Polyphosphoric acid promoted synthesis of 10,11-dihydrobenzo[j]fluoranthen- 12-one

Article abstract of DOI:10.1021/ol3006979

A straightforward synthesis of 3,8-dimethoxy-10,11-dihydrobenzo[j] fluoranthen-12-ones 1 is reported in a seven-step route from biphenyl-4,4′-diol 2 via the transformation of a double Claisen rearrangement, cross metathesis with ethyl acrylate, and polyph

Full text of DOI:10.1021/ol3006979

ORGANIC
LETTERS
2012
Vol. 14, No. 9
2198–2201
Polyphosphoric Acid Promoted Synthesis
of 10,11-Dihydrobenzo[ j]fluoranthen-12-one
Meng-Yang Chang,* Tein-Wei Lee, and Ming-Hao Wu
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University,
Kaohsiung 807, Taiwan
mychang@kmu.edu.tw
Received February 6, 2012
ABSTRACT
A straightforward synthesis of 3,8-dimethoxy-10,11-dihydrobenzo[j]fluoranthen-12-ones 1 is reported in a seven-step route from biphenyl-4,40-
diol 2 via the transformation of a double Claisen rearrangement, cross metathesis with ethyl acrylate, and polyphosphoric acid (PPA)-promoted
FriedelꢀCrafts electrophilic benzannulation in good yields.
The fluoranthene carbon skeleton with the indeno-
annelated polycyclic aromatic hydrocarbons (PAHs) is
prevalent in different areas of chemistry, including natural
products,1 organic electronics as well as sensing,2 and
related synthetic or medical applications.3 There are a
number of processes available to generate the structural
skeleton of fluoranthenes, but generally, they are syn-
thesized by a transition-metal-mediated cascade arylꢀ
aryl coupling reaction4 and flash vacuum pyrolysis of
benzannulated materials.5 Some natural products with the
polyoxygenated reduced benzo[j]fluoranthene framework,
such as refescine,1a dalesconol A,1b daldinone B,1c daldi-
none C,1d and hypoxylonol F1e were isolated from various
species with unique biological activities as shown in Figure 1.
In this paper, we present a novel synthesis of dimethoxy
dihydrobenzo[j]fluoranthenone skeleton 1 with the core
structure of natural products via polyphosphoric acid
(PPA)-promoted intramolecular double FriedelꢀCrafts
electrophilic benzannulation.6 The one-pot and expedi-
tious cascade-type cyclization forms three of the five rings
in the benzo[j]fluoranthene system.
(1) (a) Menachery, M. D.; Muthler, C. D.; Buck, K. T. J. Nat. Prod.
1987, 50, 726. (b) Zhang, Y. L.; Zhang, J.; Jiang, N.; Lu, Y. H.; Wang, L.;
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2006, 106, 4843.
The overall process involved three transformations
of double Claisen rearrangement, cross metathesis, and
FriedelꢀCrafts electrophilic benzannulation as shown in
Scheme1. Initially, doubleO-allylationof starting material
2 with the combination of K2CO3 and allyl bromide
(5) (a) Amick, A. W.; Wakamiya, A.; Scott, L. T. J. Org. Chem. 2008,
73, 5119. (b) Peng, L.; Scott, L. T. J. Am. Chem. Soc. 2005, 127, 16518.
(6) For reviews on the intramolecular FriedelꢀCrafts reaction, see:
(a) Heaney, H. InComprehensive Organic Synthesis;Trost, B. M., Fleming, I.,
Eds.; Pergamon Press: Oxford, 1991; Vol. 2, pp 733 and 753. (b) Thasana,
N.; Pisutjaroenpong, S.; Ruchirawat, S. Synlett 2011, 1080. (c) Romaine,
I. M.; Hempel, J. E.; Shanmugam, G.; Hori, H.; Igarashi, Y.; Polavarapu,
P. L.; Sulikowski, G. A. Org. Lett. 2011, 13, 4538.
(3) For reviews on the polycyclic aromatic hydrocarbons, see: (a)
Kotha, S.; Misra, S.; Halder, S. Tetrahedron2008, 64, 10775. (b) Scott, L.
Pure Appl. Chem. 1996, 68, 291. (c) Rabideau, P. W.; Aygula, A. Acc.
Chem. Res. 1996, 29, 215. (d) Buchl, M.; Hirsch, A. Chem. Rev. 2001,
101, 1153.
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Quimby, J. M.; Scott, L. T. Adv. Synth. Catal. 2009, 351, 1009. (c)
Wegner, H. A.; Scott, L. T.; de Meijere, A. J. Org. Chem. 2003, 68, 883.
(d) Dang, H.; Levitus, M.; Garcia-Garibay, M. A. J. Am. Chem. Soc.
2002, 124, 136.
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Chem. Rev. 2004, 104, 2939. (b) Nubbemeyer, U. Synthesis 2003, 961. (c)
Hiersemann, M.; Abraham, L. Eur. J. Org. Chem. 2002, 1461. (d) Chai,
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r
10.1021/ol3006979
Published on Web 04/19/2012
2012 American Chemical Society

