Metal-catalyzed annulation reactions for π-conjugated polycycles.

DOI: 10.1002/chem.201304640

Minireview

& Polycyclic Compounds

Metal-Catalyzed Annulation Reactions for p-Conjugated Polycycles Tienan Jin,*[a] Jian Zhao,[a] Naoki Asao,[a] and Yoshinori Yamamoto[a, b]

Chem. Eur. J. 2014, 20, 3554 – 3576

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2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Minireview Abstract: The progress of the metal-catalyzed annulation reactions toward construction of various p-conjugated polycyclic cores with high conjugation extension is described. This article gives a brief overview of various annulation reactions promoted by metal catalysts including C H bond func-

Introduction p-Conjugated polycycles including polycyclic aromatic hydrocarbons (PAHs) and their heterocyclic analogues as well as pconjugated nonaromatic polycycles have been studied intensively in the field of synthetic chemistry and materials science, due to their interesting structural variation, versatile electronic and photophysical properties, varied packing structures, and a wide application in electronic devices[1] As segments of graphite, PAHs comprised of six-membered rings, such as tetracene, pentacene, and their derivatives possess high planarity and rigidity that provide a strong intermolecular p–p interaction with two-dimensional packing modes, exhibiting excellent charge transport ability (Figure 1).[2] Particularly, hexabenzocor-

Figure 1. Representative examples of PAHs and PHAHs.

onene is able to self-assemble into a columnar phase, which further organizes itself to form multiwalled nanotubes.[3] In addition, since the discovery of the remarkable properties of fullerene C60 and its analogues, PAHs containing both five- and [a] Prof. Dr. T. Jin, Dr. J. Zhao, Prof. Dr. N. Asao, Prof. Dr. Y. Yamamoto WPI-Advanced Institute for Materials Research (WPI-AIMR) Tohoku University, 2-1-1, Katahira Aoba-ku, Sendai, 980-8577 (Japan) E-mail: [email protected] [b] Prof. Dr. Y. Yamamoto State Key Laboratory of Fine Chemicals Dalian University of Technology (China) Chem. Eur. J. 2014, 20, 3554 – 3576

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tionalization, [2+2+2] cycloaddition, cascade processes, ring closing metathesis, electrophilic aromatization, and various cross-coupling reactions. A variety of conjugated polycycles with planar, bowl-shaped, and helical structures have been constructed in high efficiency and selectivity.

six-membered rings have attracted considerable attention.[4] For instance, as a fragment of C60, the bowl-shaped corannulene and its derivatives display columnar structures and high quantum yields, which have been also considered as model structures for investigation of the relationships between curvature structure and property. Polycyclic (hetero)aromatic hydrocarbons (PHAHs) are also regarded as an important building blocks in bioactive compounds, photovoltaic materials, and superior semiconductors in field-effect transistors.[1c, 2, 5] For example, in comparison with the acene molecules, heteroacene compounds that contain heteroatoms on the conjugated backbone, such as dinaphthothienothiophene (DNTT) and nitrogencontaining oligoacenes, have a distinct effect on the electronic properties, solubility, and packing arrangements. The impressive structural diversity of those molecules and their potential applications in practical electronic devices led them to receive increasing attention in interdisciplinarity of modern sciences. For these reasons, numerous synthetic methodologies have been developed to construct both known and new p-conjugated polycyclic cores in the past decades.[1] Among them, the most generally used catalyst-free methods include the flash-vacuum pyrolysis (FVP) using high temperature, intramolecular photocyclization reactions, intermolecular Diels–Alder reactions, and intramolecular oxidative cyclodehydrogenation reactions, and so forth. Beside these traditional methods, the synthetic strategy through a metal-catalyzed annulation leads to the construction of p-conjugated polycycles in high chemical yields and high compatibility with a wide range of functional groups.[6] For example, coronene can be achieved in excellent yield, much higher than that of FVP method, by using an ruthenium complex as a catalyst.[7] Furthermore, the metal-catalyzed annulations not only provide an opportunity to create new polycyclic backbones, but also exhibit high regio-, chemo-, and enantioselectivities. For example, nowadays, an enantioselectivity of more than 90 % for helically chiral p-conjugated polycycles was achieved by using transition-metal catalysts combined with chiral ligands.[8] One of the most promising methods is catalytic C H bond functionalization, which has the advantage to form the new C C and C heteroatom bonds directly without pre-functionalization of aromatic C H bonds.[9] In this Minireview, we focus on the illustration of metal-catalyzed annulation reactions toward construction of various pconjugated polycycles with high conjugation extension. The examples described in this paper have been divided into the following categories: 1) C(sp2) H bond functionalization, 2) cascade annulation with alkynes, 3) [2+2+2] cycloaddition, 4) olefin ring-closing-metathesis, 5) electrophilic aromatization,

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Minireview and 6) cross-coupling reactions. The designs of substrate structures and polycyclic cores, various catalyst systems, brief mechanistic discussion, and some applications are described to provide a helpful introduction to reader in this promising research field. Scheme 1. The early studies of Pd-catalyzed intramolecular C H arylation.

C(sp2) H Bond Functionalization Intramolecular C H/C X (X = halogen) coupling reactions The palladium-catalyzed intramolecular C H arylation has been demonstrated as one of the most conceptually useful synthetic methodologies for the construction of PAHS and PHAHs. In 1982, Ames et al. found that the reaction of 3-bromo-4-phenoxycinnoline (1 a) or 3-bromo-4-phenylaminocinnoline (1 b) in the presence of a Pd(OAc)2 catalyst and triethylamine produced benzofuro[3,2-c]cinnoline (2 a) and indolo[3,2-c]cinnoline (2 b) in 19 and 55 %, respectively (Scheme 1).[10] The reaction was extended by Rice et al. for construction of the internal cyclopenta-fused PAHs (CP-PAHs) through an intramolecular coupling of aryltriflates with aromatic C H bonds.[11] The reaction of the triflate of 1-(2-hydroxyphenyl)naphthalene

(3 a) with a [PdCl2(PPh3)2] catalyst in the presence of LiCl and DBU in DMF at 135–140 8C for 6 h produced the corresponding fluoranthene (4 a) in 89 % yield. Comparable yields of benzo[a]fluoranthene (4 b, 84 %), benzo[b]fluoranthene (4 c, 85 %), and indeno[1,2,3-cd]pyrene (4 d, 91 %) were obtained under these reaction conditions (Scheme 2). It is worth noting that this C H arylation exhibited high regiospecificity for the construction of a five- rather than a six-membered ring; for example, treatment of binaphthyltriflate (3 e) under the above Pd-catalyzed conditions afforded the corresponding benzofluoranthene product 4 e in 93 % yield, without formation of the six-membered ring product of perylene. The benzofluorathene product was produced through the formation of a six-membered palla-

Tienan Jin received his Ph.D. in 2004 under the supervision of Prof. Yoshinori Yamamoto at Chemistry Department of Tohoku University (Japan). He then moved to Wayne State University (USA) and worked as a postdoctoral fellow with Prof. J. K. Cha for study of total synthesis of natural products. In 2006, he moved back to Tohoku University and was appointed as an Assistant Professor in the research group of Prof. Y. Yamamoto. Since 2010, he is an Associate Professor in Department of Chemistry and WPI-AIMR at Tohoku University. His research interests mainly focus on development of new transition-metal-catalysis using molecular and nano-structured metal catalysts toward synthesis of polycycles and functional fullerenes. He is also interested in design and synthesis of new p-conjugated polycycles and oligoarenes for application in organic field-effect transistors and photovoltaics.

Naoki Asao received his doctoral degree from Tohoku University in 1992 and became a research associate in Tohoku University immediately. He was appointed lecturer at Hokkaido University in 1995, associate professor at Tohoku University in 2001, and professor at Tohoku University in 2009. He joined Prof. Danheiser group (MIT, USA) as a visiting scientist in 2004. He received the Daicel Chemical Industries Award in Synthetic Organic Chemistry in 1995 and the Chemical Society of Japan Award for Young Chemists in 1997. His current research is focused on the development of nano-structured metallic materials as effective heterogeneous catalysts for molecular transformations. He is also paying attention to the preparation of newly-designed organic semiconductors for organic light emitting field effect transistors.

Jian Zhao was born in Zhangjiagang, China in 1985. He received his B.E. degree in Biological Engineering from Dalian University of Technology in 2007 and his M.S. degree in Chemistry under the direction of Prof. Wei-min Dai and Prof. Jin-long Wu from Zhejiang University in 2010. He began his doctoral study under the mentorships of Prof. Yoshinori Yamamoto supported by IGPAS Program in 2010 and got his Ph.D. degree from Tohoku University in 2013. Then, he is appointed as a Research Associate at WPI-AIMR (Advanced Institute for Materials Research), Tohoku University. His current research interests focus on the development of new transition-metal-catalyzed reactions and their application to organic synthesis.

