Synthesis of multiply substituted polycyclic aromatic hydrocarbons by iridium-catalyzed annulation of ring-fused benzocyclobutenol with alkyne through C-C bond cleavage

Article abstract of DOI:10.1002/anie.201509973

The first iridium-catalyzed intermolecular cyclization between alkynes and ring-fused benzocyclobutenols (RBCB) through C-C bond cleavage is described. A variety of elusive polycyclic aromatic hydrocarbons (PAHs) with multiple substituents are obtained in good yields under mild conditions. This procedure provides a unique and expeditious tool for the synthesis of PAHs. Expanding the family: The iridium-catalyzed intermolecular cyclization between ring-fused benzocyclobutenols and alkynes through C-C bond cleavage is described. A variety of elusive polycyclic aromatic hydrocarbons (PAHs) with multiple substituents are obtained in good yields under mild conditions. The transformation exhibits good functional-group tolerance and regioselectivity.

Full text of DOI:10.1002/anie.201509973

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International Edition: DOI: 10.1002/anie.201509973
German Edition: DOI: 10.1002/ange.201509973
Polycyclic Aromatic Hydrocarbons
Synthesis of Multiply Substituted Polycyclic Aromatic Hydrocarbons
by Iridium-Catalyzed Annulation of Ring-Fused Benzocyclobutenol
À
with Alkyne through C C Bond Cleavage
Jiajia Yu+, Hong Yan+, and Chen Zhu*
Abstract: The first iridium-catalyzed intermolecular cycliza-
tion between alkynes and ring-fused benzocyclobutenols
methods. Therefore, the development of a convenient inter-
molecular approach to highly substituted angular PAHs
remains challenging and is of great significance for multiple
fields of chemistry, pharmaceuticals, and material sciences.
Benzocyclobutenols (BCB) are frequently employed as
privileged building blocks for the construction of complex
cyclic molecules and natural products.[7,8] Recently, Murakami
et al. and Wang et al. reported the rhodium-catalyzed cycli-
zation of BCB with alkynes or diazo esters, respectively.[7b,e]
However, the reactions required high temperature (1008C),
the utility of products was not fully demonstrated, and most
importantly, the preparation of BCB usually requires tedious
synthetic routes.[9] We are interested in ring-fused benzocy-
clobutenols (RBCB) as they can be easily obtained using
a one-step synthesis from commercially available aryl bro-
mides and cyclic ketones.[10] In particular, the presence of
additional rings provide a platform suitable for further
À
(RBCB) through C C bond cleavage is described. A variety
of elusive polycyclic aromatic hydrocarbons (PAHs) with
multiple substituents are obtained in good yields under mild
conditions. This procedure provides a unique and expeditious
tool for the synthesis of PAHs.
P
olycyclic aromatic hydrocarbons (PAH) with extended p-
conjugated systems have attracted immense interest because
of their broad application in organic, optical, and electronic
materials.[1] Generally, the properties and stability of PAHs
depend heavily on their structural features.[2] For examples,
angular PAHs with arm-chair peripheries are more stable
than linear PAHs with zig-zag peripheries when exposed to
light and air (Figure 1).[3] As a result, angular PAHs are
À
aromatization (Scheme 1, top). The benzocyclobutyl C C
bond can be cleaved in “distal” or “proximal” pathway.[7,11,12]
We recently reported the silver- or manganese-catalyzed
Figure 1. Linear and angular PAHs with different stabilities.
commonly considered as promisingly practical organic mate-
rials.[4] On the other hand, many compounds based on angular
PAHs such as phenanthrene have exhibited remarkable
pharmacological activities.[5] Currently, the common synthetic
methods for the preparation of PAHs employ intramolecular
cyclization,[6] in which the substrate scope and product
diversity are quite limited as a result of the use of precursor
compounds which themselves require multi-step preparative
[*] J. Yu,[+] H. Yan,[+] Prof. Dr. C. Zhu
Key Laboratory of Organic Synthesis of Jiangsu Province
College of Chemistry, Chemical Engineering and Materials Science
Soochow University
199 Ren-Ai Road, Suzhou, Jiangsu 215123 (China)
E-mail: chzhu@suda.edu.cn
Prof. Dr. C. Zhu
Key Laboratory of Synthetic Chemistry of Natural Substances
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
345 Lingling Road, Shanghai 200032 (China)
[+] These authors contributed equally to this work.
À
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201509973.
Scheme 1. C C cleavage of RBCB and its applications in the synthesis
of a diverse range of angular PAHs.
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À
distal C C bond cleavage of RBCB to generate medium-sized
carbocyclic fluorides or azides (Scheme 1, path (a)).[13]
Inspired by these findings, it is conceivable that the cyclization
À
of alkyne with RBCB by means of proximal C C cleavage
might lead to polyaromatic compounds. Herein, we disclose
the first iridium-catalyzed annulation of RBCB with alkynes
to efficiently produce a variety of multiply substituted PAHs
À
in good yields (Scheme 1, path (b)). The proximal C C bond
is regioselectively cleaved under mild conditions, mostly at
room temperature.
Our investigation of the annulation reaction commenced
with the examination of reaction parameters, including
catalysts and solvents. The use of many transition-
metal catalysts (for example, Pd(OAc)2, [Rh(PPh3)3Cl],
[{Rh(COD)Cl}2], [{RhCp*Cl2}2], and [{Ru(cymene)Cl2}2];
COD = 1,5-cyclooctadiene, Cp* = pentamethylcyclopenta-
dienyl) failed to give the expected product. To our delight,
[{Rh(OH)(COD)}2] and [{Ir(OMe)(COD)}2] enabled the
reaction, with the iridium catalyst giving a higher yield than
the rhodium catalyst at room temperature. Among the
organic solvents screened, toluene delivered the best yields.
