-bond. As
compared with the out-of-plane conformation proposed for
other A-A substituted carbenoids (e.g., ester or ketone
carbenoids), the unique steric feature of nitrile carbenoids is
considered to be particularly suited for the cycloaddition
Reactivity of the α-sulfonyl substituted substrates
Finally, we sought to investigate the effect of α-sulfonyl moiety
on the chemoselectivity. To the end, the mesyl and tosyl
substrates 3t and 3u were respectively prepared from ethyl
2
8
biphenyl-2-carboxylate and 1a in
a two-step sequence
(Scheme 9). Treatment of 3t with 1 mol% of Rh (OAc) or
2
4
1
1c
Rh
(oct) in CH Cl for 24 hours only produced 20% of
2 4 2 2
owing to the increased electrophilicity through in-plane
conjugation, and the minimized non-bonding interactions with
phenanthrol 4t. To our surprise, the reactions also gave
2
9
2
7
2a
phenanthrene-9,10-dione (
8)
along with large amounts of
alkenes /arenes in the transition state. Regarding the
biphenyl ketone system, these steric and electronic factors
recovered 3t after chromatographic purification (Scheme 10, a
and b). When proceeding, the color of the reaction mixtures
was found to change from green to yellow in a period of 10
hours, implying a possible decomposition of the catalysts. In
this respect, we further conducted a reaction by increasing the
amount of Rh (oct) (5, 15, 20, 25 mol%), and discovered that a
may explain the strong propensity of substrates 3l-o to
undergo aromatic cycloaddition. In the transition structure,
the requisite p-orbital interaction can occur efficiently
between the parallel phenyl ring and Rh=C bond, with or
without the presence of p-substitution (Fig. 1, a). However,
when a substitutent is introduced in the meta-position, its
steric repulsion with the carbenoid unit may force the two
planes to deviate from the parallel orientation (b). Such
2
4
full consumption of 3t could be attended when the loading
was raised up to 25 mol% (c). Similarly, the reaction of 3u with
Rh (oct) (5 mol%) also gave the formation of compound 8,
2
4
phenanthrol 4u and the recovered starting material (d). After
screening a few catalytic systems, we found that the yields of
OH
O
CN
CN
4t
/
u
could be improved to 60% and 56%, respectively, by
/AgSbF
e). Notably, there is no precedence of producing 10-sulfonyl-
Rh2(oct)4 (1 mol%)
CH2Cl2, rt
and/or
employing a Rh(III)-catalyzed protocol [(Cp*RhCl
2
)
2
]
6
3
l-r
30
Y
(
Y
4
5
phenanthren-9-ol compounds in literature, and the structure
O
O
O
O
of 4t has been unambiguously confirmed by the x-ray crystal
CN
CN
CN
CN
diffraction. Furthermore, we speculated that compound
might be derived from 4t at the expense of rhodium
catalysts, and this assumption has been validated by the
8
/u
CH3
F
OCH3
m (91%)a)
5p (quant.)
5
5n (89%)
5o (97%)
OH
conversion of 4t into
8 under the Rh (oct) -mediated reaction
2 4
OH
OH
conditions (f).
O
CN
CN
CN
CN
+
CH3
+
Cl
Cl
CH3
q (64%)
4
4q' (23%)
4r (56%)
5r (44%)
OH
CN
O
O
4
s (97%)
[
a]
.
Same yield was obtained with Rh2(OAc)4 .
Scheme 9 Preparation of 3t and 3u. a) n-BuLi, (Me)
, MeOH, rt. c) K CO , p-ABSA, CH CN, rt.
2 2 2
SO , THF, 0 °C to rt. b) TsNa 4H O,
Scheme 8 Rh
2
(oct)
4
-catalyzed cyclization of the cyano-substituted substrates 3m-s.
I
2
2
3
3
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favor of the cycloaddition products. For the α-cyano series, the
non- or para-substituted substrates show a strong preference
for aromatic cycloaddition, while the meta-substituted
analogues instead favour aromatic substitution. Predictably,
these established patterns should provide the guidelines for
the selective generation of important phenanthrol or
benz[α]azulenone derivatives with extended functional
diversity. Furthermore, high chemoselectivity for aromatic
substitution over cycloaddition is observed for the benzyl and
sulfonyl substituted substrates. Interestingly, these reactions
Scheme 10 Rhodium-catalyzed reactions of 3t/u and conversion of 4t into 8. a)
Rh
mol%), CH
CH Cl , 40 h, rt; 4t: 40%; 8: 6%; recovered 3t: 0%. d) Rh
u: 11%; 8: 17%; recovered 3u: 15%. e) (Cp*RhCl (2.5 mol%), AgSbF
dichloroethane, reflux, 5 h; 4t: 60%; 4u: 56%. f) Rh (oct) (50 mol%), CH
1%.
2
(OAc)
4
(1 mol%), CH
Cl , 24 h, rt; 4t: 20%; 8: 16%; recovered 3t: 52%. c) Rh
(oct) (5 mol%), CH
(2 equiv.), 1,2-
Cl , rt, 25 h,
2
Cl
2
, 24 h, rt; 4t: 20%; 8: 5%; recovered 3t: 37%. b) Rh
(oct) (25 mol%),
Cl
2 4
(oct) (1
2
2
2
4
2
2
2
4
2
2
, 24 h, rt; not only give phenanthrols but also produce
6-8, with
4
2
)
2
6
compounds 7/8 (or analogues) having never been reported for
2
4
2
2
diazo precursors. The latter findings have offered an
opportunity for developing new synthetic strategies to prepare
useful aromatic 1,2-diketone derivatives.
4
Experimental Section
General
The reagents and catalysts were purchased from commercial
suppliers and used without further purification. Some solvents
2 2 2
were properly dried (THF/Na, toluene and CH Cl /CaH ) and
freshly distilled before each use, while others were directly
used as HPLC grade without pre-treatment (acetonitrile, 1,2-
dichloroethane and methanol). The reactions were monitored
by TLC on 0.25 mm silica plates (60F-254) and visualized by UV
Scheme 11 Plausible mechanism for the generation of 8.
light, ethanolic solution of vanillin (5%) or aqueous KMnO
4
solution (10%). The chromatographic purifications were
1
performed with silica gel (70-230 mesh). The NMR spectra ( H,
A mechanism for producing
8 is tentatively proposed in
Scheme 11. Once 4t or 4u is formed, the sulfonyl oxygen atom
1
3
19
C and F) were recorded on 400 or 300 MHz spectrometer
may coordinate with the rhodium catalyst, to thus trigger a
3
1
using chloroform-d, methanol-d4 or dimethyl sulfoxide-d6 as
1
solvents. The H NMR data are reported as the chemical shift
migration of the electrons and produce a keto sulfonyl
complex. Through the attack by H O at the double bond, this
complex can be decomposed into hydroxysulfone
2
in parts per million, multiplicity (s, singlet; d, doublet; t, triplet;
q, quartet; m, multiplet), coupling constants (J) in Hertz, and
number of protons. The resonances of infrared (IR) spectra are
a
intermediate with losing Rh(II) ion. Subsequently, desulfination
of the intermediate via a proton transfer process results in the
-1
reported in wave numbers (cm ). High resolution mass
spectrometry (HRMS) was determined in electron-impact
ionization (EI) or electrospray ionization (ESI) mode with a
magnetic sector analyzer. The melting points were measured
formation of
that the rhodium species released from this sequence is less
active as the initially introduced Rh (oct) or Rh (oct)
accounting for the incomplete consumption of 3t in some
8. In term of the catalytic activity, we postulate
2
4
2
4
,
/
u
with
a
capillary apparatus and uncorrected. Crystal
and 4t have been
cases (Scheme 10, a, b and d). Since the conversion of a β-
sulfonyl enol fragment into a 1,2-diketone moiety has not yet
been known in literature, a thorough investigation is being
undertaken in order to gain a full understanding of this newly
discovered process.
crystallographic data of compounds
7
deposited in the Cambridge Crystallographic Data Center with
the deposition numbers as CCDC 1813583 and CCDC 1836777.