Yoshinori Yamamoto received Ph.D. degree from Osaka University. In 1977, he was appointed as an Associate Professor at Kyoto University. In 1986, he moved to Tohoku University to take up a position of Professor at Chemistry Department. He was the director of WPI-Advanced Institute for Materials Research in Tohoku University (2007-2012). From 2012, he has been Professor Emeritus of Tohoku University and Executive Research Coordinator at WPI-AIMR. Furthermore, he has been a Professor at the state key laboratory of fine chemicals, Dalian University of Technology (DLUT), in China. He was awarded the Chemical Society of Japan Award (1996), the Humboldt Research Award from Germany (2002), Purple Ribbon Medal from The Cabinet (2006), A. C. Cope Scholar Award from ACS, USA (2007), and Centenary Prize from RSC, UK (2009). In recent years, he is interested in the new molecular transformation using nano-technology and nano-technology using organic synthesis, that is to say, nanoporous metal skeleton catalysts, and dye-sensitized solar cells together with bulk heterojunction solar cells.

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Minireview

Scheme 4. Synthesis of diindenopyrenes by means of C H arylation.

a Pd-catalyzed Suzuki coupling followed by C H arylation in one-pot method (Scheme 5). The tert-butyl-substituted 2-bromobenzeneboronic acid was employed to improve the solubility of the desired products. Although the yields are low, the reactions of tribromopyrene (7 c) and tetrabromopyrene (7 d) Scheme 2. Pd-catalyzed C H arylation for synthesis of CP-PAHs.

dacycle intermediate, which might be much favorable than that of the seven-membered intermediate, while the radical pathway of initial oxidative addition of aryltriflate to Pd catalyst was also considered to be reasonable. Decacyclene core-fused polyarenes, potential starting materials of fullerenes or bowl-shaped polyarenes, were synthesized based on a Pd-catalyzed intramolecular C H arylation of truxene derivatives (5) by the Echavarren group (Scheme 3).[12] The triple C H arylations followed by dehydrogenation of the syntrialkylated truxenes in the presence of a Pd(OAc)2 catalyst, BnMe3NBr, and K2CO3 or Cs2CO3 in DMF at 140 8C afforded the benzo[1,2-e:3,4-e’:5,6-e’’]triacephenanthrylene derivatives (6) in yields of 71 and 40 %. Scott et al. synthesized a new class of PAHs, oligoindenopyrenes, by a Pd-catalyzed C H arylation.[13] The reaction of the isomeric bis(2-bromophenyl)pyrenes (7 a and 7 b) in the presence of a [PdCl2(PPh3)2] catalyst and a DBU base gave two diindenopyrene products 8 a and 8 b in 44 and 53 % yields, respectively (Scheme 4). The triindenopyrene (8 c) and tetraindenopyrene (8 d) compounds were synthesized by means of

Scheme 3. Pd-catalyzed synthesis of decacyclene core-fused polyarenes. Chem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 5. Synthesis of triindenopyrene and tetraindenopyrene by Suzuki coupling/C H arylation in one-pot.

with boronic acid under the Pd-catalyzed optimized conditions are able to produce 8 c and 8 d in 4 and 1 % yields, respectively. These oligoindenopyrenes showed a high thermal stability with intense red colors, which are expected to find use as long wavelength dyes. This one-pot reaction was also applied to the reaction of 1,4-dibromonaphthalene (9) with o-chlorobenzeneboronic acid, affording the desired product, indeno[1,2,3 cd]fluoranthene (10), with cyclopenta-fused rings attached to terminal six-membered rings in quantitative yield, while the use of o-bromobenzeneboronic acid resulted in moderate yield of product (Scheme 6). A similar one-pot methodology by using Kumada coupling followed by C H arylation has been studied by Holmes and Douglas et al.[14] The reaction of 5,6,11,12-tetrachlorotetracene (11) and PhMgBr in the presence of PEPPSI-IPR (3 mol %) produced 9,10-diphenylindeno-

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Scheme 6. One-pot synthesis using 1,4-dibromonaphthalene and o-chlorobenzeneboronic acid.

[1,2,3-fg]tetracene (12) in a high yield of 82 % without obtaining rubrene or the double-annulated diindene product (Scheme 7). The vacuum-deposited heterojunction photovolta-

Scheme 7. Kumada coupling/C H arylation for synthesis of indenotetracene.

ic cell based on the resulting indenotetracene as an electron donor and C60 as an electron acceptor exhibited a power conversion efficiency of 1.5 % with a high open-circuit voltage of 0.955 V. An efficient synthetic method for the preparation of heterocyclic analogues of rubicene was reported by Wudl et al. under the Pd-catalyzed C H arylation (Scheme 8).[15] It was noted that the use of CH3CN as a solvent is crucial for producing a high yield of the corresponding emeradicene 14.

Scheme 8. Pd-catalyzd C H arylation for synthesis of emeradicene.

Due to the high efficiency and selectivity, the Pd-catalyzed C H arylation became a general approach for the construction of the large bowl-shaped complex molecules compared to the traditional FVP method, while the design of the starting substrates is a key for implementation of these transformations efficiently. In 2000, the Scott group succeeded in construction of the bowl-shaped fullerene fragment dibenzo[a,g]corannulene (16) through the intramolecular C H arylation of 7,10-di(2-bromophenyl)fluoranthene (15) using palladacyle or [Pd(PPh3)2Br2] as catalyst combined with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base (Scheme 9a).[16] The reaction proceeded through the formation of a six-membered ring, giving the product in Chem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 9. Pd-catalyzed C H arylation for synthesis of bowl-shaped fullerene fragments.

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Minireview 55–60 % which was higher than that by the FVP method. The five-membered ring formation for construction of as-indaceno[3,2,1,8,7,6-pqrstuv]picenes (18) was reported by Shevlin and Wang.[17] The Me- and MeO-substituted products obtained in high yields with dichlorobenzo[s]picenes (17) as substrates in the presence of [PdCl2(PCy)3] (Cy = cyclohexane; Scheme 9b). This synthetic strategy of the five-membered ring formation was further extended to construct the large curved subunits of C60. Pentaindenocorannulene (20 a) and tetraindenocorannulene (20 b) have been prepared in moderate yields by the Pdcatalyzed five- and fourfold C H arylation reactions under microwave heating conditions using [PdCl2(PCy3)2] as catalyst (Scheme 9c).[18] Steigerwald and Nuckolls et al. reported that under the similar microwave heating conditions, the two- and fourfold annulation reactions of n-dodecyloxy-substituted dichloro- (21 a) and tetrachloro-hexabenzocoronene (21 b) proceeded smoothly to give the soluble PAHs containing two (22 a) and four five-membered rings (22 b) in 35 and 16 % yields, respectively (Scheme 9d).[19] Wu et al. designed starting substrates that are expected to undergo both the five- and sixmembered ring formation in a single molecule through a Pdcatalyzed C H arylation.[20–22] The annulation of trichlorophenanthrene (23 b) in the presence of [PdCl2(PCy3)2] and a mixed bases of DBU and Cs2CO3 afforded the corresponding product, diindeno[1,2,3,4-defg;1’,2’,3’,4’-mnop]chrysene (24 b) in 21 % yield (Scheme 9e).[20] Under similar conditions, cyclization of tetrachlorobenzo[k]fluoranthene (23 a) furnished the desired annulation product 24 a in 31 % yield (Scheme 9e).[21] The sixmembered ring formation method was successfully applied to the synthesis of a bowl-shaped subunit of C70.[22] A buckybowl compound 26 as shown in Scheme 9f was prepared through the Pd-catalyzed fourfold annulation of 7,14-bis(2,6dichlorophenyl)acenaphtho[1,2-k]fluoranthene (25) in a low yield of 10 % due to the low solubility of the product in common organic solvents. The PAHs composed of only six-membered rings, such as dibenzo[fg,op]naphthacene (28), may be obtained through a Pd-cayalyzed C H arylation. The cyclization of the alkoxyfunctionalizd dibromo-1,2,3-triarylbenzene 27 was performed in the presence of a [PdCl2(PPh3)2] catalyst and DBU under heating (Scheme 10).[23] The corresponding double annulation product 28 was obtained in 42 % yield. This new PAH 28 showed a nearly perfect planar structure with a herringbonelike packing arrangement and a remarkably small intermolecu-

Scheme 10. Synthesis of dibenzo[fg,op]naphthacene by a double C H arylation. Chem. Eur. J. 2014, 20, 3554 – 3576

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lar distance, indicating its potential application in organic transistors as an active semiconductor. Most recently, the Nishihara group developed a new synthetic method for picene derivatives by using a Pd-catalyzed intramolecular double C H arylation (Scheme 11).[24] Several functionalized picenes 30 were synthesized in moderate yields by using the corresponding

Scheme 11. Synthesis of picenes, [6]phenacenes, and heteroatom-containing picene-like compound by means of Pd-catalyzed C H arylation.

