Intramolecular cascade hydroarylation/cycloisomerization strategy for the synthesis of polycyclic aromatic and heteroaromatic systems

Article abstract of DOI:10.1002/ejoc.201201329

A new PtCl₂/PtCl₄-catalyzed hydroarylation/ cycloisomerization cascade reaction leading to the formation of two aromatic or heteroaromatic rings in one step is reported. The strategy developed is exemplified by the synthesis of the 5

Full text of DOI:10.1002/ejoc.201201329

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201201329
Intramolecular Cascade Hydroarylation/Cycloisomerization Strategy for the
Synthesis of Polycyclic Aromatic and Heteroaromatic Systems
[a]
[a]
[a]
[a]
[a]
ˇ
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Jan Storch,* Martin Bernard, Jan Sýkora, Jindrich Karban, and Jan Cermák
Keywords: Fused-ring systems / Platinum / Helical structures / Heterocycles
A new PtCl2/PtCl4-catalyzed hydroarylation/cycloisomeriza-
tion cascade reaction leading to the formation of two aro-
matic or heteroaromatic rings in one step is reported. The
strategy developed is exemplified by the synthesis of the 5,6-
dihydrobenzo[c]phenanthrene and 6H-naphtho[2,1-c]chrom-
ene skeletons. Attempts to prepare [8]helicene-like mole-
cules are also discussed.
organic synthesis from the viewpoint of operational sim-
plicity and assembly efficiency. This work is focused on syn-
thetic investigations of proposed cascade reactions and their
viability to build helical backbones. Our retrosynthetic
strategy outlined in Scheme 1 is based on simple disconnec-
tion of the C7–C7a bond in I to form 1,5-enyne II. A sec-
ond disconnection is made at the C1–C1a bond to give cor-
responding diyne III. In the direction of synthesis, the first
transformation step would be a hydroarylation reaction to
yield 2H-chromene and 1,2-dihydronaphthalene derivatives.
Further transformation in the cascade sequence would in-
volve cycloisomerization to afford the target molecules.
Introduction
Over the past few years, significant research has been di-
rected toward the development of new methodologies for
synthetic efficiency and atom economic processes. Transi-
tion-metal-catalyzed enyne cycloisomerization is one of the
most important strategies used to form functionalized cyclic
structures.[1] Among several transition metals, the use of
platinum(II,IV)-based catalysts has many advantages. The
reactions tend to be operationally safe, simple, and practical
to perform, and they also do not generally require rigor-
ously inert conditions. PtII,IV chlorides are able to catalyze
a broad range of C–C bond-forming reactions that allow
enynes and related substrates to be converted into signifi-
cantly increased, structurally complex carbo- and heterocy-
clic products.[2] Recently, we have shown that the double
PtCl2-catalyzed intramolecular hydroarylation of biphenylyl
naphthalenes bearing an alkyne unit in the ortho position
leads to the formation of carbo- and hetero[6]helicene back-
bones.[3] As part of our ongoing interest in the synthesis of
helicenes and helicene-like molecules, we now report the
way to 6H-naphtho[2,1-c]chromene and 5,6-dihy-
drobenzo[c]phenanthrene derivatives and attempts to pre-
pare [8]helicene-like molecules through intramolecular
Scheme 1. Retrosynthesis.
To probe the viability and outcome of the envisaged cy-
cloisomerization process, suitable model compounds were
prepared (Scheme 2). (4-Iodo-1-butynyl)trimethylsilane[4]
was converted into the zinc reagent[5] and treated with iodo-
benzene under copper(I) iodide mediated Negishi coupling
conditions to afford 1b after deprotection with tetrabut-
ylammonium fluoride (TBAF). Sonogashira coupling with
[(2-iodophenyl)ethynyl]trimethylsilane[6] and 1-iodo-2-(prop-
ynyl)benzene prepared from 1-bromo-2-(propynyl)benz-
ene[3b] afforded diynes 2a and 2c. Subsequent deprotection
of the trimethylsilyl (TMS) group gave diyne 2b. To achieve
the desired intramolecular hydroarylation/cycloisomeriza-
tion cascade and, accordingly, to build the benzo[c]phen-
anthrene skeleton, diyne 2b was exposed to a catalytic mix-
ture of PtCl2/PtCl4 in toluene at 90 °C overnight. Product
PtCl2/PtCl4-catalyzed
cascade reactions.
hydroarylation/cycloisomerization
Results and Discussion
The development of cascade reactions for the efficient
construction of complex molecules is an important goal in
[a] Institute of Chemical Process Fundamentals of the ASCR,
Rozvojova 2/135, 16502 Prague 6 – Suchdol, Czech Republic
Fax: +420-220-920661
E-mail: storchj@icpf.cas.cz
Homepage: www.icpf.cas.cz
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201329.
260
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 260–263