General Procedure for Rh(II)-Catalyzed Cyclization of Diazo
Precursors
A dry round-bottom flask containing biphenyl α-diazoketone
(1.00 equiv.) and equipped with a stir bar was flushed with N2,
followed by charging with CH Cl (0.01 M of ) and the
rhodium(II) catalyst (0.01 equiv.). Under a N atmosphere, the
3
Conclusions
2
2
3
In the biphenyl α-diazoketone system, the substitution effect
on the chemoselectivity of the rhodium(II)-catalyzed
cyclization has been investigated. The studies reveal that most
of the α-acetyl substrates can exclusively undergo aromatic
2
reaction mixture was stirred at room temperature until TLC
analysis showed full consumption of the starting material. The
solution was then concentrated under reduced pressure, and
the crude residue was purified by flash chromatography on
silica gel (ethyl acetate/hexane) to afford the product(s).
Ethyl 10-hydroxyphenanthrene-9-carboxylate (4a) and ethyl
substitution, except for that bearing
a strong electron-
donating group at the para-position of the phenyl ring as it
showing a complete selectivity for aromatic cycloaddition.
Besides, all of the carboxylate substrates give the mixtures of
two functional isomers from both processes, and mostly in
1
0-oxo-9a,10-dihydrobenzo[a]azulene-9a-carboxylate (5a).
6
| J. Name., 2012, 00, 1-3
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ARTICLE
The titled compounds were prepared from 3a by using δ 7.78 (d, J = 7.40 Hz, 2 H), 7.51 (t, J = 7.40 Hz, 1 H), 7.40 (m, 11
1
3
Rh
2 4 3
(oct) as the catalyst (Table 1, entry 2). Chromatographic H), 4.25 (s, 2 H) ppm; C NMR (100 MHz, CDCl ) δ 198.3,
purification (hexane-EtOAc 50:1, 40:1, 20:1) afforded 4a (47%) 142.4, 141.3, 136.7, 133.0, 132.4, 130.7, 130.2, 129.2, 128.5,
3
2
1
33 1
followed by 5a (41%). 4a
:
H NMR (300 MHz, CDCl
s, 1 H), 8.81 (dd, J = 8.5, 1.2 Hz, 1 H), 8.58-8.55 (m, 3 H), 7.77 MHz, CDCl
ddd, J = 8.3, 7.1, 1.4 Hz, 1 H), 7.64 (ddd, J = 8.1, 7.1, 1.4 Hz, 1 H), 7.64 (dd, J = 7.56, 7.36 Hz, 1 H), 7.53 (dd, J = 7.68, 7.36 Hz,
3
) δ 13.3 128.3, 128.3, 127.6, 127.2, 127.0, 43.3 ppm.
7
:
H NMR (400
(
(
3
) δ 7.94 (d, J = 7.68 Hz, 1 H), 7.78 (d, J = 7.60 Hz, 2
H), 7.58 (ddd, J = 8.5, 7.0, 1.4 Hz, 1 H), 7.49 (ddd, J = 8.1, 7.0, 2 H), 7.41 (d, J = 7.56 Hz, 1 H), 7.35 (dd, J = 7.72, 7.64 Hz, 2 H),
1
.4 Hz, 1 H), 4.62 (q, J = 7.1 Hz, 2 H), 1.56 (t, J = 7.1 Hz, 3 H) 7.21-7.19 (m, 2 H), 7.05-7.04 (m, 3 H) ppm; C NMR (100 MHz,
3
1
1
3
ppm; C NMR (75 MHz, CDCl
3
) δ 172.9, 162.7, 133.7, 130.4, CDCl
29.5, 127.6, 126.8, 126.1, 126.0, 125.3, 125.0, 124.2, 122.9, 130.4, 129.8, 128.3, 128.1, 128.0, 127.7 ppm.
22.4, 101.6, 62.0, 14.4 ppm. 5a (yellow oil): IR (neat) 3019, Ethyl 10-hydroxy-7-methylphenanthrene-9-carboxylate (4d)
3
) δ 195.6, 191.3, 143.6, 139.7, 135.1, 133.9, 132.8, 130.6,
1
1
1
-1
1
745, 1714, 1598, 1209, 765, 703 cm ; H NMR (400 MHz, and ethyl 7-methyl-10-oxo-9a,10-dihydrobenzo[a]azulene-9a-
) δ 7.78-7.75 (m, 2 H), 7.64 (t, J = 7.5 Hz, 1 H), 7.41 (t, J = carboxylate (5d). The titled compounds were prepared from
.5 Hz, 1 H), 6.93 (d, J = 6.0 Hz, 1 H), 6.60-6.43 (m, 3 H), 5.91 3d by using Rh (oct) as the catalyst. The reaction proceeded
d, J = 9.7 Hz, 1 H), 4.04 (q, J = 7.1 Hz, 2 H), 1.09 (t, J = 7.1 Hz, 3 for 20 hours at rt. Chromatographic purification (hexane-EtOAc
CDCl
3
7
2
4
(
1
3
H) ppm; C NMR (100 MHz, CDCl
3
) δ 198.5, 167.0, 149.0, 50:1, 20:1, 5:1) afforded 4d (22%) as a white solid followed by
1
1
35.9, 134.1, 133.5, 131.7, 129.3, 129.2, 129.2, 125.9, 125.0, 5d (69%) as a yellow oil. 4d: m.p. 119-120 °C; IR (neat) 3210,
+
-1
1
22.1, 118.3, 64.2, 61.9, 13.9 ppm; HRMS-EI: m/z [M] calcd. 3079, 1717, 1633, 1615, 1590, 766, 722 cm ; H NMR (400
: 266.0943; found: 266.0950. MHz, CDCl ) δ 13.26 s, 1 H), 8.60 (s, 1 H), 8.55-8.51 (m, 2 H),
-(10-Hydroxyphenanthren-9-yl)ethanone (4b) The titled 8.44 (d, J = 8.4 Hz, 1 H), 7.73 (ddd, J = 8.4, 7.0, 1.2 Hz, 1 H),
compound was prepared from 3b by using Rh (OAc) (Table 1, 7.60 (ddd, J = 8.1, 7.0, 1.0 Hz, 1 H), 7.31 (dd, J = 8.3, 1.4 Hz, 1
entry 4) or Rh (oct) (Table 1, entry 5) as the catalyst. H), 4.61 (q, J = 7.2 Hz, 2 H), 2.54 (s, 3 H), 1.57 (t, J = 7.2 Hz, 3 H)
Chromatographic purification (hexane-EtOAc 30:1, 15:1) ppm; C NMR (100 MHz, CDCl
for C17
H
14
O
3
3
(
1
.