2,3-bis[(1Z)-2-phenylethenyl]-1,4-dichlorobenzenes 29 as precursors in the catalytic systems of [PdCl2(PhCN)2], PCy3, and pivalic acid (Scheme 11). Under the similar conditions, the reaction of 1-{(Z)-3,6-dichloro-2-[(Z)-styryl]styryl}naphthalenes produced the corresponding [6]phenacenes in good yields. This methodology was applied to the synthesis of phenanthro[1,2b:8,7-b’]dithiophene (30 c), which has been used as a new semiconductor in thin film FETs to show a good hole mobility of 0.1 cm 2 V 1 s 1. The [5]- and [6]helicenes were synthesized by Kamikawa et al. through a Pd-catalyzed C H arylation (Scheme 12).[25] Bis(bromostilbene) (31 a) was chosen as the starting material in the presence of a Pd(OAc)2 catalyst and the air-stable PCy3·HBF4 ligand together with K2CO3 and Ag2CO3, producing [5]helicene (32 a) in 75 % yield. The use of Ag2CO3 is crucial for improving the yield of [5]helicene. Examination of the substitu-

Scheme 12. Synthesis of [5]- and [6]helicenes by means of C H arylation.

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Minireview ent effect on the benzene ring indicated that the present C H arylation is suitable for synthesis of electron-deficient helicenes. Furthermore, this approach can be used to synthesize [6]helicene (32 d) in 30 % yield. A 1,4-palladium shift induced C H arylation has been demonstrated as a powerful synthetic method for preparation of the complex PAHs (Scheme 13).[26] Under the optimized conditions of Pd(OAc)2, diphenylphosphinomethane (dppm), and

Scheme 14. Pd-catalyzed intramolecular C H arylation for synthesis of silicon-bridged biaryls.

Scheme 13. C H arylation through 1,4-palladium migration.

CsOPiv (Piv = pivaloyl) in DMF, 2-iodo-1-phenylnaphthalene (33 a) produced fluoranthene (34 a) in 81 % yield. Mechanistically, the reaction is proposed to proceed through a 1,4-palladium migration from the 2-position of naphthalene to the ortho-position of phenyl substituent, followed by C H arylation at 8-position of naphthalene to afford the desired product. Following this methodology, 9-iodo-10-phenylphenathrene (33 b) was converted to the desired migration product benzene[e]acephenanthrylene (34 b) in 78 % yield. Shimizu and co-workers have reported a novel approach to silicon-bridged biaryl compounds through a Pd-catalyzed intramolecular direct C H arylation of 2-(arylsilyl)aryl triflates (35) (Scheme 14).[27] When 2-[diisopropyl(phenyl)silyl]phenyl triflate (35 a) was treated with Pd(OAc)2/PCy3 and Et2NH in DMAc at 100 8C, the corresponding dibenzosilole 36 a was obtained in high yield. It was noted that the use of organic base Et2NH and bulky isopropyl substituent on silicon is a key for efficient implementation of this transformation.[27a] This method can be applicable for the synthesis of various silicon-bridged thiophene- (36 b), benzothiophene- (36 c), benzofuran- (36 d), indole-fused (36 e) heteroarenes, and helicene-like product 36 f. Among them, the indole-fused silole product 36 e showed a high quantum yield with intense blue emission in the solid state, suggesting its potential application in organic light-emitting diodes (OLEDs). The same group further found that, when 2-[diisopropyl(2-indolyl)silyl]phenyl triflate (37 a) was subjected with a Pd(OAc)2/dppe catalyst system and a large excess of Et2NH, the unexpected 1,2-silicon migration Chem. Eur. J. 2014, 20, 3554 – 3576

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product 38 a was obtained in 89 % yield instead of the direct arylation product (Scheme 15).[27b] It was noted that the use of dppe as a ligand with Pd(OAc)2 is crucial for achieving the 1,2silicon migration product selectively. Under this optimized conditions, various indole-fused products 38 with versatile functional groups were prepared in good-to-high yields and high selectivities. The mechanism was proposed that the key cationic intermediate C would be formed either through the intermediate B generated by intramolecular electrophilic substitution at 3-position of indole moiety in the arylpalladium A, followed by 1,2-Pd-migration, or through the direct palladation at 2-position in the intermediate A. The intermediate C can be stabilized by silicon b-cation effect. Subsequently, a 1,2-silicon migration in the intermediate C followed by deprotonation and reductive elimination produces the corresponding product.

Scheme 15. Pd-catalyzed C H arylation by 1,2-silicon migration.

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Minireview Intramolecular C H/X H (X = O, N, Si, P, etc.) coupling reactions The intramolecular arylation through C H/X H (X = heteroatom) coupling reaction has been considered as one of the powerful methods for construction of ladder-type heteroacene molecules, which are promising candidates for OFETs due to their high carrier mobility and high stability. Liu and co-workers have developed an efficient intramolecular C H/O H coupling for synthesis of dibenzofurans (40) (Scheme 16).[28a] A

Scheme 17. Cu-catalyzed C H/N H coupling reaction.

Scheme 16. Pd-catalyzed C H/O H coupling.

Pd(OAc)2/IPr catalyst system (IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene) has been developed by using a K2CO3 base and bulky sodium 2,4,6-trimethylbenzoate (MesCO2Na) as an additive under an O2 atmosphere. A four-coordinate PdII complex bearing an anonic pivalate ligand was isolated as a crystal, suggesting that an anionic ligand would promote the C H activation by acting as a proton shuttle. This methodology was applied to the synthesis of a ladder-type heteroacene. Under the optimized conditions, the dibenzofuran moiety in 42 was formed selectively in 65 % yield, which was subsequently subjected with the Gaunt’s[28b] carbazole formation conditions to give the 7H-benzofuro[2,3-b]carbazole derivative 43 in 78 % yield. Chang and co-workers have reported a new synthetic route to carbazoles by a Cu-catalyzed intramolecular C H/N H coupling using hypervalent iodine(III) as an oxidant (Scheme 17).[29] The use of Cu(OTf)2 as catalyst combined with PhI(OAc)2 as oxidant improved the efficiency in the reaction of N-sulfonylamidobiphenyl (44), giving p-benzenesulfonyl carbazole (45) in excellent yield within 10 min at 50 8C. A radical involvement mechanism was proposed. The biphenylamido substrate binds to a CuII center to form a tetradentate copper species, which releases acetic acid and Cu(OTf)2 to form an N-iodoamido species. Subsequent electrophilic aromatic attack of the orthophenyl group onto an amido moiety through a radical pathChem. Eur. J. 2014, 20, 3554 – 3576

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way, followed by deprotonation by an acetoxyl radical, furnishes the corresponding carbazole product. An alternate radical pathway was also considered that involves formation of an aromatic cation radical by a single-electron transfer from the electron-rich arenes to the hypervalent iodine(III). This mild catalytic protocol was applied to the one-step synthesis of N-protected indolo[3,2-b]carbazole. Under the Cu-catalyzed C H/N H coupling conditions, 2,2’’-bis(sulfoamide)-p-terphenyl (46) afforded the ladder-type heteroacene 47, 5,11-dibenzenesulfonyl-5,11-dihydroindolo[3,2-b]carbazole in 40 % yield at 50 8C within 30 min. Kuninobu and Takai et al. have reported a highly efficient synthetic route to silafluorenes (49) by menas of an Rh-catalyzed intramolecular C H/Si H coupling (Scheme 18).[30] A small amount of [RhCl(PPh3)3] (0.5 mol %) in 1,4-dioxane exhibited high catalytic activity for the annulation of biphenylhydrosilane (48). A mechanism was proposed in which, initially, an aryl-Si-Rh-H intermediate forms through Si H bond activation by a Rh complex, in which the Rh center is oriented close to the adjacent C(sp2) H bond, inducing sequential C H activation to form a six-membered rhodacycle. Finally, reductive elimination affords the corresponding silafluorene product. By

Scheme 18. Rh-catalyzed C H/Si H coupling.

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Minireview using this synthetic protocol, a ladder-type bis(silicon)-bridged p-terphenyl has been synthesized. The double annulation of bishydrosilane (50) proceeded efficiently under the Rh-catalyzed conditions by using 3,3-dimethyl-1-butene as additive, producing the corresponding ladder-type silafluorene 51 in 87 % yield. The same research group also developed a new Pdcatalyzed intramolecular C H/P H coupling reaction for construction of dibenzophosphole oxides (Scheme 19).[31] They

Scheme 20. Pd-catalyzed synthesis of 1,2-diphenylacenaphthylene.

moanthracene with teminal alkynes (Scheme 21).[34] The reaction of 9-bromoanthracene (58) with 2-methylbut-3-yn-2-ol carried out in the presence of [PdCl2(PPh3)2], PPh3, CuSO4/Al2O3, and Et3N in benzene at reflux, giving the corresponding 2(aceanthrylen-2-yl)propan-2-ol (59) in high yield together with

Scheme 19. Pd-catalyzed C H/P H coupling reaction.