After considerable efforts, the optimized reaction conditions
were defined and subsequently employed for the evaluation
of substrate scope (Scheme 2). Initially, a variety of alkynes
were tested, showing good functional-group tolerance for the
reaction conditions. Generally, the electron-rich alkynes
provided better yields than electron-poor ones (3a–c versus
3d). Halogenated alkynes (F, Cl, and Br) exhibited remark-
able performance in the annulation reaction (3e–g). In
particular, the presence of the bromide in 3g provides
opportunity for later functionalization of the molecule
through cross-coupling reactions. The reaction afforded
CF3-containing polycyclic product 3h in excellent yield.
Interestingly, in the cases of ortho-substituted diarylalkyne,
a couple of isomers were generated in 1:1 ratio and could be
separated by column chromatography on silica gel (3i). In
addition to aryl alkynes, heteroaryl and alkyl alkynes were
also suitable substrates to furnish the corresponding adducts
in synthetically useful yields (3j–m). Notably, only a single
regioisomer was obtained when unsymmetric alkyne was
applied (3m), indicating an exclusive regioselectivity. After
completing our assessment of functional-group tolerance, we
set about investigating the generality of the RBCB unit by
varying its framework. The presence of either aryl or alkyl
group on the ring did not compromise the high yields (3n–p).
Aside from the six-membered ring-fused BCB, the five, seven,
and eight-membered ring-fused substrates could also readily
generate the products 3q–s, although elevated temperatures
were required. This result is particularly useful as these
products are otherwise difficult to prepare. Significantly, the
addition of an extra ring system to RBCB could easily
increase the product complexity, giving rise to the desired
polycyclic compounds in satisfactory yields (3t–y).
Scheme 2. Substrate scope for the annulation reaction of RBCB with
alkynes. Conditions: 1 (0.20 mmol), 2 (0.22 mmol), [{Ir(OMe)(COD)}2]
(0.005 mmol, 2.5 mol %), toluene (2.0 mL), RT, then treatment with
TFA (0.10 mmol, 0.5 equiv) for 1 h. Yields of isolated products given.
[a] TFA (9.0 equiv). [b] 1108C. [c] 708C.
With a diverse range of polycyclic precursors in hand, we
then embarked on their transformation into PAHs. The
aromatization occurred smoothly in the presence of 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) at room tem-
PAHs (Scheme 3). Both electron-rich and electron-deficient
substrates gave rise to the expected products in good yields
(4a–e). Susceptible functional groups, such as acetyl and
perature.
A variety of representative molecules from
Scheme 2 were selected and converted into the corresponding
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Scheme 4. Synthesis of dibenzo[g,p]chrysene. MsOH=methane-
sulfonic acid, DCM=dichloromethane.
Figure 2. Proposed reaction mechanism.
Scheme 3. Preparation of angular PAHs. Conditions: 3 (0.20 mmol)
and DDQ (0.60 mmol, 3.0 equiv) in CH2Cl2 (2.0 mL) at RT. Yields of
isolated products are given. [a] DDQ (4.0 equiv).
1 generated the iridium oxide a. Simultaneously, the b-carbon
elimination of a occurred, forming the aryl–iridium species b.
The subsequent insertion of alkynyl and carbonyl units led to
the cyclized intermediate, iridium complex d. The protonation
of d by 1 regenerated intermediate a and meanwhile released
the tertiary alcohol e, which further reacted to form 3 by
means of acid-promoted dehydration. Compound 3 could be
further aromatized to PAH 4 by DDQ oxidation.
bromo, remained intact under the oxidative conditions (4d,
4 f). Similar to its precursor 3i, compound 4g was also
generated in the form of isomers with d.r. = 1:1, which were
separable by column chromatography. Heteroaryl and alkyl
substituents were also tolerated (4h–k). In addition to
phenanthrenes 4a–l, several elusive PAHs containing four-
to six-fused aromatic rings were also readily prepared in high
yields (chrysene (4m), benzo[c]phenanthrene (4n), benzo-
[g]chrysene (4o), benzo[f]picene (4p), and dibenzo-
[c,g]chrysene (4q)). Chrysene 4m could be obtained from
either 3t or 3u in comparable yields. It can be anticipated that
additional different types of complex PAHs can be accessed
by the simple manipulation of RBCB skeletons.
The utility of this method was further demonstrated by the
transformation of the obtained PAHs into dibenzo-
[g,p]chrysene, a twisted PAH for the preparation of non-
linear-optical and liquid-crystalline materials.[14] For example,
4b was readily converted into 5 in 82% yield at room
temperature (Scheme 4).[15]
In summary, we have developed the first iridium-cata-
lyzed intermolecular cyclization between alkynes and ring-
À
fused benzocyclobutenols through C C bond cleavage. The
transformation exhibits good functional-group tolerance and
unique regioselectivity. A variety of elusive polycyclic aro-
matic hydrocarbons with multiple substituents are synthe-
sized in good yields under mild reaction conditions. This
procedure provides a conceptually new and expeditious
approach for the synthesis of angular PAH derivatives.
Acknowledgements
C.Z. is grateful for financial support from Soochow Univer-
sity, the National Natural Science Foundation of China
(21402134), the Natural Science Foundation of Jiangsu
The proposed reaction mechanism is outlined in Figure 2.
Initially, the incorporation of the iridium catalyst and RBCB
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À
Keywords: annulation · C C cleavage reactions ·
homogeneous catalysis · iridium ·
polycyclic aromatic hydrocarbons
How to cite: Angew. Chem. Int. Ed. 2016, 55, 1143–1146
Angew. Chem. 2016, 128, 1155–1158
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Received: October 26, 2015
Published online: December 3, 2015
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