2
4
2
4
1
3
3
) δ 172.9, 162.7, 137.2, 133.7,
3
) δ 14.72 130.3, 129.6, 126.4, 126.0, 125.7, 124.9, 124.9, 123.9, 122.7,
1
7g
1
afforded 4b in 74% yield. H NMR (400 MHz, CDCl
+
(
br s, 1 H), 8.57-8.51 (m, 3 H), 7.98 (d, J = 8.1 Hz, 1 H), 7.77 122.2, 101.4, 61.9, 22.2, 14.3 ppm; HRMS-EI: m/z [M] calcd.
ddd, J = 8.4, 7.0, 1.1 Hz, 1 H), 7.63 (dd, J = 7.6, 7.1 Hz, 1 H), for C18 : 280.1099; found: 280.1097. 5d: IR (neat) 3020,
.56 (ddd, J = 8.1, 7.0, 1.1 Hz, 1 H), 7.49 (dd, J = 8.4, 7.2 Hz, 1 1746, 1714, 1623, 1470, 1212, 765, 739 cm ; H NMR (400
(
16 3
H O
-1
1
7
1
3
H), 2.83 (s, 3 H) ppm; C NMR (100 MHz, CDCl
3
3
) δ 204.1, MHz, CDCl ) δ 7.72-7.68 (m, 2 H), 7.57 (dd, J = 7.7, 7.4 Hz, 1 H),
1
1
9
63.2, 134.2, 131.0, 129.8, 127.2, 127.1, 126.2, 125.6, 125.5, 7.33 (dd, J = 7.4, 7.4 Hz, 1 H), 6.77 (d, J = 6.5 Hz, 1 H), 6.33 (d, J
25.4, 124.6, 123.4, 122.5, 112.3, 31.7 ppm.
= 6.5 Hz, 1 H), 6.26 (d, J = 10.0 Hz, 1 H), 5.82 (d, J = 10.0 Hz, 1
The titled H), 4.00 (q, J = 7.08 Hz, 2 H), 2.02 (s, 3 H), 1.05 (t, J = 7.08 Hz, 3
a-Acetylbenzo[a]azulen-10(9aH)-one (5b)
.
1
3
compound was obtained from 3b by using Rh
2 2 3
(esp) as the H) ppm; C NMR (100 MHz, CDCl ) δ 198.8, 167.2, 149.3,
catalyst (Table 1, entry 6). Chromatographic purification 141.4, 135.8, 133.9, 132.7, 131.7, 128.9, 126.2, 124.8, 124.8,
+
(
hexane-EtOAc 20:1, 10:1) afforded 5b (18%) as a yellow oil 121.8, 118.2, 63.8, 61.7, 24.8, 13.9 ppm; HRMS-EI: m/z [M]
along with 40% of 4b 5b: IR (neat) 3017, 1710, 1703, 1598, calcd. for C18 : 280.1099; found: 280.1092.
62, 707 cm ; H NMR (400 MHz, CDCl ) δ 7.80 (d, J = 7.8 Hz, 1 Ethyl 7-fluoro-10-hydroxyphenanthrene-9-carboxylate (4e)
H), 7.75 (d, J = 7.7 Hz, 1 H), 7.65 (dd, J = 7.8, 7.4 Hz, 1 H), 7.42 and ethyl 7-fluoro-10-oxo-9a,10-dihydrobenzo[a]azulene-9a-
dd, J = 7.7, 7.4 Hz, 1 H), 7.01 (d, J = 6.5 Hz, 1 H), 6.59-6.55 (m, carboxylate (5e). The titled compounds were prepared from
H), 6.46-6.39 (m, 2 H), 6.12 (d, J = 9.8 Hz, 1 H), 2.20 (s, 3 H) 3e by using Rh (oct) as the catalyst. The reactions was carried
) δ 199.4, 198.0, 149.0, 135.9, out for 18 hours at rt. Chromatographic purification (hexane-
34.8, 133.8, 130.5, 130.2, 129.4, 128.7, 127.0, 124.9, 122.0, EtOAc 40:1, 20:1, 10:1) afforded 4e (13%) as a white solid
.
16 3
H O
-
1 1
7
3
(
1
2
4
1
3
ppm; C NMR (100 MHz, CDCl
3
1
1
2
+
18.7, 72.9, 26.4 ppm; HRMS-EI: m/z [M] calcd. for C16
H
12
O
2
:
followed by 5e (89%) as a yellow solid. 4e: m.p. 133-135 °C; IR
-
36.0837; found: 236.0833.
(neat) 3013, 1631, 1618, 1579, 1319, 1313, 1236, 808, 755 cm
1
1
(
10-Hydroxyphenanthren-9-yl)-phenylmethanone (4c), 2-
3
; H NMR (400 MHz, CDCl ) δ 13.50 (s, 1 H), 8.50-8.39 (m, 4 H),
(
[1,1'-biphenyl]-2-yl)-1-phenylethanone (6)
,
and 1-([1,1'- 7.72 (ddd, J = 8.3, 7.0, 1.2 Hz, 1 H), 7.59 (ddd, J = 8.2, 7.0, 1.2
. The titled Hz, 1 H), 7.19 (m, 1 H), 4.60 (q, J = 7.1 Hz, 2 H), 1.57 (t, J = 7.1
biphenyl]-2-yl)-2-phenylethane-1,2-dione (7)
compounds were obtained from 3c by using Rh
catalyst (Table 1, entry 7). Chromatographic purification (d, JC-F = 242.4 Hz), 133.3, 131.3, 131.2, 130.8, 126.6, 125.1,
1
3
2
4 3
(OAc) as the Hz, 3 H) ppm; C NMR (100 MHz, CDCl ) δ 172.7, 164.0, 162.2
(
hexane-EtOAc 50:1, 30:1) afforded 4c (26%) along with 124.8 (d, JC-F = 9.5 Hz), 122.6 (d, JC-F = 2.0 Hz), 122.2, 122.5 (d,
1
7h 1
compounds
6
(35%) and
7
(33%). 4c
:
H NMR (400 MHz,
JC-F = 23.4 Hz), 111.5 (d, JC-F = 25.3 Hz), 101.0 (d, JC-F = 2.4 Hz),
1
9
CDCl
J = 8.24, 1 H), 7.84 dd, J = 8.2, 7.2 Hz, 1 H), 7.69 (dd, J = 7.8, 7.4 HRMS-EI: m/z [M] calcd. for C17
Hz, 1 H), 7.63 (d, J = 7.4 Hz, 2 H), 7.56 (dd, J = 7.6, 7.5 Hz, 1 H), 284.0852. 5e: m.p. 88-90 °C; IR (neat) 3040, 1746, 1717, 1645,
3
) δ 12.73 (br s, 1 H), 8.61 (dd, J = 9.2, 9.0 Hz, 2 H), 8.54 (d, 62.3, 14.3 ppm; F NMR (376 MHz, CDCl
3
) δ -112.8 ppm;
+
H
13FO : 284.0849; found:
3
1
3
-1 1
7
.42-7.34 (m, 4 H), 7.17 (dd, J = 7.4, 7.8 Hz, 1 H) ppm; C NMR 1599, 1226, 764, 744 cm ; H NMR (400 MHz, CDCl
100 MHz, CDCl ) δ 200.2, 160.6, 140.4, 134.0, 132.4, 130.6, 7.75 (m, 2 H), 7.66 (dd, J = 7.6, 7.5 Hz, 1 H), 7.42 (dd, J = 7.5,
30.3, 129.4, 128.5, 127.7, 127.1, 126.1, 125.9, 125.3, 125.1, 7.40 Hz, 1 H), 6.85 (dd, J = 7.2, JH-F = 6.0 Hz, 1 H), 6.44 (ddd, J=
3
) δ 7.79-
(
3
1
1
2
:
1 1
24.4, 122.8, 122.6, 111.0 ppm.