found that by using Pd(OAc)2 as catalyst, hydrophosphine oxide 52 bearing a biphenyl group afforded the corresponding dibenzophosphole oxide 53 in excellent yield. The reaction proposed to proceed through formation of a six-membered palladacycle from a P H bond cleavage followed by a C(sp2) H activation. This method has been successfully applied to the synthesis of a new ladder-type dibenzophophole oxide. Under the optimized Pd-catalyzed conditions, the bishydrophosphine oxide 54 afforded the ladder-type 5,11-diphenyl-5,11-dihydrobenzo[1,2-b:4,5-b’]bis(phosphindole)-5,11-dioxide (55) in 87 % yield with a mixture of two diastereomers, which are derived from the orientation of the two P=O double bonds. C H/alkyne coupling reactions Similar to the aforementioned internal CP-PAHs, peripheral CPPAHs as subunits of fullerenes also exhibit high electron affinity and relatively low LUMO energy levels with respect to those of acene-type PAHs, making them attractive to use as potential ntype and ambipolar semiconductors.[32] Nowadays, the Pd-catalyzed intermolecular pentannulation of arenyl halides with alkynes is one of the most efficient protocols for synthesis of the peripheral CP-PAHs. This reaction has been developed by Grigg et al. in 1993 using a Pd(OAc)2/PPh3 catalyst system combined with TiOAc in the reaction of 1-iodonaphthalene (56) and 1,2-diphenylacetylene, giving 1,2-diphenylacenaphthylene (57) in 45 % yield (Scheme 20).[33] Later, Garcia-Garibay et al. reported a highly selective synthetic method of the 2-substituted aceanthrylenes by means of a Pd-catalyzed coupling of 9-broChem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 21. Pd-catalyzed cyclopentannulation of bromoanthracenes with terminal alkyne.

a small amount of the Sonogashira product. Mechanistically, it was proposed to proceed through the initial intermolecular carbopalladation of arylpalladium to alkyne and subsequent intramolecular insertion of alkenylpalladium into the double bond of anthracene, followed by b-hydride elimination to give the corresponding product. This protocol was further extended to the reaction of 9,10-dibromoanthracene (60) with 2-methylbut-3-yn-2-ol, affording the corresponding disubstituted cyclopent[hi]aceanthrylene 61 in 75 % yield in the absence of CuSO4/Al2O3. Plunkett et al. have prepared new CP-PAHs of 2,7-bis(trimethylsilyl)cyclopenta[hi]aceanthrylene (62) and 2,8-bis(trimethylsilyl)dicyclopenta[de,mn]tetracene (65), following the methodology shown in Scheme 21, in 62 and 72 % yields, respectively (Scheme 22).[35] The resulting two CP-PAHs were further converted to the p-extended diethynyl CP-PAHs 63 and 66, which exhibited large bathochromic shifts and low optical band-gaps. Especially, the observation of solution-phase fluorescence quenching of the electron donor of poly(3-hexylthiophene) (P3HT) by interaction with the diethynyl CP-PAH indicated its strong electron-accepting behavior.

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Minireview source in the presence of [Pd(dba)2] (10 mol %; dba = dibenzylideneacetone) and P(o-tol)3 (15 mol %). The reaction proceeds through the insertion of the alkyne into an arylpalladium species, followed by intramolecular electrophilic attack of the resulting alkenylpalladium to an anthracene core to form a palladacycle intermediate. Subsequent reductive elimination produces the corresponding product. This approach can be applicable for synthesis of various single and double cyclopentannulated CP-PAHs, such as 1,2,6,7-tetrasubstituted cyclopenta[hi]aceanthrylenes (67 c and 67 d), 1,2,6,7tetraphenyldicyclopenta[cd,jk]pyrene (67 e), 3,4,5,6tetraphenyldicyclopenta[cd,fg]pyrene (67 f), 1,2-disubstituted cyclopenta[cd]perylenes (67 g, and 67 h), and 1,2,7,8-tetrasubstituted dicyclopenta[cd,lm]perylenes (67 i and 67 j). 1,2,6,7-Tetraphenylcyclopenta[hi]aceanthrylene (67 c) has been prepared by Miao et al. following this approach and applied in thin film transistors, which exhibited a high ambipolar behavior with a hole mobility of 0.21 cm 2 V 1 s 1 and an electron mobility of 0.02 cm 2 V 1 s 1.[32] Most recently, Wu and co-workers have reported the first synthetic methodology of [8]circulenes by using the Pd-catalyzed C H/alkyne annulation (Scheme 24).[37] Several substituted [8]circulenes 69 were synthesized in comparable yields through the reaction of tetraiodo-substituted tetraphenylenes

Scheme 22. Pd-catalyzed cyclopenannulation for synthesis of p-extended new CP-PAHs.

Scheme 24. Pd-catalyzed domino C H/alkyne annulation for synthesis of [8]circulenes.

Scheme 23. Pd-catalyzed cyclopentannulation for synthesis of new CP-PAHs.

The Pd-catalyzed cyclopentannulation with internal alkynes as shown in Scheme 20 was widely extended by Mllen et al. by using anthracene, pyrene, and perylene bromides as starting materials (Scheme 23).[36] The desired 1,2-diphenyl and 1,2dithienyl substituted aceanthrylenes 67 a and 67 b were obtained in good yields using 9-bromoanthracene (58) and 1,2diphenylacetylene or 1,2-di(thiophen-3-yl)ethyne as an alkyne Chem. Eur. J. 2014, 20, 3554 – 3576

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68 with symmetric 1,2-diarylalkynes in the presence of Pd(OAc)2 catalyst, NaOAc base, and nBu4NCl at 110 8C. A saddle-shaped structure of [8]circulene 69 a has been determined by X-ray crystallography, indicating its highly strained structure and instability. It was noted that the [8]circulenes 69 a and 69 b, with a methyl group at R, showed a relatively higher stability compared with the [8]circulene 69 c, with a methoxy group at R. Tsuchimoto and Shirakawa et al. developed a novel In-catalyzed annulation of various 2-aryl- and 2-heteroarylindoles with propargyl ethers (Scheme 25).[38] This approach provided a powerful protocol for synthesis of various aryl- and heteroaryl-annulated carbazoles by direct use of aromatic C H bonds without using aryl halides or directing functional groups. In the presence of a catalytic amount of In(ONf)3, the reaction of 2phenylindole (70 a) with methyl propargyl ether produced the corresponding 6-methyl-11H-benzo[a]carbazole (71 a) in 65 % yield. It was noted that other Lewis acids, such as Sc(OTf)3, Zr(OTf)4, InCl3, BF3 Et2O, and TiCl4, were totally inactive. The soft nature of In(OTf)3 induces the activation of the carbon–carbon

3563


Minireview

Scheme 25. In-catalyzed annulation of 2-aryl- and 2-heteroarylindoles with propargyl ethers.

triple bond of propargyl ether, which undergoes regioselective addition with indole, followed by intramolecular SN2 reaction and subsequent aromatization to form the desired product. This annulation reaction is also able to synthesize various heteroaryl-annulated carbazoles, such as 5-methyl-10H-thieno[2,3a]carbazole (71 b), 5-methyl-12H-benzo[4,5]thieno[2,3-a]carbazole (71 c), 5-methyl-12H-benzofuro[2,3-a]carbazole (71 d), and 5-methyl-11,12-dihydroindolo[2,3-a]carbazole (71 e) in good yields. Jiao et al. reported a new Pd-catalyzed cycloaromatization of biaryls with alkynes through dual C H bond activation without using aryl halides toward synthesis of various polycyclic heteroaromatic compounds (Scheme 26).[39] After extensive optimization of reaction conditions, the reaction of 1-methyl-2phenyl-1H-indole (72 a) with 1,2-diphenylacetylene using Pd(OAc)2 (10 mol %), K2CO3 (0.3 equiv), and tetra-n-butylammonium bromide (TBAB; 0.5 equiv), PivOH (1 equiv) in DMF at 100 8C under O2 atmosphere afforded the desired 11-methyl5,6-diphenyl-11H-benzo[a]carbazole (73 a) in 84 % yield. It was noted that the electrophilic aromatic palladation of the 3-position of the indole moiety with a PdII complex forms a indolylpalladium intermediate, which would be a key step for this transformation. Subsequently, the resulting indolylpalladium inserts into alkyne to afford a vinyl palladium species, which undergoes an acid-promoted electrophilic aromatic palladation and subsequent deprotonation to form a seven-membered palladacycle. Reductive elimination of the palladacycle produces the cyclic product. By using this synthetic approach, various structurally interesting polycyclic heteroarenes, such as 5,12-dimethyl-6,7-diphenyl-5,12-dihydroindolo[3,2-a]carbazole (73 b), 12-methyl-6,7-diphenyl-12H-benzofuro[3,2-a]carbazole (73 c), 11,12-dimethyl-5,6-diphenyl-11,12-dihydroindolo[2,3-a]carbazole (73 d), and 5’,6’-diphenyl-2,2’:3’,2’’-diepoxy-p-terphenyl (73 e) have been synthesized in good to high yields. Huang et al. reported the first example of an Rh-catalyzed oxidative C H functionalization using O2 as an oxidant in the Chem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 26. Pd-catalyzed cycloaromatization via dual activation of C H bonds.

reaction of heteroarenes with alkynes, producing various pconjugated polycyclic pyridine salts with a high turnover number up to 740 (Scheme 27).[40] The annulation reaction between 2-phenylpyridine (74 a) and 1,2-diphenylacetylene under O2 atmosphere showed that [Rh(H2O)3Cp*(OTf)2] was the best choice of catalyst for producing the desired 6,7diphenylpyrido[2,1-a]isoquinolin-5-ium triflate salt (75 a) in high yield. Based on the isolated five-membered rhodacycle complex F and the h4-coordinated rhodium complex G, the authors proposed that the initial formation of the intermediate F through C H bond activation would be a rate-limiting step. Subsequent insertion of alkyne into the intermediate F gives a seven-membered rhodacycle G, followed by reductive elimination to afford a complex H, which should be oxidized by O2 and HOTf to regenerate the active RhIII catalyst and the desired product. Cheng et al. reported a similar annulation reaction using [{RhCl2Cp*}2] as a catalyst and Cu(BF4)2 as co-catalyst with a BF4 source under O2 atmosphere.[41] Comparing with the Huang’s results, this catalyst system allowed the reaction to proceed under mild conditions without using an acid. Importantly, both methods enable to construct various p-extended conjugated polycyclic pyridium salts 75 a and 76 a.