Synthesis of Polycyclic Aromatic and Heteroaromatic Systems
Scheme 2. Model synthesis of 5,6-dihydrobenzo[c]phenanthrene.
3 was isolated in 67% yield. Unfortunately, propyne deriva- chiroptical and electro-optical functional materials.[9] Our
tive 2c did not afford the desired product under similar con- attempts to prepare these products required tetraynes 7b
ditions. Changing the solvent from nonpolar toluene to po- (Scheme 4) and 10b (Scheme 5) as precursors.
lar acetonitrile also failed; the reaction at 80 °C provided a
complex mixture with trace amounts of the desired product
(analyzed by GC–MS). The use of harsher conditions
(180 °C, toluene or acetonitrile, MW) also did not work.
To explore the scope of this approach, we decided to syn-
thesize heteroanalogues 2e and 2f. Propargyl phenyl ether[7]
was transformed into the diynes by simple steps in good
yields (Scheme 3).
Scheme 4. Synthesis of tetrayne 7b.
Scheme 3. Model synthesis of 6H-naphtho[2,1-c]chromene.
Intramolecular hydroarylation/cycloisomerization in-
duced by PtCl2/PtCl4 proved to be effective, and 6H-
naphtho[2,1-c]chromene 4a was obtained in 65% yield. In
the case of 2f, toluene as a reaction medium did not prove
to be the solvent of choice. The use of acetonitrile as a
commonly used polar solvent for enyne cycloisomerizations
was ineffective at 80 °C, and only at higher temperatures
(180 °C, 30 min, MW) was 4b repeatedly obtained in 40%
yield.
Scheme 5. Synthesis of tetrayne 10b.
Copper(I) iodide assisted coupling of 5, prepared from
3,6-dibromonaphthalene-2,7-diol,[10] with a zinc reagent
After screening the cascade reaction we set out to at- gave diyne 6. Sonogashira coupling of 6b with [(2-iodo-
tempt a similar process for the preparation of [8]helicene- phenyl)ethynyl]trimethylsilane provided desired tetrayne 7b.
like molecules. Among π-conjugated molecules, helicenes, Synthesis of the dioxa analogue started from commercially
which consist of ortho-annulated aromatic rings,[8] have at- available naphthalene-2,7-diol, which was treated with pro-
tracted much attention because of their inherent chirality, pargyl bromide to give bis-ether 9. Its conversion into 10b
and this has recently led to promising applications in asym- was achieved under the same conditions as those used to
metric catalysis, enantioselective molecular recognition, and prepare the carbo analogue.
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ˇ
J. Storch, M. Bernard, J. Sýkora, J. Karban, J. Cermák
SHORT COMMUNICATION
Having prepared the suitable building block, we could rings in one step. Fused aromatic systems can be prepared
approach the hydroarylation/cycloisomerization experi- readily in moderate yields from simple diyne precursors. To
ments. Cycloisomerization of 7b with the mixed PtCl2/PtCl4 the best of our knowledge, this is the first example of a one-
catalyst proved to be the proper choice. The best results pot cascade reaction comprising two diverse cycloisomer-
were obtained with a catalyst loading of 20 mol-% each, but ization transformations. The need for a Pt2+/Pt4+ system
the yield did not exceed 20%. Other catalysts that were arises from the presence of two different alkyne bonds. For
tested (Table 1) provided only starting material or complex the reaction to be successful there has to be a coordination
reaction mixtures, and in no case was there any detectable step of a Ptn+ species to the alkyne bond to give I and II
formation of the desired product.
(Scheme 7). Considering the fact that both triple bonds are
very similar in nature, we can assume that the Pt salts might
coordinate equally well to both alkynes, and thus, I and II
will be in equilibrium throughout the reaction, although
only I enables the hydroarylation step. Enyne III then un-
dergoes a second Ptn+ coordination to give IV. If there are
electronic influences (alkyne substitution) that would result
in the formation of the more stable form II, the reaction
provides complex mixtures or no conversion. Our ongoing
studies are in progress and are focused on mechanistic con-
siderations.
Table 1. Catalytic experiments for 7b.
Entry Catalyst[a]
Solvent
T [°C] Yield [%]
1
2
3
4
5
6
7
8
PtCl2
PtCl4
PtCl2/PtCl4[b]
PtCl2/PtCl4
InCl3
toluene
toluene
acetonitrile
toluene
toluene
toluene
DCM
DCM
DCM
acetonitrile
acetonitrile
90
90
80
90
90
90
r.t.
r.t.
r.t.
60
60
0
0
0
20
0
0
0
0
0
0
0
[b]
AuCl3
AuCl(PPh3)
AuCl(PPh3), AgBF4
AuCl3, PPh3
Hg(OTf)2
9
10
11
Hg(OTf)2·3TMU[c]
[a] Catalyst loading 10 mol-%. [b] PtCl2 (20 mol-%), PtCl4 (20 mol-
%). [c] TMU = tetramethylurea.
Further effort was directed at converting dioxa analogue
10b into dihydrodioxa[8]helicene under the same catalytic
conditions as those used for 7b. We found that a catalyst
loading of 20 mol-% for each species at 90 °C caused com-
plete ether cleavage and afforded only naphthalene-2,7-diol.
A decrease in the catalyst loading to 5 mol-% for each spe-
cies and a decrease in the temperature to 50 °C afforded
oxa[5]helicenol 11 in 60% yield (Scheme 6), but no detect-
able amount of the desired product. Further screening did
not improve the result. The low yield of 8 in comparison to
that of 3 is most likely caused by steric effects, which is in
accordance with the cycloisomerization of 10b.
Scheme 7. Mechanism.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data, and copies of
1
the H NMR and 13C NMR spectra for all products.
Acknowledgments
We appreciate the financial support from the Grant Agency of the
Czech Republic (Grant No. P207/10/1124) and the Technology Ag-
ency of the Czech Republic (Grant No. TA01010646).
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Received: October 8, 2012
Published Online: November 19, 2012
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