6
H NMR (400 MHz, CDCl
3
)
10.5, JH-F = 8.74, J = 1.64 Hz, 1 H), 6.32 (ddd, JH-F = 17.0, J = 7.8, J
J. Name., 2013, 00, 1-3 | 7
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Journal Name
=
7
1.1 Hz, 1 H), 6.08 (dd, J = 10.5, JH-F = 5.0 Hz, 1 H), 4.07 (q, J = 164.3, 161.7 (d, JC-F = 244.6 Hz), 133.7, 131.5, 131.4, 126.9,
1
3
.0 Hz, 2 H), 1.12 (t, J = 7.0 Hz, 3 H) ppm; C NMR (100 MHz, 125.6 (d, JC-F = 9.2 Hz), 125.5, 125.0, 122.6 (d, JC-F = 1.7 Hz),
) δ 197.7, 165.1 (d, JC-F = 290.2 Hz), 161.2, 148.9, 136.1, 122.3, 112.7 (d, JC-F = 22.8 Hz), 111.5 (d, JC-F = 2.8 Hz), 110.8 (d,
CDCl
3
1
C-F = 23.5 Hz), 31.7 ppm; F NMR (376 MHz, CDCl
9
1
1
1
33.7, 130.6 (d, JC-F = 3.4 Hz), 129.3, 128.1 (d, JC-F = 13.3 Hz),
J
3
) δ -112.4
+
25.1, 124.2 (d, JC-F = 36.6 Hz), 122.0, 115.3 (d, JC-F = 11.6 Hz), ppm; HRMS-EI: m/z [M] calcd. for C16
H11FO : 254.0743; found:
2
1
10.2 (d, JC-F = 28.6 Hz), 64.0, 62.2, 13.9 ppm; F NMR (376 254.0733.
9
+
) δ -95.3 ppm; HRMS-EI: m/z [M] calcd. for 9a-Acetyl-7-methoxybenzo[a]azulen-10(9aH)-one (5i)
MHz, CDCl
3
.
The
as
C
17
H13FO
3
: 284.0849; found: 284.0847.
titled compound was prepared from 3i by using Rh (OAc)
2
4
Ethyl 10-hydroxy-7-methoxyphenanthrene-9-carboxylate (4f) the catalyst. The reaction proceeded for 15 hours at rt.
and ethyl 7-methoxy-10-oxo-9a,10-dihydrobenzo[a]azulene- Chromatographic purification (hexane-EtOAc 50:1, 20:1, 10:1)
9
a-carboxylate (5f). The titled compounds were prepared from afforded 5i (79%) as a yellow oil. IR (neat) 3011, 1728, 1704,
-1 1
3
f
by using Rh
for 24 hours at rt. Chromatographic purification (hexane-EtOAc (m, 2 H), 7.61 (dd, J = 7.8, 7.4 Hz, 1 H), 7.33 (dd, J = 7.5, 7.4 Hz,
0:1, 10:1, 5:1) afforded trace amount of 4f 5%) followed 1 H), 6.93 (d, J = 7.6 Hz, 1 H), 6.29 (d, J = 10.6 Hz, 1 H), 6.19 (d, J
by 5f (92%) as a yellow oil. 4f: IR (neat) 3001, 2923, 1634, 1615, = 10.6 Hz, 1 H), 5.75 (d, J = 7.6 Hz, 1 H), 3.64 (s, 3 H), 2.17 (s, 3
2 4 3
(oct) as the catalyst. The reaction proceeded 1625, 1219, 759, 726 cm ; H NMR (400 MHz, CDCl ) δ 7.73
2
(～
-1
1
13
1
1
7
9
=
1
1
3 3
319, 1243, 853 761 cm ; H NMR (400 MHz, CDCl ) δ 13.43 (s, H) ppm; C NMR (100 MHz, CDCl ) δ 199.5, 198.1, 160.1,
H), 8.53-8.47 (m, 3 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.74 (dd, J = 149.8, 135.9, 133.1, 129.0, 128.4, 127.9, 127.3, 124.9, 121.4,
+
.16, 7.16 Hz, 1 H), 7.57 (dd, J = 7.3, 7.3 Hz, 1 H), 7.13 (dd, J = 117.6, 102.6, 72.3, 54.9, 26.3 ppm; HRMS-EI: m/z [M] calcd.
.0 2.4 Hz, 1 H), 4.61 (q, J = 7.1 Hz, 2 H), 3.95 (s, 3 H), 1.58 (t, J for C17
H
14
O
3
: 266.0943; found: 266.0951.
) δ 173.0, 163.7 1-(10-Hydroxy-6-methylphenanthren-9-yl)ethanone (4j). The
59.1, 133.9, 131.0, 130.6, 125.8, 125.0, 124.3, 124.2, 121.9, titled compound was prepared from 3j by using Rh (OAc) as
20.2, 133.6, 108.1, 101.2, 62.0, 55.2, 14.4 ppm; HRMS-EI: m/z the catalyst. The reaction proceeded for 24 hours at rt.
1
3
7.1 Hz, 3 H) ppm; C NMR (100 MHz, CDCl
3
2
4
+
[M] calcd. for C18
16 4
H O : 296.1049; found: 296.1053. 5f: IR Chromatographic purification (hexane-EtOAc 30:1) afforded 4j
-1 1
(
(
neat) 3071, 1742, 1712, 1221, 1194, 820, 763 cm ; H NMR (83%) as a pale yellow solid. M.p. 81-83 °C; IR (neat) 3060,
-1
1
400 MHz, CDCl
H), 7.61 (dd, J
Hz, 1 H), 6.86 (d, J = 7.5 Hz, 1 H), 6.33 (dd, J
3
) δ 7.74 (d, J = 7.7 Hz, 1 H), 7.71 (d, J = 7.9 Hz, 3016, 1600, 1574, 1224, 812, 772 cm ; H NMR (400 MHz,
= 7.7, J = 7.3 Hz, 1 H), 7.34 (dd, J = 7.9, J = 7.3 CDCl ) δ 14.66 (s, 1 H), 8.54 (d, J = 8.2 Hz, 2 H), 8.34 (s, 1 H),
= 10.5, J = 1.8 Hz, 7.89 (d, J = 8.4 Hz, 1 H), 7.76 (dd, J = 8.2, 7.7 Hz, 1 H), 7.62 (dd,
H), 6.02 (d, J = 10.5 Hz, 1 H), 5.78 (br d, J = 7.5 Hz, 1 H), 4.12- J = 8.2, 7.7 Hz, 1 H), 7.39 (d, J = 8.4 Hz, 1 H), 2.82 (s, 3 H), 2.57
1
1
2
1
2
3
1
2
1
4
1
3
13
.01 (m, 2 H), 3.66 (s, 3 H), 1.09 (t, J = 7.1 Hz, 3 H) ppm;
C
3
(s, 3 H) ppm; C NMR (100 MHz, CDCl ) δ 204.0, 162.4, 134.1,
NMR (100 MHz, CDCl
3
) δ 198.6, 167.1, 160.9, 149.7, 135.8, 134.0, 130.9, 128.7, 127.4, 127.0, 126.2, 125.6, 125.4, 125.4,
+
33.4, 128.2, 128.1, 127.6, 126.9, 124.9, 121.4, 117.2, 102.1, 123.3, 122.5, 112.1, 31.8, 21.5 ppm; HRMS-EI: m/z [M] calcd.