Cascade Annulation with Alkynes From the viewpoint of synthetic chemistry and materials chemistry, a cascade reaction using the easily available starting substrates is one of the most useful and convenient methodologies for the formation of the p-extended conjugated polycycles in one process. Kawase and Kubo et al. have reproted a Ni-mediated homo-annulation of various 2-bromo-1-ethynylbenzenes 77 in the presence of zinc dust, producing symmetri-

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Scheme 29. Pd-catalyzed C Br/C Br and C Br/C Sn annulations to dibenzopentalens.

Various symmetric pentalene derivatives were synthesized in high yields, and particularly, the iodoenyne as a substrate produced the fully substituted pentalene 81 d in 60 % yield. Interestingly, the authors proposed that an active catalyst in this reaction should be the Pd nanoparticles. They also reported two examples of the Pd-catalyzed crossover annulation reactions of 2-bromo-1-ethynylbenzene (80 a) and tributyl[2-(phenylethynyl)phenyl]stannanes, affording the dibenzopentalene derivatives 81 a and 81 e in moderate yields. 7,14-Disubstituted zethrenes have been synthesized by the research group of Wu using a modified Pd-catalyzed C I/C I annulation (Scheme 30).[44] A new catalyst system has been developed for an efficient construction of a zethrene core due to the low efficiency of the dibenzopentalene methods. As a result, the reaction of 5-iodo-8-(phenylethynyl)naphthalene

Scheme 27. Rh-catalyzed C H functionalization for synthesis of polycyclic pyridinium salts.

Scheme 28. Ni-mediated C Br/C Br annulation to dibenzopentalene derivatives.

cally substituted dibenzopentalenes 78 in moderate yields (Scheme 28).[42a] A p-extended pentalene derivative 79, 6,13-diphenylpentaleno[1,2-b:4,5-b’]dinaphthalene, has been prepared by Kawase and Takimiya et al. following the Ni-mediated annulation reaction conditions, which has been demonstarted to be good semiconductors for thin film transistors and organic photovoltaics.[42b] Tilley group reported an efficient and versatile Pd-catalyzed C Br/C Br homo-annulation of haloenynes to a variety of pentalene derivatives (Scheme 29).[43] Screening of the reaction conditions exhibited that a high yield of dibenzo[a,e]pentalene (81 a) was obtained in the presence of a [Pd2(dba)3]/P(tBu)3 catalyst system and Cs2CO3, CsF, and a hydroquinone additive using 2-bromo-1-ethynylbenzene (80 a) as a starting substrate. Chem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 30. Pd-catalyzed C I/C I annulation for synthesis of 7,14-disubstituted zethrenes.

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Minireview (82 a) in the presence of Pd(OAc)2 catalyst, P(2-furyl)3 ligand, and Ag2CO3 base in o-xylene afforded the corresponding 7,14diphenyl zethrene 83 a in 73 % yield. It is interesting to note that in comparison with the planar structure of zethrene, the X-ray structures of the 7,14-disubstituted zethrenes 83 a– c showed twisted core structures and remarkable bond alternation of the central two six-membered rings, resulting in the weak aromaticity of these new compounds. Itami and Segawa et al. have demonstrated that a novel C H/C H annulation reaction of arylacetylene (84) to dibenzopentalene (81 a) can be carried out by using PdCl2 as a catalyst, AgOTf as an additive, and o-chloranil as an oxidant (Scheme 31).[45] The substrates scope and limitations, and deu-

Scheme 31. Pd-catalyzed C H/C H annulation to dibenzopentalenes.

terium-labeling experiment indicated that the initial C H activation occurred by an ortho-alkyne-directed electrophilic palladation. Next, the intermolecular insertion of another aryl alkyne to the aryl palladium species produces a vinyl palladium intermediate, which undergoes intramolecular carbopalladation, followed by C H palladation to give a six-membered palladacycle. Subsequent reductive elimination furnishes the product and oxidation of the reduced palladium regenerates the active palladium catalyst. Jin and Yamamoto et al. have developed a novel and selective Pd-catalyzed C Cl/C H crossover annulation of ortho-alkynylarylchlorides (85) and diarylacetylenes (86) for synthesis of the multisubstituted dibenzopentalenes (Scheme 32).[46] The reaction was carried out efficiently in the presence of a Pd(OAc)2 catalyst and a PtBu3 ligand. It is worth noting that the use of the combined DBU and CsOPiv bases is crucial for achieving high yields of products; the yields decreased dramatically when DBU or CsOPiv alone. A variety of functional groups were tolerated, producing the corresponding dibenzopentalene and heteroatom-containing pentalene derivatives in good to high yields. The use of a strong phosphine ligand facilitates the oxidative addition of a Pd0 catalyst to arylchloride to form an ortho-alkynylarylpalladium intermediate, which undergoes double carbopalladations to give a vinyl palladium species. The pivalate-promoted C(sp2) H activation forms a six-membered palladacycle and subsequent reductive elimination furnishes the corresponding product. The use of DBU as a strong Chem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 32. Pd-catalyzed C H/C Br crossover annulation to dibenzopentalenes.

and non-nucleophilic base facilitates the remove of pivalic acid to form the palladacycle intermediate. The Wu group reported an efficient Pd-catalyzed C Br/N H annulation of ortho-alkynylhalobenzenes (80 a) with amines toward synthesis of 5H-cyclopenta[c]quinolone derivatives (87) (Scheme 33).[47a] The reaction carried out in the presence of a Pd(OAc)2/PCy3 catalyst system using tBuONa as a base under reflux conditions gave the products in high yields. Mechanistically, the reaction initially undergoes an intermolecular amination between ortho-alkynylarylpalladium and amine to form ortho-alkynylbenzeneamine, which reacts with the ortho-alkynylarylpalladium species by menas of double carbopalladations, leading to an indenyl vinylpalladium intermediate. Finally, intramolecular amination and reductive elimination take place subsequently to afford the desired product. Similarly, the Pd-catalyzed annulation between ortho-alkynylhalobenzenes (80 a) and 2-alkynylphenols (88) takes place under the similar

3566


Minireview active pharmaceuticals as well as p-functional materials. Takemoto et al. reported a novel Pd-catalyzed cascade annulation of ortho-alkynylphenyl isocyanides (92) and bromo-2,6-dimethylbenzene (93) for construction of the polycyclic carbazole skeleton (94) (Scheme 35).[49] It was noted that the yields were

Scheme 33. Pd-catalyzed C Br/N H and C Br/O H annulations to 5H-cyclopenta[c]quinolone and indeno[1,2-c]chromene derivatives.

pathway, producing the corresponding indeno[1,2-c]chromene derivatives (89) in good to high yields (Scheme 33).[47b] Wang and Lu et al. prepared various 7,9-diaryl-8Hacenaphtho[1,2-c]pyrroles (91) through a new Pd-catalyzed bicyclization of 1,8-diarenynyl naphthalenes (90) and primary amines under air in dimethylsulfoxide (DMSO; Scheme 34).[48] It

Scheme 35. Pd-catalyzed cascade annulation of o-alkynylisocyanides with 2methylarylhalides to p-conjugated polyheterocycles.

improved by slowing adding of isocyanide and the use of a catalytic amount of bulky Ad2PnBu (Ad = adamantane) ligand and pivalic acid as additive. This cascade process was proposed to involve oxidative addition to bromobenzene, insertion of isocyanide and alkyne, C(sp3) H bond activation to form a sevenmembered palladacycle, and reductive elimination. This methodology was further demonstrated to be useful for synthesis of indolo[2,3-a]carbazole derivatives. Under the optimized conditions, the reaction of ortho-alkynylphenyl isocyanide (92) with 1-Boc-2-bromoskatole (95) gave the corresponding polyheterocycle (96) in 36 % yield. Larock et al. reported a facile and direct synthetic methodology for construction of indoloand pyrrolo[2,1-a]isoquinolines in good yields with excellent regioselectivity by using a Cu-catalyzed one-pot annulation of the ortho-haloarylalkynes with indoles or pyrroles (Scheme 36).[50] For example, with the combination of CuI with

Scheme 34. Pd-catalyzed bicyclization of 1,8-diarenynyl naphthalenes and primary amines to 7,9-diaryl-8H-acenaphtho[1,2-c]pyrroles.

was noted that the reactivity largely depended on the solvent; among the solvents tested, only DMSO produced the expected product. The PdCl2 catalyst activates one of two triple bonds of 1,8-diarenynyl naphthalenes to undergo syn-aminopalladation with amine. Subsequently, the adjacent triple bond inserts into the resulting aminopalladium intermediate to form a second vinylpalladiun species, which undergoes intramolecular C N coupling to construct the product and the resulted Pd0 species would be oxidized by DMSO under air to regenerate the active PdII species. Nitrogen-containing p-extended polyheterocycles are utilized widely as precursors of natural products and biologically Chem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 36. Cu-catalyzed one-pot annulation by a hydroamination/ring closure sequence to give tetracyclic polyheterocycles.

