A facile and highly atom-economic approach to biaryl-containing medium-ring bislactones

Article abstract of DOI:10.1039/c2cc16492b

Starting from readily available phenanthrenequinone and alkenes, biaryl containing medium-ring bislactones could be easily prepared through sequential photocycloaddition-photooxidation reactions with good yields and diastereoselectivity. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2cc16492b

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COMMUNICATION
A facile and highly atom-economic approach to biaryl-containing
medium-ring bislactonesw
Dongdong Wu,a Lei Wang,a Kai Xu,a Jia Song,a Hoong-Kun Fun,b Jianhua Xua and
Yan Zhang*a
Received 19th October 2011, Accepted 29th November 2011
DOI: 10.1039/c2cc16492b
Starting from readily available phenanthrenequinone and alkenes,
biaryl containing medium-ring bislactones could be easily
prepared through sequential photocycloaddition–photooxidation
reactions with good yields and diastereoselectivity.
Biaryl-containing medium-sized rings are important structural
cores found in many biologically active compounds including
Scheme 1 Reaction sequence leading to biaryl containing ten-membered
bislactones.
natural products as well as in ligands for metal-complex
catalysts.1 Methods to prepare these medium ring biaryls are
of current research interest.2 In general, medium-sized ring
a highly atom-economic way. As shown in Scheme 1, the first
step in the reaction sequence was the photoinduced [4+2]
construction is difficult due to a combination of the unfavorable
cycloaddition of the dione with a CQC bond to form the
dioxinophenanthrene or dioxinophenanthroline (DOP).
Further transformation of the DOP into the biaryl-containing
medium-ring bislactones such as 3a and 5a happened rapidly
upon photoirradiation under an oxygen atmosphere with yields
up to 90%. The reaction is highly atom-economic and no
catalysts or additional photosensitizers were needed in the
reaction sequence.
entropic and enthalpic effect on the cyclization, and the
synthesis of a medium-ring fused with biaryls is further
hampered by the torsional and transannular strain associated
with the biaryl moiety in the ring.3 Spring et al. have developed
an organocuprate oxidation method to prepare biaryl-containing
medium-sized ring bislactones using aryl iodides as the
substrates.4 Other efficient methods to prepare biaryl-containing
medium-sized ring bislactones remain to be explored.
The photocycloaddition reactions of PQ with CQC bonds
were known to give [2+2]8 and [4+4]9 cycloadducts as well as
the DOP type [4+2] cycloadducts.10 The yield of the [4+2]
product DOP 2a from PQ and 1a was found to be highest in
benzene, which was around 95% (ESIw). Conditions for
further transformation of the DOP 2a into the bislactone 3a
were then optimized. As shown in Table 1, formation of 3a
from 2a was highly dependent on the solvent in which photo-
oxidation happened. Polar solvents favored the conversion
of 2a. The yield of 3a could be as high as 91% in the
photooxidation reaction in acetonitrile. The presence of oxygen
accelerated the formation of 3a significantly as shown in entries
5 and 6 in Table 1.
Photochemical methods are efficient in the preparation of
strained molecules and have been used as key steps in natural
product synthesis.5 Photoreactions can also serve as an atom-
economical method to build macro- or medium-ring heterocycles.6
However, photochemical approaches to biaryl-containing
medium-ring lactones have rarely been explored except for a
recent example using the photo-dehydro-Diels–Alder reaction to
prepare (1,5)naphthalenophanes with bislactone functionality.7
Here we report a facile photochemical approach to biaryl-
containing medium-ring bislactones with easily available reactants
via a concise photocycloaddition–photooxidation sequence.