1
+
6
3.6, 61.8, 54.9, 13.9 ppm; HRMS-EI: m/z [M] calcd. for for C17
: 296.1049; found: 296.1049. 1-(6-Chloro-10-hydroxyphenanthren-9-yl)ethanone (4k). The
-(10-Hydroxy-7-methylphenanthren-9-yl)ethanone (4g). The titled compound was prepared from 3k by using Rh (OAc) as
titled compound was prepared from 3g by using Rh (OAc) as the catalyst. The reaction proceeded for 24 hours at rt.
14 2
H O : 250.0994; found: 250.1020.
18 16 4
C H O
1
2
4
2
4
the catalyst. The reaction proceeded for 24 hours at rt. Chromatographic purification (hexane-EtOAc 40:1) afforded 4k
Chromatographic purification (hexane-EtOAc 60:1, 30:1) (96%) as a yellow solid. M.p. 133-135 °C; IR (neat) 3087, 3038,
-
1 1
afforded 4g (50%) as a yellow solid. M.p. 88-90 °C; IR (neat) 1593, 1568, 1246, 807, 769 cm ; H NMR (400 MHz, CDCl
3
) δ
060, 1615, 1593, 1574, 1236, 765, 725 cm ; H NMR (400 14.74 (s, 1 H), 8.44 (d, J = 8.0 Hz, 1 H), 8.30 (d, J = 2.0 Hz, 1 H),
MHz, CDCl ) δ 14.63 ( s, 1 H), 8.53 (d, J = 8.2 Hz, 1 H), 8.49 (d, J 8.27 (d, J = 8.3 Hz, 1 H), 7.78 (d, J = 8.9 Hz, 1 H), 7.70 (ddd, J =
8.3 Hz, 1 H), 8.42 (d, J = 8.4 Hz, 1 H), 7.76 (br s, 1 H), 7.75 (dd, 8.3, 7.1, 1.1 Hz, 1 H), 7.59 (ddd, J = 8.0, 7.1, 1.1 Hz, 1 H), 7.41
-1
1
3
3
=
1
3
J = 7.4 Hz, 1 H), 7.60 (dd, J = 8.2, 7.6 Hz, 1 H), 7.32 (d, J = 8.3 (dd, J = 8.9, 2.1 Hz, 1 H), 2.73 (s, 3 H) ppm; C NMR (100 MHz,
1
3
Hz, 1 H), 2.83 (s, 3 H), 2.55 (s, 3 H) ppm; C NMR (100 MHz, CDCl
CDCl ) δ 203.9, 162.9, 137.0, 134.2, 130.9, 129.9, 126.6, 126.0, 127.3, 126.5, 125.7, 125.4, 122.9, 122.4, 111.4, 31.8 ppm;
2
25.6, 125.4, 125.1, 124.0, 123.2, 122.2, 112.1, 31.7, 21.9 ppm; HRMS-EI: m/z [M] calcd. for C16H11ClO : 270.0448; found:
3
) δ 203.5, 163.1, 132.8, 131.1, 130.4, 128.0, 127.9, 127.7,
3
+
1
+
HRMS-EI: m/z [M] calcd. for C17
H
14
O
2
: 250.0994; found: 270.0439.
1-(5-Hydroxyphenanthro[2,3-d][1,3]dioxol-6-yl)ethanone (4l).
-(7-Fluoro-10-hydroxyphenanthren-9-yl)ethanone (4h). The The titled compound was prepared from 3l by using Rh (oct)
(OAc) as as the catalyst. The reaction proceeded for 24 hours at rt.
2
50.0986.
1
2
4
titled compound was prepared from 3h by using Rh
2
4
the catalyst. The reaction proceeded for 18 hours at rt. Chromatographic purification (hexane-EtOAc 10:1, 5:1)
Chromatographic purification (hexane-EtOAc 30:1) afforded 4h afforded 4l (88%) as a yellow solid. M.p. 170-172 °C; IR (neat)
-
(
39%) as a pale yellow solid. M.p. 131-133 °C; IR (neat) 3015, 3074, 1621, 1597, 1575, 1252, 1236, 1204, 1039, 862, 777 cm
-1
1
1 1
1
616, 1595, 1579, 1227, 1192, 990, 871, 765 cm ; H NMR
) δ 14.96 (s, 1 H), 8.51 (dd, J = 8.3, 0.7 Hz, 1 H), 1 H), 8.28 (d, J = 8.3 Hz, 1 H), 7.86 (s, 1 H), 7.71 (ddd, J = 8.3,
.47 (dd, J = 9.0, JH-F = 6.1 Hz, 1 H), 8.40 (d, J = 8.3 Hz, 1 H), 7.76 7.1, 1.0 Hz, 1 H), 7.56 (ddd, J = 8.0, 7.1, 1.0 Hz, 1 H), 7.32 (s, 1
3
; H NMR (400 MHz, CDCl ) δ 14.21 (s, 1 H), 8.49 (d, J = 8.0 Hz,
(400 MHz, CDCl
3
8
1
3
3
(ddd, J = 8.3, 7.2, 1.2 Hz, 1 H), 7.63-7.58 (m, 2 H), 7.23-7.18 (m, H), 6.09 (s, 2 H), 2.77 (s, 3 H) ppm; C NMR (100 MHz, CDCl ) δ
1
H), 2.81 (s, 3 H) ppm; C NMR (100 MHz, CDCl
3
1
3
) δ 203.6, 203.9, 161.2, 148.0, 146.0, 133.8, 130.7, 126.2, 125.6, 125.4,
8
| J. Name., 2012, 00, 1-3
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ARTICLE
+
24.5, 122.2, 121.7, 112.9, 104.2, 101.9, 101.6, 31.7 ppm; 119.1, 115.1, 103.4, 55.3, 48.4 ppm; HRMS-EI: m/z [M] calcd.
1
+
12 4 2
HRMS-EI: m/z [M] calcd. for C17H O : 280.0736; found: for C16H11NO : 249.0790; found: 249.0787.
2
80.0729.
0-Oxo-9a,10-dihydrobenzo[a]azulene-9a-carbonitrile (5m)
(oct)
10-Hydroxy-6-methylphenanthrene-9-carbonitrile (4q) and
1
.
10-hydroxy-8-methylphenanthrene-9-carbonitrile (4q'). The
The titled compound was prepared from 3m by using Rh
2
4
2 4
titled compounds were prepared from 3q by using Rh (oct) as
as the catalyst. The reaction proceeded for 24 hours at rt. the catalyst. The reaction proceeded for 22 hours at rt.