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Minireview benzotriazole-1-ylmethanol in DMSO using KOtBu as a base, the reaction of indole (97) with 1-bromo-2-(phenylethynyl)benzene (80 a) gave the corresponding tetracyclic product (98) in 62 % yield. On the basis of the controlled experiments and the corresponding structure of products, the mechanism involves initial hydroamination of 2-bromoalkyne or the alkynylaryl copper complex with indole, giving an enamine-Cu-complex. Subsequent intramolecular C C bond formation through nucleophilic attack and reductive elimination produced the corresponding product.

[2+2+2] Cycloaddition Transition-metal-catalyzed [2+2+2] cycloaddition of alkynes became one of the most engaging synthetic strategies for constructing helicenes and helicene-like molecules, which possess nonplanar ortho-fused p-conjugated polycycles. This strategy is able to convert readily available substrates into complicated aromatic compounds in a simple chemical process and has been considered as a standard methodology for the synthesis of helical compounds. Star and Stary´ et al. demonstrated that the catalytic amounts of [Ni(cod)2] enables cis,cis-dienetriynes (99) to take place the [2+2+2] cycloisomerization to form helicenes with various sizes in good to high yields (Scheme 37).[51]

Scheme 38. Ni-catalyzed [2+2+2] cycloisomerization of aromatic triynes to [5]helicene, [6]helicene, and [7]helicene.

Scheme 39. Ni-catalyzed asymmetric [2+2+2] cycloaddition.

Scheme 37. Ni-catalyzed [2+2+2] cycloisomerization of cis,cis-dientriynes to [5]helicene, [6]helicene, and [7]helicene.

It was noted that [Ni(cod)2] showed a higher catalytic activity than [CpCo(CO)2], giving the corresponding pentahelicene (100) in 64 % yield. This method was also extended to the synthesis of hexahelicene and heptahelicene, while the use of stoichimetric amounts of [Ni(cod)2] gave higher yields than that of catalytic amounts. Most recently, the same group has succeeded in synthesis of dibenzohelicenes using this methodology— dibenzo[5[helicene (102 a), dibenzo[6]helicene (102 b), and dibenzo[7]helicene (102 c) were synthesized in excellent yields using the correponding aromatic triynes (101) (Scheme 38).[52] The pioneering work on enantioselective synthesis of helicenes and helicene-like compounds has been reported by Star and Stary´ et al. through an intramolecular [2+2+2] cycloaddition of triynes (103) in the presence of [Ni(cod)2] catalyst and chiral ligand (S)-( )-BOP. The corresponding tetrahydroChem. Eur. J. 2014, 20, 3554 – 3576

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hexahelicene (104) was achieved in moderate enantioselectivity (up to 42 % ee) (Scheme 39).[53] The improved enantioselectivities have been reported by Tanaka et al. using [Rh(cod)2]BF4 as a catalyst with various chiral ligands for synthesis of helicene-like compounds (Scheme 40). For example, as shown in Scheme 40a, the intramolecular [2+2+2] cycloaddition of naphthol-linked triyne (105) gave the corresponding [7]helicene-like product (106) in 71 % yield with 85 % ee using (R,R)Me-Duphos as a chiral ligand.[54a] Enantioenriched [9]helicenelike compounds with either a fluorenone core (109) or a phosphafluorene core (112) were obtained in 60 and 73 % ee, respectively, in the intermolecular cycloaddition of naphthollinked tetraynes with dialkynyl ketone (108) or dialkynylphosphine oxide (111), respectively, using (S)-Segphos or (R)-tolBINAP, respectively, as a chiral ligand (Scheme 40b and 40c).[54b,c] The highest enantioselectivity (up to 93 % ee) has been obtained by same group in the synthesis of helically chiral 1,1’-bitriphenylenes (115) with a fluorenone core in the reaction of biaryl-linked tetraynes (113) with dialkynyl ketones (114) using a (S)-xyl-Segphos ligand (Scheme 40d).[8] Most recently, Star and Stary´ et al. reported a high ee of 85 % in the Ni-catalyzed asymmetric synthesis of dibenzo[6]helicene (117) using (R)-QUINAP as a chiral ligand and the ee was further increased to 99 % after crystallization of the enantioenriched product in THF/2-propanol solvents (Scheme 41).[52] The formal [2+2+2] cycloaddition of peri-diynes and C C multiple bonds has been considered as a general methodology

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Minireview the desired product and the undesired heptacycle product.[55] The present reaction proceeds through the initial formation of rhodacyclopentadiene followed by inserts to one double bond of norbonadiene to give a seven-membered rhodacycle. Reductive elimination of the Rh catalyst and subsequent thermal elimination of cyclopentene (Cp) gave the corresponding fluoranthene product. The heptacycle byproduct should be formed through the unusal [(2 + 2) + (2 + 2)] cycloaddition of diyne with two double bond of NBD. Similarly, treatment of 1,8-bis(phenylethynyl)naphthalene (90) with 1,2-diphenylacetylene in place of NBD generated 7,8,9,10-tetraphenylfluoranthene (119) in high yield using [RhCl(PPh3)2] as a catalyst (Scheme 42 b).[56] This method has been successfully applied to the preparation of indenocorannulene (121) using 2,3-diethynylcorannulene (120) as a starting material (Scheme 42 c).[56]

Scheme 40. Rh-catalyzed enantioselective synthesis of helicene-like compounds.

Scheme 42. Rh-catalyzed synthesis of fluoranthene derivatives.

Scheme 41. Ni-catalyzed asymmetric synthesis of dibenzo[6]helicene.

for construction of fluoranthene framework. Sigel et al. prepared 7,10-disubstituted fluoranthene derivatives through a [2+2+2] cycloaddition of 1,8-dialkynylnaphthalenes (90) with norbornadiene (NBD) in the presence of a rhodium catalyst. As shown in Scheme 42a, 7,10-diphenylfluoranthene (118) formed as a sole product in 96 % yield by using [{RhCl(cod)2}2] or [Rh(OAc)2]·H2O as a catalyst, while it was found that in the presence of [RhCl(PPh3)3], the reaction afforded a 77:23 mixture of Chem. Eur. J. 2014, 20, 3554 – 3576

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Kuo and Wu et al. reported a Pd-catalyzed formal [2+2+2] cycloaddition of diynes with aryliodides for synthesis of the highly substituted benzo[k]fluoranthene-based linear acenes.[57] For example, the reaction of 1,8-bis(phenylethynyl)naphthalene (90) with 1,2-diiodobenzene in the presence of a Pd(OAc)2 catalyst and two equivalents of Ag(OAc) gave the corresponding 7,12-diphenylbenzo[k]fluoranthene (122) in 85 % yield (Scheme 43). The proposed mechanism involves syn-addition of the arylpalladium to one triple bond of diyne, which generates an alkenyl palladium species. Subsequent intramolecular carbopalladation converts the resulting alkenylpalladium to the arylbutadienylpalladium intermediate. The intramolecular cyclization furnishes a high oxidation-state palladabenzocycloheptatriene species, which undergoes reductive elimination to afford the corresponding product and PdI2. It was noted that

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Minireview

Scheme 45. Pd-catalyzed trimerization of benzyne.

Olefin Ring-Closing Metathesis

Scheme 43. Pd-catalyzed cycloaddition of diyne with diiodie and tetraiodide.

PdI2 would react with Ag(OAc) to regenerate Pd(OAc)2. Under similar conditions, the twofold [2+2+2] cycloaddition carried out between 1,8-bis(phenylethynyl)naphthalene (90) and 1,2,4,5-tetraiodobenzene in a one-pot process, giving the symmetric benzo[1,2-k:4,5-k’]difluoranthene product (123) in a moderate yield. Murakami et al. demonstrated that an iridium–phosphine catalyst system can promote the [2+2+2] cycloaddition of silicon-bridged 1,6-diynes with alkynes to form silafluorene derivatives.[58] This method has been extended to the synthesis of a ladder-type molecule. A double [2+2+2] cycloaddition between the silicon-bridged tetrayne (124) with 1,4-dimethoxybut-2-yne in the presence of a [{IrCl(cod)2}2] catalyst and a PPh3 ligand under heating afforded the corresponding p-conjugated ladder-type silafluorene (125) in 58 % yield, which exhibited high fluorescence efficiency (91 %) in hexane (Scheme 44).