Starting from 9,10-phenanthrenedione (PQ) or 1,10-phenan-
throline-5,6-dione (PN) and alkenes, we were able to prepare
ten-membered bislactones containing biphenyl or bipyridine in
The formation of the bislactones from the DOPs was ratio-
nalized by the addition of oxygen to the electron rich double
bond in the DOPs followed by the cleavage of the dioxetane
intermediate as shown in Scheme 2. To help to clarify the active
oxygen species involved in the photooxygenation reactions,11 the
following control experiments have been carried out. Under
typical singlet oxygen reaction conditions by tetraphenylporphine
(TPP) sensitized photolysis in O2 saturated benzene,12 no obvious
conversion of 2a was observed after irradiation for 24 hours
(Table 1). Furthermore, thermal decomposition of an excess
amount of 1,4-dimethylnaphthalene endoperoxide in acetonitrile
a School of Chemistry and Chemical Engineering, State Key
Laboratory of Analytical Chemistry for Life Science, Nanjing University,
Nanjing, 210093, P. R. China. E-mail: njuzy@nju.edu.cn
b X-Ray Crystallography Unit, School of Physics, Universiti Sains
Malaysia, 11800 USM Penang, Malaysia
w Electronic supplementary information (ESI) available: General
experimental procedures, details of control experiments for
mechanism elucidation, crystal structures of 5e, 3j and 7, compound
data, copies of NMR spectra of the new compounds. CCDC
849063–849065. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c2cc16492b
c
1168 Chem. Commun., 2012, 48, 1168–1170
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Table 1 Optimization of the conditions for the transformation of the
DOP 2a into the bislactone 3a
Table 2 Photooxidation of different substrates
Products
Entry Substrates (yieldsa)
Products
Entry Substrates (yieldsa, d.r.b)
Irradiation
Additive time/h
Yield
Conversion of 3a
Entry Solvent
1
2
3
4
5
6
7
8
O2 saturated PhH
O2 saturated THF
O2 saturated CHCl3
O2 saturated CH3OH —
O2 saturated CH3CN —
Air saturated CH3CN —
—
—
—
24
24
24
6
0
0
0
—
—
—
1
6
7
8
100%
100%
100%
0
13%a
91%
90%
—
6
16
24
24
2
3
O2 saturated PhH
TPPb
O2 saturated CH3CN BQc
0
—
a
b
The other product is shown in ESI. Tetraphenylporphine.
Benzoquinone.
c
4
5
9
10
—
Scheme 2 Proposed pathway for the formation of the bislactones.
a
b
Isolated yield. d.r. based on H NMR of the mixture products.
1
for in situ generation of singlet oxygen13 did not induce the
conversion of 2a (ESIw). The contribution of singlet oxygen to
the transformation of 2a into 3a could therefore be excluded.
On the other hand, the formation of 3a was completely
suppressed in the presence of benzoquinone (BQ) which is an
efficient electron trap for superoxide radical anions14 (ESIw).
This suggests the involvement of superoxide radical anions as
the active oxygen species for the transformation from 2a to 3a.
The ESR spectra of the reaction mixture also indicated the
presence of superoxide radical anions upon photo-irradiation
(ESIw). It is also noteworthy that no additional photosensitizer
was needed for the reaction of the DOPs leading to the
bislactones. The transformation happened smoothly upon
irradiation of O2-saturated acetonitrile solution containing
2a or 4a with light of wavelength longer than 400 nm or 300 nm
respectively. UV absorption of 2a in O2-saturated acetonitrile
solution indicated the formation of ground state CTC (ESIw).15
Thus electron transfer upon the excitation of the ground state
CTC to generate superoxide radical anions could be the initial
step for the transformation of 2a into 3a.
Since the DOPs with the dioxine moiety are good substrates
for photooxidation leading to bislactones, it is therefore
possible to prepare bislactones using the DOPs generated
in situ as intermediates. One-pot photoreaction using PQ
and styrene as substrates in acetonitrile under an oxygen
atmosphere was found to give the bislactone product 3e with
moderate yield (67%, ESIw). The reaction conditions were
then further optimized. For reactions of PQ and alkenes,
change of solvent from benzene to acetonitrile upon complete
conversion of PQ and before further irradiation of the reaction
mixture under an oxygen atmosphere was found to be very
useful to get the bislactone products with higher yields. Under
the optimized reaction conditions, the yield of 3e could be as
high as 88% as shown in Table 3.