Chromatographic purification (hexane-EtOAc 10:1, 5:1) Chromatographic purification (hexane-EtOAc 8:1, 5:1; then
afforded 5m (91%) as a yellow oil. IR (neat) 3236, 2226, 1729, EtOAc-MeOH 30:1) afforded 4q and 4q' as a regioisomeric
-
1 1
1
596, 761, 705 cm ; H NMR (400 MHz, CDCl
3
) δ 7.86 (d, J = mixture (87%; 4q/4q' = 74/26; white solid). M.p. 198-215 °C
7
.7 Hz, 1 H), 7.77-7.70 (m, 2 H), 7.50 (ddd, J = 7.7, 6.2, 1.5 Hz, 1 (mixture); IR (neat) 3262, 2224, 2223, 1614, 1592, 1258, 1228,
-1 1
H), 6.99 (d, J = 6.3 Hz, 1 H), 6.87 (dd, J = 11.3, 6.3 Hz, 1 H), 6.78 763, 751 cm ; H NMR (400 MHz, DMSO-d6) 4q: δ 11.64 (br s,
dd, J = 11.3, 6.2 Hz, 1 H), 6.51 (dd, J = 9.5, 6.2 Hz, 1 H), 5.73 (d, 1 H), 8.82 (d, J = 8.3 Hz, 1 H), 8.56 (s, 1 H), 8.41 (d, J = 8.1 Hz, 1
(
1
3
J = 9.5 Hz, 1 H) ppm; C NMR (100 MHz, CDCl
3
) δ 194.5, 147.1, H), 7.87-7.80 (m, 2 H), 7.77-7.71 (m, 1 H), 7.53 (d, J = 8.2 Hz, 1
1
1
37.0, 133.2, 132.4, 131.3, 130.7, 130.3, 128.7, 125.7, 122.5, H), 2.53 (s, 3 H) ppm; 4q': δ 11.64 (br s, 1 H), 8.82 (d, J = 8.3 Hz,
+
21.4, 119.7, 114.7, 49.0 ppm; HRMS-EI: m/z [M] calcd. for 1 H), 8.66-8.62 (m, 1 H), 8.41 (d, J = 8.1 Hz, 1 H), 7.87-7.80 (m,
NO: 219.0684; found: 219.0678. 1 H), 7.77-7.71 (m, 1 H), 7.46-7.44 (m, 2 H), 2.95 (s, 3 H) ppm;
-Methyl-10-oxo-9a,10-dihydrobenzo[a]azulene-9a-
carbonitrile (5n). The titled compound was prepared from 3n 130.6, 127.8, 127.5, 125.8, 125.3, 124.1, 124.0, 123.9, 123.6,
by using Rh (oct) as the catalyst. The reaction proceeded for 117.1, 90.6, 21.7 ppm; 4q': δ 161.4, 133.3, 133.0, 131.9, 130.9,
4 hours at rt. Chromatographic purification (hexane-EtOAc 128.3, 127.9, 126.6, 125.6, 124.6, 124.3, 123.9, 122.4, 119.4,
15 9
C H
1
3
7
C NMR (100 MHz, DMSO-d6) 4q: δ 158.4, 135.4, 132.7, 130.6,
2
4
2
1
+
2:1, 5:1) afforded 5n (89%) as a yellow solid. M.p. 221-224 °C; 89.9, 23.3 ppm; HRMS-EI: m/z [M] calcd. for C16H11NO:
-1 1
IR (neat) 3013, 2233, 1723, 1596, 762, 740 cm ; H NMR (400 233.0841; found: 233.0836.
MHz, CDCl ) δ 7.84 (d, J = 7.8 Hz, 1 H), 7.74-7.67 (m, 2 H), 7.46 6-Chloro-10-hydroxyphenanthrene-9-carbonitrile (4r) and 6-
ddd, J = 7.8, 5.6, 2.2 Hz, 1 H), 6.89 (d, J = 6.6 Hz, 1 H), 6.66 (d, J chloro-10-oxo-9a,10-dihydrobenzo[a]azulene-9a-carbonitrile
3
(
=
2
1
1
6.6 Hz, 1 H), 6.36 (d, J = 9.6 Hz, 1 H), 5.68 (d, J = 9.6 Hz, 1 H), (5r). The titled compounds were prepared from 3r by using
1
3
3 2 4
.21 (s, 3 H) ppm; C NMR (100 MHz, CDCl ) δ 194.7, 147.4, Rh (oct) as the catalyst. The reaction proceeded for 2.5 hours
42.4, 136.9, 134.6, 133.0, 129.8, 127.7, 126.8, 125.6, 122.2, at rt. Chromatographic purification (hexane-EtOAc 10:1, 5:1;
+
20.4, 119.7, 115.1, 48.6, 24.9 ppm; HRMS-EI: m/z [M] calcd. then EtOAc-MeOH 30:1, 20:1, 5:1) afforded 4r (56%) followed
for C16
-Fluoro-10-oxo-9a,10-dihydrobenzo[a]azulene-9a-
carbonitrile (5o). The titled compound was prepared from 3o δ 12.02 (br s, 1 H), 8.89 (d, J = 8.3 Hz, 1 H), 8.84 (s, 1 H), 8.44
by using Rh (oct) as the catalyst. The reaction proceeded for (d, J = 8.0 Hz, 1 H), 7.93-7.84 (m, 2 H), 7.83-7.76 (m, 1 H), 7.74
4 hours at rt. Chromatographic purification (hexane-EtOAc (d, J = 8.7 Hz, 1 H) ppm; C NMR (100 MHz, DMSO-d6) δ159.8,
0:1, 5:1) afforded 5o (97%) as a yellow solid. M.p. 153-155 °C; 131.9, 131.1, 130.8, 129.2, 128.6, 128.6, 127.0, 126.0, 125.7,
H11NO: 233.0841; found: 233.0845.
by 5r (44%) as white solids. 4r: m.p. 307-309 °C; IR (neat) 3229,
-1 1
7
2226, 1615, 1589, 813, 767 cm ; H NMR (400 MHz, DMSO-d6)
2
4
1
3
2
1
-1
1
+
IR (neat) 3045, 2236, 1729, 1627, 841, 762 cm ; H NMR (400 124.5, 124.3, 123.5, 116.8, 90.0 ppm; HRMS-EI: m/z [M] calcd.
MHz, CDCl ) δ 7.86 (d, J = 7.8 Hz, 1 H), 7.77-7.71 (m, 2 H), 7.55- for C15 ClNO: 253.0294; found: 253.0293. 5r: m.p. 314-316 °C;
.47 (m, 1 H), 6.95 (dd, J = 7.5, JH-F = 5.7 Hz, 1 H), 6.62 (ddd, JH-F IR (neat) 3066, 2238, 1731, 790, 765, 747 cm ; H NMR (400
16.5, J = 7.5, 1.7 Hz, 1 H), 6.53 (ddd, J = 10.1, JH-F = 8.4, J = 1.7 MHz, CDCl ) δ7.88 (d, J = 7.8 Hz, 1 H), 7.80-7.75 (m, 2 H), 7.61-
3
H
8
-1 1
7
=
3
1
3
Hz, 1 H), 5.90 (dd, J = 10.1, JH-F = 5.0 Hz, 1 H) ppm; C NMR 7.53 (m, 1 H), 6.97 (s, 1 H), 6.93 (dd, J = 7.0, 0.6 Hz, 1 H), 6.44
1
3
(
100 MHz, CDCl
3
) δ 193.5, 162.2 (d, JC-F = 250.4 Hz), 147.0, (dd, J = 9.4, 7.0 Hz, 1 H), 5.73 (d, J = 9.4 Hz, 1 H) ppm; C NMR
37.2, 132.8, 130.3, 126.4 (d, JC-F = 36.9 Hz), 125.8, 125.8, (100 MHz, CDCl ) δ 193.4, 145.8, 137.3, 135.9, 133.5, 131.3,
23.4 (d, JC-F = 13.0 Hz), 122.4, 117.1 (d, JC-F = 11.4 Hz), 114.4, 130.5, 130.0, 129.7, 125.9, 122.9, 121.3, 121.0, 114.3, 48.5
1
1
1
3
1
9
+
12.2 (d, JC-F = 28.9 Hz), 48.6 ppm; F NMR (376 MHz, CDCl
3
) δ ppm; HRMS-EI: m/z [M] calcd. for C15
FNO: 237.0590; found: 253.0297.