Scheme 1. Synthesis of Dihydrobenzo[ j ]fluoranthen-12-ones 1
without the formation of side products. By adjusting the
heating time, 4a could be obtained as the sole product. The
treatment of 4a with hydrogen in the presence of 10%
palladium on activated carbon in ethyl acetate provided
another substrate, 2a, with two n-propyl groups on the C3
and C30 positions of the biphenyl-4,40-diol skeleton, in a
99% yield. Next, O-methylation of 4a with K2CO3 and
methyl iodide yielded 5a in a 95% yield.
Based on the successful results, treatment of 4a with
Grubbs second generation catalyst and ethyl acrylate
produced a mixture of (E,E)-, (E,Z)-, and (Z,Z)-R,β-
unsaturated esters in 1,2-dichloroethane in reflux tem-
perature for 10 h.8 The ratios of mixed products were
not determined by 1H NMR spectra. Without purifica-
tion, hydrogenation of the mixed products yielded 6a
in a 70% yield in two steps. Finally, 3,8-dimethoxy-
10,11-dihydrobenzo[j]fluoranthen-12-one 1a could be
(8) For the cross metathesis reaction with acrylate, see: (a) Formann,
G. S.; Tooze, R. P. J. Organomet. Chem. 2005, 690, 5863. (b) Chartterjee,
A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc.
2003, 125, 11360. (c) Abbas, M.; Slugovc, C. Tetrahedron Lett. 2011, 52,
2560. (d) Rybak, A.; Meier, M. A. R. Green Chem. 2007, 9, 1356. (e)
Kirschning, A.; Harmrolfs, K.; Menneche, K.; Messinger, J.; Schon, U.;
Grela, K. Tetrahedron Lett. 2008, 49, 3019. (f) Cossy, J.; Bargiggia, F. C.;
BouzBouz, S. Tetrahedron Lett. 2002, 43, 6715.
Figure 1. Structural frameworks of refescine, dalesconol A,
daldinone B, daldinone C, hypoxylonol F, and skeleton 1.
(9) The representative procedure and spectral analysis of 1 were
described in the Supporting Information. The b and d series of 4ꢀ6
should be formed as the mixtures of diastereomers. However, the related
resolutions of the meso and DL isomers had been not observed from the
NMR spectrum. Perhaps the given distance between the stereocenters
was so long that the free rotation of bonds in between was easily
generated.
afforded 3a in a 98% yield. After reaction under Claisen
conditions of 180ꢀ200 °C in decalin for 8 h,7 4a was
isolated in a 89% yield. Notably, when the reaction time
was changed to 2 h, or 6 h, the ratio value of mono- and
direarranged compounds was isolated in a 3/1 or 1/3 ratio
Org. Lett., Vol. 14, No. 9, 2012
2199