Olefin ring-closing metathesis (RCM) has been widely used in synthetic chemistry as a powerful and useful methodology; it has been also applied to PAHs and PHAHs. King et al. desired two tetravinyl terphenyls and used them as a RCM precursor for the preparation of large PAHs.[60] As shown in Scheme 46,

Scheme 46. The double RCM for synthesis of PAHs.

the double RCM of 2,2’’,4’,6’-tetravinyl-1,1’:3’,1’’-terphenyl (128) and 2,2’,2’’,5’-tetravinyl-1,1’:4’,1’’terphenyl (130), in the presence of Grubbs catalysts (Ru-1 and Ru-3) or Schrock catalyst (Mo-1), Scheme 44. Ir-catalyzed cycloaddition for synthesis of ladder-type silafluorene derivative. was carried out efficiently to give the corresponding benzo[m]tetraphene (129) and benzo[k]tetraphene (131), respecThe use of benzyne as an alkyne source for the metal-catatively, while it was noted that the use of Ru-3 and Molyzed trimerization is a very efficient method for constructing 1 showed a higher activity than using Ru-1. Koning et al. synvarious PAHs.[59] As exemplified by Prez and Guitin et al., the thesized PHAHs containing a carbazole moiety using the RCM trimerization of 4,5-difluoro-2-(trimethylsilyl)phenyl triflate as a key reaction.[61] As shown in Scheme 47, treatment of the (126) took place with a [Pd(PPh3)4] catalyst and CsF, producing the corresponding symmetrical 2,3,6,7,10,11-hexafluorotripheBoc-protected 3,3’-divinyl-1H,1’H-2,2’-biindole (133) and 2-(2nylene (127) in good yield (Scheme 45).[59a] The reaction is (prop-1-en-2-yl)thiophen-3-yl)-3-vinyl-1H-indole (136), which were prepared from dicarbonyl compounds using Wittig alkethought to proceed by formation of a five-membered palladanylation, with the Grubbs second-generation catalyst (Ru-1) afcycle intermediate.

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Minireview successfully extended by Scott and co-workers to synthesis of 1,8,9-perinaphthothioxanthene (142) by the reaction of 9-(penta-1,4-diyn-3-ylidene)-9H-thioxanthene (141) in the presence of a [Ru(cymene)Cl2PPh3] catalyst (Scheme 50 a).[7a] Importantly, although the yield was low, they have succeeded in a short synthesis of coronene (144) from the Rucatalyzed double naphthoannulation of 9,10-di(penta-1,4-diyn-3-ylidene)-9,10-dihydroanthracene (143) (Scheme 50 b). Surprisingly, a significantly high yield

Scheme 47. The RCM for synthesis of PHAHs.

forded the desired indolo[2,3-a]carbazole (134) and thieno[3,2a]carbazole (137), respectively. RCM has been applied to the direct synthesis of [5]-, [6]-, and [7]helicenes as exemplified by Collins et al.[62] Two sets of reaction conditions, Ru-1 catalyst under microwave irradiation and Ru-2 catalyst at 40 8C, have been established to be efficient catalyst systems for the facile formation of various helicenes from the corresponding divinyl precursors (138) (Scheme 48). They also reported an enantioselective synthesis Scheme 49. Asymmetric RCM for synthesis of chiral [7]helicene.

Scheme 48. The RCM for synthesis of helicenes.

of [7]helicene (140) by means of asymmetric RCM with a new Ru-4 catalyst bearing C1-symmetric N-heterocyclic carbene as a ligand.[63] In addition, the use of C6F6 as a solvent and vinylcyclohexane as an additive is crucial for achieving a high enantioselectivity of [7]helicene in 80 % ee (Scheme 49).

Electrophilic Aromatization The carbon–carbon triple bonds activated by certain metal complexes can generate cationic species or p-coordinated electron-deficient C C triple bonds, which are capable of undergoing intramolecular electrophilic cyclization onto an aromatic ring to form various poly aromatic compounds. Merlic et al. developed a Ru-catalyzed aromatization of 1-aryl-1buten-3-ynes to construct the naphthalene molecules.[64] They demonstrated that this naphthoannulation involves the initial formation of a ruthenium–vinylidene species followed by an electrophilic aromatic substitution. This methodology has been Chem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 50. Ru-catalyzed electrophilic naphthoannulation.

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Minireview of 86 % of coronene has been achieved by Liu and co-workers using [Ru(CH3CN)2(PPh3)Tp][PF6] (Tp = tris(1-pyrazolyl)borate) as catalyst for the same reaction.[7b] By using this conditions, coronene derivatives with various substituents and oligoacene derivatives could be synthesiszed efficiently. A Ru-catalyzed regioselective aromatization has been reported by Liu et al. for synthesis of ethene-bridged para-phenylene oligomers (146) (Scheme 50 c).[65] By using [Ru(CH3CN)2(PPh3)Tp][SbF6] as a catalyst, the double annulation of the terminal arylalkyne substrate (145) occurred between the less-hindered C H bond of the central aromatic ring and the adjacent terminal alkyne, presumably due to the bulky [Ru(PPh3)Tp] fragment. Metal salts with a high electron affinity for p-systems, such as PtII, AuI and AuIII, are also powerful catalysts for triggering the electrophilic aromatization. Frstner and co-workers have developed an efficient approach to phenantrene derivatives 100 and 149 based on a Pt-catalyzed cyclization of the alkynylated biaryl substrates 147 and 148 (Scheme 51 a).[66] Among

Scheme 52. Au-catalyzed double annulation of arenyl diynes.

benzocarbazoles and the heteroaryl-annulated carbazoles have been synthesized efficiently.

Cross-Coupling Reactions Double cross-coupling reactions

Scheme 51. Pt-catalyzed electrophilic cycloaromatization.

various metal salts tested, such as PtCl2, GaCl3, AuCl3, InCl3, and Ru complexes, the PtCl2 catalyst showed a unique 6-endo-dig cyclization selectivity and high efficiency. Liu and co-workers have reported a regioselective annulation approach to the ethene-bridged para-phenylene oligomers (151) using a PtCl2/ CO catalyst system (Scheme 51 b).[65] It was interesting to note that the regioselectivity of the Pt-catalyzed electrophilic aromatization is completely different from the Ru-catalyzed annulation as shown in Scheme 50 c, which proceeds through the annulation of the hindered C H bond of an aromatic ring with the adjacent internal alkyne moiety. Jin et al. and Ohno et al. have reported independently a gold-catalyzed double annulation of arenyl diynes (152) (Scheme 52).[67, 68] By using NaAuCl4 in ethanol or [AuClPPh3]/Ag(OTf) in acetonitrile, the desired

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Transition-metal-catalyzed cross-coupling between organometallic reagents and organic halides is a classical synthetic methodology for the formation of C(sp2) C(sp2) bonds. Shimizu and co-workers have developed a facile and efficient synthetic approach to various PAHs by means of a Pd-catalyzed double cross-coupling reaction of vic-diborylated alkenes and arenes with 2,2’-dibromobiaryls.[69] As examplified in Scheme 53 a, the double cross-coupling of 2,2’-dibromo-1,1’-binaphthalene (154) and 3,3’-dibromo-2,2’-bibenzo[b]thiophene (155) with 1,2-bis(pinacolatoboryl)alkenes 156 a and 156 b, respectively, in the presence of [Pd(PPh3)4] catalyst, K2CO3 base, and water additive afforded the desired [5]helicene (157) and dibenzothienobenzene (158), respectively, in good yields. The annulation of vicbis(pinacolatoboryl)phenanthrene (156 c) with 2,2’-dibromo1,1’-biphenyl (159) and 2,2’-dibromo-3,3’-bithiophene (160) also underwent the Pd-catalyzed double cross-coupling using K3PO4 (3 m aq) as base to give the corresponding products, dibenzo[g,p]chrysene (161) and triphenyleno[1,2-b:4,3-b’]dithiophene (162), respectively, in excellent yields (Scheme 53 b). This methodology was also applied to the regiospecific synthesis of dibenzo[a,h]anthracene (165) and dibenzo[a,j]anthracene (166) through a double coupling reaction of 1,2-bis(pinacolatoboryl)arene (156 d) with 1,4-dibromo-2,5-bis((Z)-2-bromovinyl)benzene (163) and 1,5-dibromo-2,4-bis((Z)-2-bromovinyl)benzene (164), respectively (Scheme 53 c).[69c] A new aromatic annulation through a Pd-catalyzed double cross-coupling reaction of 9-stannafluorenes and 1,2-dihaloarenes has been reported by Shimizu and co-workers.[70] By using [Pd(PtBu3)2] (5 mol %) in THF at 60 8C, an efficient double cross-coupling reaction of 9,9-dimethyl-9-stannafluorene (167) with 1,2-dibrobenzene produced the expected triphenylene product (168) in 90 % yield (Scheme 54 a). This reaction condition can be compatible with various dibromoheteroarenes, giving a variety of triply-annulated PHAHs in good to excellent yields. Under the same conditions, a double annulation of 9,9dimethyl-9-stannafluorene (167) with tetrabromoarenes afford-

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Scheme 54. Double cross-coupling reactions of 9-stannafluorenes with dibromo- and tetrabromoarenes.