5-Hydroxyphenanthro[2,3-d][1,3]dioxole-6-carbonitrile (4s)
The titled compound was prepared from 3s by using Rh (oct)
carbonitrile (5p). The titled compound was prepared from 3p as the catalyst. The reaction proceeded for 2.5 hours at rt.
by using Rh (oct) as the catalyst. The reaction proceeded for Chromatographic purification (hexane-EtOAc 8:1; then EtOAc-
4 hours at rt. Chromatographic purification (hexane-EtOAc MeOH 10:1, 5:1) afforded 4s (97%) as a white solid. M.p. 287-
0:1, 5:1) afforded 5p (quant.) as a yellow oil. IR (neat) 3010, 289 °C; IR (neat) 3269, 2913, 2225, 1592, 1238, 1039, 859, 758
8
H ClNO: 253.0294;
+
-
92.7 ppm; HRMS-EI: m/z [M] calcd. for C15H
8
found: 237.0596.
.
7
-Methoxy-10-oxo-9a,10-dihydrobenzo[a]azulene-9a-
2
4
2
4
2
1
2
-1
1
-1 1
234, 1721, 1630, 1596, 1234, 759, 725 cm ; H NMR (400 cm ; H NMR (400 MHz, DMSO-d6) δ 11.51 (br s, 1 H), 8.67 (d,
) δ 7.82 (d, J = 7.8 Hz, 1 H), 7.72-7.64 (m, 2 H), 7.46- J = 8.4 Hz, 1 H), 8.38 (d, J = 8.2 Hz, 1 H), 8.23 (s, 1 H), 7.76 (dd, J
.38 (m, 1 H), 6.94 (d, J = 7.6 Hz, 1 H), 6.39 (dd, J = 10.2, 1.8 Hz, = 8.4, 7.1 Hz, 1 H), 7.65 (dd, J = 8.2, 7.1 Hz, 1 H), 7.24 (s, 1 H),
MHz, CDCl
3
7
1
3
1
1
3
H), 6.03 (dd, J =7.6, 1.8 Hz, 1 H), 5.84 (d, J = 10.2 Hz, 1 H), 6.20 (s, 2 H) ppm; C NMR (100 MHz, DMSO-d6) δ 157.9,
1
.78 (s, 3 H) ppm; C NMR (100 MHz, CDCl
3
3
) δ 194.5, 161.1, 149.3, 147.5, 132.7, 130.4, 126.8, 126.2, 124.2, 124.1, 124.0,
48.0, 137.0, 132.4, 129.9, 129.2, 125.6, 123.1, 122.5, 121.8, 121.3, 117.2, 102.4, 102.4, 101.7, 91.3 ppm; HRMS-EI: m/z
+
[
9 3
M] calcd. for C16H NO : 263.0582; found: 263.0584.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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DOI: 10.1039/C8OB01489B
ARTICLE
Journal Name
1
0-(Methylsulfonyl)phenanthren-9-ol
phenanthrene-9,10-dione (8). In the typical procedure, the
titled compounds were obtained from 3t by using Rh (oct) as
(4t)
and
Conflicts of interest
There are no conflicts to declare.
2
4
the catalyst (1 mol%, Scheme 10, b). The reaction mixture was
stirred at rt for 24 hours till no consumption of 3s was shown
by TLC analysis. Flash chromatography (hexane-EtOAc 8:1, 6:1)
Acknowledgements
2
9
We are grateful to the Ministry of Science and Technology of
Taiwan, R.O.C. for financial support (MOST 106-2113-M-259-
gave 4t as a pale yellow solid (20%), plus the known
compound (16%) and recovered 3t (52%). 4t: m.p. 153-155
C; IR (neat) 3143, 2925, 1612, 1586, 1575, 1289, 1254, 770,
8
0
04), and Miss Ly-Mei Syu and Mr. Dao-Wen Luo from the
°
-1 1
Department of Chemistry of National Chung Hsing University
for HRMS and x-ray analyses.
7
8
7
3
53, 725 cm ; H NMR (400 MHz, CDCl ) δ 11.70 (br s, 1 H),
.66-8.57 (m, 3 H), 8.55 (d, J = 8.1 Hz, 1 H), 7.83 (ddd, J = 8.1,
.1, 1.0 Hz, 1 H), 7.72-7,63 (m, 2 H), 7.58 (ddd, J = 8.1, 7.1, 1.0
1
3
Hz, 1 H), 3.36 (s, 3 H) ppm; C NMR (100 MHz, CDCl
3
) δ 156.3,
Notes and references
1
1
33.7, 131.0, 128.4, 127.5, 127.2, 126.4, 125.3, 125.2, 125.1,
+
23.4, 123.3, 122.5, 108.7, 44.9 ppm; HRMS-EI: m/z [M] calcd.
1
A. Ford, H. Miel, A. Ring, C. N. Slattery, A. R. Maguire and M.
A. McKervey, Chem. Rev., 2015, 115, 9981.
1
for C15
H
12
O
3
S: 272.0507; found: 272.0509.
) δ 8.18 (dd, J = 7.6, 1.3 Hz, 2 H), 8.01 (d, J = 8.0 Hz,
H), 7.71 (ddd, J = 8.0, 7.6, 1.3 Hz, 2 H), 7.47 (dd, J = 7.6, 7.6
8: H NMR (400
2
For examples, see: (a) R. R. Nani and S. E. Reisman, J. Am.
Chem. Soc., 2013, 135, 7304; (b) O. A. McNamara, N. R.
Buckley, P. O'Leary, F. Harrington, N. Kelly, S. O'Keeffe, A.
Stack, S. O'Neill, S. E. Lawrence, C. N. Slattery and A. R.
Maguire, Tetrahedron, 2014, 70, 6870; (c) A. Padwa and Y,
Zou, J. Org. Chem., 2015, 80, 1802.
MHz, CDCl
3
2
1
3
Hz, 2 H), ppm; C NMR (100 MHz, CDCl
31.1, 130.5, 129.6, 124.0 ppm; HRMS-EI: m/z [M] calcd. for
: 208.0524; found: 208.0519.
0-Tosylphenanthren-9-ol (4u). In the typical procedure, the
titled compound was obtained from 3u by using Rh (oct) as
3
) δ 180.4, 136.0, 135.9,
+
1
14 8 2
C H O
3
For examples, see: (a) E. Rodriguez-Cárdenas, R. Sabala, M.
Romero-Ortega, A. Ortiz and H. F. Olivo, Org. Lett., 2012, 14
2
Tetrahedron, 2013, 69, 1978; (c) S. G. Dawande, V.