synthesized by the basic hydrolysis of 6a, followed by
treatment of the resulting bis-acid 7a with PPA.
under a number of reaction conditions because complex
mixtures of products were isolated); (iii) the O-methylation
of bis-phenol 4 with K2CO3 and methyl iodide in acetone
at reflux for 5 h; (iv) cross metathesis of bis-olefin 5
with ethyl acrylate in 1,2-dichloroethane at reflux for 10 h,
followed by hydrogenation of the resulting R,β-unsaturated
ester; (v) basic hydrolysis of bis-ester 6, followed by
PPA-mediated benzannulation of the resulting 7. Thus,
five products, 1aꢀ1e, with the core skeleton of benzo-
[ j ]fluoranthene were provided in 66ꢀ75% yields.
Withthese results in hand, conversion of1a to 8 was next
examined. To the best of our knowledge, there are no
literature reports considering the preparation of 8, with a
novel bowl-shaped benzenoid skeleton. When the reaction
time was increased to 40 h, 8 with the fully conjugation-
fused benzene ring was not observed during the PPA-
mediated process.
The formation of the cycloadduct 1a was confirmed
through spectral analysis.9 The 1H NMR spectrum of 1a
exhibited two doublets at δ 8.16 and 6.91 for protons of the
A ring (Scheme 2). The protons of the B ring appeared as
two doublets (δ 9.05 and 7.95) and one doublet of doublets
(δ 7.95). A singlet at δ 7.64 is the proton of the C ring. The
structure of 1a was confirmed by HRMS, which showed a
peak at m/z 331.1340 [Mþ þ 1]. Furthermore, the structural
skeleton of 1a was determined by single-crystal X-ray
crystallography.10
Scheme 2. PPA-Promoted Intramolecular Double Friedelꢀ
Crafts Electrophilic Benzannulation
Under similar conditions, the synthesis of 1f was also
studied, as shown in Scheme 3. Next, the starting material
2b was prepared from 2 in a 66% yield in three steps via
double O-allylation, Claisen rearrangement, and hydro-
genation. By controlling the reflux time (ca. 4 h), the major
monorearrangedproduct wasisolated in 80% yield. Touse
the simple three-step route with O-allylation of 2b (92%),
Claisen rearrangement of 3f (82%), and O-methylation of
4e (93%), the efficient transformation from 2b to 5e could
be performed with a high yield. Furthermore, 1f was
obtained by cross metathesis of 5e, followed by hydro-
genation (79%) and basic hydrolysis of 6e, followed by
PPA-mediated benzannulation (76%). Compound 1g with
the skeleton of 8-aryl-dihydro-1-naphthone was also iso-
lated in 10% yield.11
How is compound 1a produced? As shown in Scheme 2,
the initial event may be considered as the formation of
intermediate I with the skeleton of bis-tetralone from the
PPA-mediated double acylation of 7a. The proposed
intermediate I is symmetrical, except for the proton/
oxocarbenium ion. Intermediate II is afforded from the
methoxy-group-mediated bond migration, followed by the
cascade-type ring closure on the skeleton of intermediate I.
The five-membered ring of intermediate II is generated,
and the benzo[j]fluoranthene is established from the bi-
phenyl skeleton. After hydrogen abstraction of intermedi-
ate II and dehydration of the resulting intermediate III,
sequential oxidative dehydrogenation affords 1a.
Scheme 3. Synthesis of Compound 1f
From the above-mentionedexperiment, otheranalogues
1 could be prepared from skeleton 2. The target skeleton 1
was prepared using the five-step protocol, described as
follows: (i) the O-allylation of bis-phenol 2 (R = H, n-Pr;
R1 = H, Me, Ph) with K2CO3 and bromide (allyl, crotyl,
cinnamyl) in acetone at reflux for 5 h; (ii) double Claisen
rearrangement of skeleton 3 in decalin at reflux for 10 h
(however, attempts to rearrange 3e were unsuccessful
To extend this methodology to the preparation of 8,
diketone 9 was chosen as the precursor. It was prepared in
87% yield by the reaction of bis-acid 7a with thionyl
(10) The crystal structure of 1a has been deposited in CCDC with
number 860695. Compound 1a crystallizes in the triclinic crystal system,
˚
˚
˚
space group P1, a = 8.0012(9) A, b = 9.2072(10) A, c = 11.4227(13) A,
3
V = 776.07(15) A , Z = 2, Dcalcd = 1.414 g/cm3, F(000) = 348, 2θ range
(11) By increasing the heating time, the conversion of 1g to 1f could
be accomplished.
˚
1.86°ꢀ26.55°, R indices (all data) R1 = 0.0533, wR2 = 0.0997.
2200
Org. Lett., Vol. 14, No. 9, 2012

methylation of 9 with excess Grignard reagent via an
intermediate with the magnesium complex. However, no
formation of 8 was observed for the PPA-mediated
reaction of 10a. In another case, O-allylation of 10a
with excess sodium hydride and allyl bromide yielded
11a and 11b with a ratio value of 7/1 at reflux in good
yields. In particular, enol ether (E)-11b was isolated in
10% yield via the base-mediated double migration of
11a. The results suggested that the steric configuration
might cause mono-O-alkylation and olefinic migration.
The structural framework of 11a was determined by
single-crystal X-ray crystallography.13 X-ray diffraction
analysis could be obtained to prove the constitution and
relative configuration.
Scheme 4. Reaction of Compound 9
In summary, we have successfully presented a synthetic
methodology for the skeleton of 3,8-dimethoxy-10,11-
dihydrobenzo[j]fluoranthen-12-ones 1, which involved
PPA-mediated double FriedelꢀCrafts electrophilic cycli-
zation, followed by a benzannulation. The novel strategy
showed that PPA is an excellent acid with which to
promote the formation of the core structure of natural
products with the fluoranthene carbon skeleton. Consider-
ing the utility of these polycyclic aromatic compounds, the
development of these general synthetic approaches is
significant.
chloride, followed by aluminum chloride during a double
intramolecular acylation (Scheme 4). Next, the stereose-
lective NaBH4-mediated double reduction of 9 provided
diol 10a as the sole isomer in a 90% yield via the possible
boron complex chelated intermediate.12 Furthermore,
only 10b was also generated in 77% yield by double
Acknowledgment. The authors would like to thank the
National Science Council of the Republic of China for its
financial support.
(12) (a) de Vries, T. S.; Majumder, S.; Sandelin, A. M.; Wang, G.;
Vedejs, E. Org. Lett. 2012, 14, 688. (b) Shapland, P.; Vedejs, E. J. Org.
Chem. 2004, 69, 4094.
Supporting Information Available. Experimental data
1
and scanned photocopies of H and 13C NMR spectral
(13) CCDC 860773 (11a) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12
Union Road, Cambridge CB2 1EZ, UK; Fax: 44-1223-336033; E-mail:
deposit@ccdc.cam.ac.uk).
data are provided. This material is available free of charge
via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
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