Results of the sequential reactions of PQ or PN with aryl
substituted alkenes 1e–1j as well as with the 3,4,6-tri-O-acetyl-
D-glucal (1h) under optimized conditions are shown in Table 3.
All the reactions proceeded smoothly to give the bislactones with
moderate to good yields and variable diastereoselectivities. The
major diastereoisomer in the final biphenyl or bipyridine-fused
bislactone products was with the relative configuration of
(aR, R) as shown in the crystal structure of 5e (ESIw).
Electron withdrawing groups on the phenyl ring of styrene
seemed to impede the formation of corresponding bislactone
products (entries 4 and 5). Double substitution on the CQC
bond either at one end or two ends showed a neglectable effect
on the transformations (entries 6 and 7). It is noteworthy that
reaction of PQ with (E)-prop-1-en-1-ylbenzene 1j and (Z)-
prop-1-en-1-ylbenzene 1k both gave 3j with the relative
configuration of (aR, R, R) (ESIw) as the predominant product.
The bislactone product 3l with a framework similar to the core
of the ellagitannin family has also been prepared through
the sequential reaction of PQ with 3,4,6-tri-O-acetyl-D-glucal
(entry 9). A pair of diastereoisomers with a relative ratio
around 1 : 1 was found in the final product 3k as indicated
The scope of the photooxidation reaction leading to the
bislactones was then explored. As shown in entries 1–5 of
Table 2, the DOPs derived from the photocycloadditions of
PQ or PN with different cycloalkylidenecyclanes (ESIw) could
be photooxidized to give the corresponding bislactones with
yields up to 93%. DOPs obtained from photocycloadditions
of PQ with enol esters or enol ethers (ESIw) could also be
converted into the corresponding bislactones as a mixture of
diastereoisomers with the relative configuration of (aR, R) and
(aR, S) respectively (entries 6–8 in Table 2). The diastereo-
isomers could be distinguished by different chemical shifts in
1H NMR and the diastereoselectivity shown in Table 2 was thus
1
determined by the H NMR of the crude products. The major
diastereoisomer was found to be with the relative configuration
of (aR, R) according to the X-ray crystal structure of the major
isomer in 7 (ESIw). The 2-methylphenanthro[9,10-d][1,3]dioxole
12 could also be photooxidized under the same conditions to give
the biphenyl-fused nine-membered lactone 13 (Table 2, entry 9).
1
by H NMR.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 1168–1170 1169

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Table 3 Sequential photoreactions and photooxidations of PQ or
PN with aryl substituted alkenes
(No. 2011CB935800), National Natural Science Foundation
of China (20972067, 90813035) and the Program for New
Century Excellent Talents in University (NCET-08-0271).
HKF would like to thank the Malaysian Government and
Universiti Sains Malaysia for the Research University Grant
No. 1001/PFIZIK/811160.
Entry
Substrates
Products and yieldsa
d.r.b
1
14 : 1
Notes and references
2c
9 : 1
9 : 1
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a
b
Isolated yield. d.r. based on 1H NMR of the crude products.
c
Irradiation with 4300 nm light in acetonitrile.
In summary, we have presented a novel method to construct
biaryl containing medium-ring bislactones starting from the readily
available 9,10-phenanthrenedione or 1,10-phenanthroline-
5,6-dione and various alkenes. This photocycloaddition/
photooxidation approach to the biaryl containing lactones
was both facile and highly atom-efficient. Various biaryl fused
lactones could be obtained by this method, including those with
a similar framework to the ellagitannin family and the bipyridine
fused lactones which could be useful ligands for novel metal-
complex catalysts. Further investigation on the reaction
mechanism and the synthetic applications of the methods is
now underway.
The authors would like to acknowledge financial support
from the National Basic Research Program of China
c
1170 Chem. Commun., 2012, 48, 1168–1170
This journal is The Royal Society of Chemistry 2012