1
,
38; (b) H. Fan, Z. Zhang, X. Li, J. Zhao, J. Gao and S. Zhu,
2
4
the catalyst (5 mol%, Scheme 10, d). The reaction mixture was
stirred at rt for 24 hours till no consumption of 3u was shown
by TLC analysis. Flash chromatography (hexane-EtOAc 16:1,
Kanchupalli, J. Kalpu, H. Chennamsetti, B. S. Lad and S.
Katukojvala, Angew. Chem. Int. Ed., 2014, 53, 4076; d) B. Ma,
F.-L. Chen, X.-Y. Xu, Y.-N. Zhang and L.-H. Hu, Adv. Synth.
Catal., 2014, 356, 416; (e) X. Zhang, M. Lei, Y. Zhan and L. Hu,
Tetrahedron, 2014, 70, 3400; (f) D. Best, D. J. Burns and H. W.
Lam, Angew. Chem. Int. Ed., 2015, 54, 7410; (g) P. Huang, Z.
Yan and J. Xu, Tetrahedron, 2017, 73, 3255.
10:1, 8:1) gave 4u as a white solid (11%), along with
8 (17%)
and recovered 3u (15%). 4u: m.p. 139-142 °C; IR (neat) 3132,
-
1
1
923, 1611, 1585, 1255, 1123, 760, 724, 594 cm ; H NMR
2
(400 MHz, CDCl ) δ 12.06 (br s, 1 H), 8.62 (d, J = 8.3 Hz, 1 H),
3
4
5
S. Jia, D. Xing, D. Zhang and W. Hu, Angew. Chem. Int. Ed.,
2
For examples, see: (a) T. K. Hyster, K. E. Ruhl and T. Rovis, J.
Am. Chem. Soc., 2013, 135, 5364; (b) Y. Li, F. Wang, S. Yu and
X. Li, Adv. Synth. Catal., 2016, 358, 880.
8
7
7
7
1
1
2
.57 (d, J = 8.4 Hz, 1 H), 8.55-8.51 (m, 1 H), 8.41-8.36 (m, 1 H),
.86 (d, J = 8.2 Hz, 2 H), 7.81 (ddd, J = 8.4, 7.3, 1.1 Hz, 1 H),
.69 (ddd, J = 8.3, 7.2, 1.1 Hz, 1 H), 7.49-7.42 (m, 2 H), 7.27-
014, 53, 13098.
1
3
3
.23 (m, 2 H), 2.35 (s, 3 H) ppm; C NMR (100 MHz, CDCl ) δ
57.1, 144.6, 139.2, 133.8, 130.9, 130.2, 129.8, 127.8, 127.3,
6
For examples, see: (a) P. J. Pérez, M. M. Díaz-Requejo and I.
Rivilla, Beilstein J. Org. Chem., 2011, 7, 653; (b) Y. Xi, Y. Su, Z.
26.9, 126.7, 126.2, 125.3, 124.9, 123.9, 123.0, 122.5, 108.5,
+
1.5 ppm; HRMS-EI: m/z [M] calcd. for C21
Yu, B. Dong, E. J. McClain, Y. Lan and X. Shi, Angew. Chem.
Int. Ed., 2014, 53, 9817; (c) W. Ai, X. Yang, Y. Wu, X. Wang, Y.
Li, Y. Yang and B. Zhou, Chem. Eur. J., 2014, 20, 17653; (d) Y.
Xia, Z. Liu, S. Feng, Y. Zhang and J. Wang, J. Org. Chem., 2015,
80, 223; (e) Conde, G, Sabenya, M. Rodríguez, V. Postils, J. M.
Luis, M. M. Díaz-Requejo, M. Costas and P. J. Pérez, Angew.
Chem. Int. Ed., 2016, 55, 6530.
H
16
O
3
S: 348.0820;
found: 348.0813.
Procedure for Rh(III)-Catalyzed Reaction of Sulfonyl Diazo
Precursors
To a stirred solution of 3t (44 mg, 0.147 mmol) in 1,2-
dichloroethane (15 mL) under N
.3 mg, 0.0037 mmol) and AgSbF
2
protection, [Cp*RhCl
2
]
2
(99%,
7
(a) A. Padwa, D. J. Austin, A. T. Price, M. A. Semones, M. P.
Doyle, M. N. Protopopova, W. R. Winchester and A. Tran, J.
Am. Chem. Soc., 1993, 115, 8669; (b) M. R. Fructos, T. R.
Belderrain, P. de Frémont, N. M. Scott, S. P. Nolan, M. M.
Díaz-Requejo and P. J. Pérez, Angew. Chem. Int. Ed., 2005,
44, 5284; (c) I. Rivilla, B. P. Gómez-Emeterio, M. R. Fructos,
M. M. Díaz-Requejo and P. J. Pérez, Organometallics, 2011,
30, 2855.
2
6
(98%, 5.1 mg, 0.015 mmol)
were successively added. The mixture was then stirred for 5
hours at reflux, cooled to rt, and concentrated under reduced
pressure. Chromatographic purification of the crude mixture
(hexane-EtOAc 12:1, 8:1, 4:1) afforded 4t in 60% yield (24 mg).
The application of the same procedure to 3u led to the
8
9
(a) M. R. Fructos, T. R. Belderrain, M. C. Nicasio, S. P. Nolan,
H. Kaur, M. M. Díaz-Requejo and P. J. Pérez, J. Am. Chem.
Soc., 2004, 126, 10846; (b) M. R. Fructos, M. Besora, A. A. C.
Braga, M. M. Díaz-Requejo, F. Maseras and P. J. Pérez,
Organometallics, 2017, 36, 172; (c) V. Postils, M. Rodríguez,
G. Sabenya, A. Conde, M. M. Díaz-Requejo, P. J. Pérez, M.
Costas, M. Solà, and J. M. Luis, ACS Catal., 2018, 8, 4313.
A. Ring, A. Ford and A. R. Maguire, Tetrahedron Lett., 2016,
57, 5399.
formation of 4u (56%) and 8 (7%).
Conversion of 4t into 8
Rh
2
(oct)
4
(24 mg, 0.031 mmol) was added to a stirred solution
Cl (7 mL). The reaction
of 4t (17 mg, 0.062 mmol) in CH
2
2
mixture was stirred at rt for 25 hours, and concentrated under
vacuo. The residue was subjected to chromatography (hexane-
EtOAc 8:1, 4:1) to provide 5.33 mg of 8 (41%).
1
0 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C8OB01489B
Journal Name
ARTICLE
1
0 (a) P. M. P. Gois and C. A. M. Afonso, Eur. J. Org. Chem., 2004,
773; (b) M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem.
M. Kennedy, M. A. McKervey, F. M. Twohig, J. Chem. Soc.,
Commun., 1988, 1586.
3
Rev., 2010, 110, 704; (c) H. Li, X. Ma and M. Lei, Dalton 20 G. Cahiz, D. Luart and F. Lecomle, Org. Lett., 2004,
Trans., 2016, 45, 8506.
1 (a) M. P. Doyle, M. S. Shanklin, S.-M. Oon, H. Q. Pho and F.
6
, 4395.
21 M. Lessi, T. Masini, L. Nucara, F. Bellina and R. Rossi, Adv.
Synth. Catal., 2011, 353, 501.
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9 To our knowledge, only the terminal (Scheme 2, X = H, Y = H)
and methyl-substituted (Scheme 2, X = Me, Y = H) biphenyl
α-diazoketones have been investigated for the metal-
catalyzed cyclization in two isolated cases, see: H. Duddeck,
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