Scheme 53. Double cross-coupling reaction of 1,2-diborylalkenes and -arenes with dibromoarenes.

ed the twisted polycycle products, phenanthro[9,10-b]triphenylene (169) and diphenanthro[9,10-b:9’,10’-d]thiophene (170) in good to high yields, respectively (Scheme 54 b). A new series of tetracene tetracarboxylic diimides has been synthesized by Wang et al. based on the Pd-catalyzed double annulation.[71] For example, the cross-coupling of 9,9-dimethyl-9-stannafluorene (167) with 2,3,6,7-tetrabromo-1,4,5,8-naphthalene tetracarboxylic diimide as a coupling partner in the presence of [Pd(PtBu3)2] and CsF in THF at 70 8C proceeded smoothly to give the desired tetrabenzotetracene diimide (171) in 42 % yield. The introduction of imide moieties into tetracene makes the p-extended product promising to use as a potential airstable n-type semiconductor. X-Arylation (X = N, O, P, and Si) through cross-coupling reactions The cross-coupling of di(pseudo)halobiphenyls with primary amines through a double N-arylation and an intramolecular OChem. Eur. J. 2014, 20, 3554 – 3576

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arylation of 2’-hydroxylbiphenyl-2-yl halides or sulfonates have been developed as useful synthetic approaches to carbazole and dibenzofuran derivatives. Nozaki and co-workers synthesized hetero[7]helicenes using N- and O-arylations as the key reactions.[72] Under the optimized conditions of [Pd2(dba)3], xantphos, and K3PO4 in xylene at 100 8C, the double N-arylation of racemic 4,4’-biphenanthryl-3,3’-ylene dinonaflate (172 a) with aniline afforded the desired aza[7]helicene (173 a) in 88 % yield and the (P)-aza[7]helicene enantiomer (173 b) was obtained in 99 % ee from the enantiomerically pure (S)-4,4’-biphenanthryl-3,3’-ylene dinonaflate (172 b, 99 % ee) without changing the absolute configuration (Scheme 55 a).[72a] Oxa[7]helicene (175 a) can be prepared through O-arylation of 3’-hydroxyl-4,4’-biphenantryl-3-yl nonaflate (174 a) using biphenylphosphine as ligand in place of xantphos as shown in Scheme 55 b.[72a] However, it was mentioned that a slightly decreased enantioselectivity of the corresponding (P)-oxa[7]helicene (175 b, 92 % ee) was obtained from the (S)-configurated substrate (174 b, 99 % ee), suggesting the racemization of oxa[7]helicene under the reaction conditions. The X-ray analysis showed that oxa[7]helicene (175) has a less distored structure than aza[7]helicene (173), which resulted in the weaker steric repulsion of the terminal two rings in oxa[7]helicene. l5-Phospha[7]helicene was achieved by the same group by means of a Pd-catalyzed P-arylation.[72b] Reduction of 3’-[ethoxy(phenyl)phosphoryl](4,4’-biphenanthren)-3-yl triflate (176) with LiAlH4, followed by a Pd-catalyzd intramolecular P-arylation of the resulting 3’-(phenylphosphino)(4,4’-biphenanthren)-3-yl trif-

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Scheme 56. Pd-catalyzed N- and O-arylation to ladder-type heteroacenes.

Scheme 55. Pd-catalyzed N-, O-, and P-arylation to hetero[7]helicenes.

late (177) afforded the desired l3-phospha[7]helicene, which was directly oxidized to l5-phospha[7]helicene (178) in a 34 % overall yield (Scheme 55 c). The ladder-type heteroacenes have been effectively synthesized by Nozaki and co-workers through the Pd-catalyzed N- and O-arylation (Scheme 56 a and 56b).[73] The double N-arylation of aniline with the dinonaflate substrate (179) and the O-arylation of terphenyldiol (181) produced indolo[3,2-b]carbazole (180) and dibenzo[d,d’]benzo[1,2b:4,5-b’]difuran (182) in good yields, respectively. The combination of K3PO4 or KOAc with 2,6-di-tert-butyl-4-methylphenol (BHT) is important for increasing the chemical yields. A similar double N-arylation has been reported by Valiyaveettil et al. to prepare a ladder-type heteroacene (183) containing thiophene and pyrrole rings from 3,3’-dibromo-2,2’-bibenzo[b]thiophene (155) with 4-hexylaniline (Scheme 56 c).[74] Liang et al. reported a novel Pd-catalyzed Si-arylation for synthesis of benzosilolo[2,3-b]indoles (185) (Scheme 57).[75] Mechanistically, the reaction proposed to involve a C(sp3) Si bond cleavage and subsequent C(sp2) Si bond formation. The facts that the addition of 4-nitrobenzaldehyde improved the yield of product and observation of CH4 led them to consider the generation of a Me-Pd-OR intermediate, which would proceed a b-hydrogen elimination to give a MePdH species, followed by reductive elimination to regenerate the active Pd0 catalyst. Moreover, the direct reductive elimination of MePdBr to Pd0 also could not rule out due to the observation of MeBr. Chem. Eur. J. 2014, 20, 3554 – 3576

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Scheme 57. Pd-catalyzed Si arylation through C(sp3) Si bond cleavage.

Summary and Outlook The increasing demand of p-conjugated polycycles in organic electronics and pharmaceutical chemistry has stimulated chemists to develop new synthetic methodologies for construction of them. In this article, we described highly efficient and selective metal-catalyzed strategies for the synthesis of a variety of structurally diverse p-extended poylcycles including five- and six-membered rings fused polyaromatic hydrocarbons and heteroatom-containing p-conjugated polycycles. Various types of new and practical annulations promoted by metal catalysts, especially transition metals, have been introduced, that generated various planar, curved, and twisted complex molecules with high regio-, chemo-, and stereocontrol. New metal catalyst systems combined with suitable ligands, bases, and oxidants, and the elegant and concise design of the starting substrates not only allow the generation of the target molecules precisely with high functional group compatibility, but also offer opportunities to find out accidental discoveries

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Minireview including new activity and selectivity, and novel molecules, which are not easily prepared by catalyst-free methods. Among the reactions described in this article, intramolecular C H functionalization is an attractive method to form the desired molecules in a straightforward procedure without using the pre-functionalized substrates, even though they are still not easy to prepare. On the other hand, the cascade annulation approach also seems to be promising—it accomplishes diverse reaction patterns in a single process using readily available starting substrates; however, it still limited to the synthesis of the rather simple molecules. It should be noted that, although some of the p-conjugated polycycles outlined in this paper have been demonstrated to be useful as functional materials and biologically important substances, most of the compounds were limited to study the structure–property relationships. Hence, the development of new, flexible, and versatile metal-catalyzed annulations based on the consideration of the material functionalities is highly desirable toward the creation of novel p-conjugated polycycles.

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Published online on March 3, 2014

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Siloxy alkynes in annulation reactions.

Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps.

Regioselective syntheses of 1,2-benzothiazines by rhodium-catalyzed annulation reactions.

alkyne annulation reactions via aerobic copper catalysis.

Cyclization and annulation reactions of nitrogen-substituted cyclopropanes and cyclobutanes.

An annulation reaction for the synthesis of cross-conjugated triene-containing hydroindanes from acyclic precursors.

Dynamic kinetic asymmetric [3 + 2] annulation reactions of aminocyclopropanes.

Conjugated BODIPY DYEmers by metathesis reactions.

Enantioselective [4 + 1] Annulation Reactions of α-Substituted Ammonium Ylides To Construct Spirocyclic Oxindoles.

Annulation reactions of allenyl esters: an approach to bicyclic diones and medium-sized rings.

Proline-catalyzed sequential syn-Mannich and [4 + 1]-annulation cascade reactions to form densely functionalized pyrrolidines.

Organocatalyzed oxidative N-annulation for diverse and polyfunctionalized pyridines.

Synthesis of sulfur-bridged polycycles via Pd-catalyzed dehydrogenative cyclization.

Dibromoisobenzofuran as a formal equivalent of didehydroisobenzofuran: reactive platform for expeditious assembly of polycycles.

Boron-mediated sequential alkyne insertion and C-C coupling reactions affording extended π-conjugated molecules.

Double carbometallation of alkynes: an efficient strategy for the construction of polycycles.

Conjugated polymer nanomaterials for theranostics.

intramolecular Diels-Alder reaction of enediynes affording dihydrocoumarin-fused polycycles.

Polymer conjugated retinoids for controlled transdermal delivery.

Acid-catalyzed domino reactions of tetraarylbut-2-yne-1,4-diols. Synthesis of conjugated indenes and inden-2-ones.

The synthesis of functionalized bridged polycycles via C-H bond insertion.

A general catalytic reaction sequence to access alkaloid-inspired indole polycycles.

Titanium-catalyzed hydroalumination of conjugated dienes: access to fulvene-derived allylaluminium reagents and their diastereoselective reactions with carbonyl compounds.

Biliary excretion of conjugated sulfobromophthalein (BSP) in constitutional conjugated hyperbilirubinemias.