Synthesis of Nanographenes, Starphenes, and Sterically Congested

Article Cite This: Acc. Chem. Res. XXXX, XXX, XXX−XXX

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Synthesis of Nanographenes, Starphenes, and Sterically Congested Polyarenes by Aryne Cyclotrimerization Published as part of the Accounts of Chemical Research special issue “Advanced Molecular Nanocarbons”. Iago Pozo, Enrique Guitiań , Dolores Peŕ ez, and Diego Peña* Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS) and Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain Downloaded via NOTTINGHAM TRENT UNIV on August 15, 2019 at 15:22:05 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

CONSPECTUS: In recent years, synthetic transformations based on aryne chemistry have become particularly popular, mostly due to the spread of methods to generate these highly reactive intermediates in a controlled manner under mild reaction conditions. In fact, aryne cycloadditions such as the Diels− Alder reaction are nowadays widely used for the efficient preparation of polycyclic aromatic compounds. In 1998, our group discovered that arynes can undergo transition metalcatalyzed reactions, a finding that opened new perspectives in aryne chemistry. In particular, Pd-catalyzed [2 + 2 + 2] cycloaddition of arynes allowed the straightforward synthesis of triphenylene derivatives such as starphenes or cloverphenes. We found that this reaction is compatible with different substituents and sterically demanding arynes as starting materials. This transformation is especially useful to increase the molecular complexity in one single step, transforming molecules formed by n cycles in structures with 3n + 1 cycles. In fact, we took advantage of this protocol to prepare a large variety of sterically congested polycyclic aromatic hydrocarbons such as helicenes or twisted polyarenes. Soon after the discovery of the reaction, the co-cyclotrimerization of arynes with other reaction partners, such as electron deficient alkynes, significantly expanded the potential of this transformation. Also the use of catalysts based on alternative metals besides Pd (e.g., Ni, Cu, Au) or the use of other strained intermediates such as cycloalkynes or cycloallenes added value to this reaction. In addition, we realized that the Pd-catalyzed aryne cyclotrimerization reaction is particularly useful for the bottom-up preparation of well-defined nanographenes by chemical methods. Although the extreme insolubility of these planar nanographenes hampered their manipulation and characterization by conventional methods, recent advances in single molecule on-surface characterization by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) with functionalized tips under ultrahigh vacuum (UHV) conditions, permitted the impressive visualization of these nanographenes with submolecular resolution, together with the examination of the corresponding molecular orbital densities. Moreover, arynes have been shown to possess a rich on-surface chemistry. In particular, arynes have been generated and studied on-surface, showing that the reactivity is preserved even at cryogenic temperatures. On-surface aryne cyclotrimerization was also demonstrated to obtain large starphene derivatives. Therefore, it is expected that the combination of aryne cycloadditions and on-surface synthesis will provide notable findings in the near future, including the “à la carte” preparation of graphene materials or the synthesis of elusive molecules with unique properties.

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INTRODUCTION

mediates proved to be particularly useful. In particular, aryne cycloadditions allow for a significant increase in the molecular structural complexity by introducing benzologue moieties through the formation of two C−C bonds in one step.4,5 For example, our group has recently taken advantage of the efficiency of aryne cycloadditions to prepare decacene precursors6 or epoxycyclacenes,7 among other relevant polyarenes.

At the beginning of this century, the emergence of graphene shocked the scientific community and deeply influenced several fields such as materials science and condensed matter physics. Soon after the discovery of graphene, organic synthesis in solution was proposed as a privileged bottom-up approach to obtain well-defined graphene molecules.1,2 Synthetic methodologies that had been introduced during the last century to prepare polycyclic aromatic hydrocarbons (PAHs) were rapidly adapted to obtain nanographene derivatives.1−3 Among the most efficient methodologies to obtain PAHs, those based on the chemistry of short-lived aryne inter© XXXX American Chemical Society

Received: May 22, 2019

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DOI: 10.1021/acs.accounts.9b00269 Acc. Chem. Res. XXXX, XXX, XXX−XXX

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Accounts of Chemical Research

starting from molecules with n cycles. Herein we have selected some examples of Pd-catalyzed aryne cyclotrimerizations to illustrate the potential of this methodology for the preparation of trigonal PAHs and nanographenes.11,12

In 1998, we expanded the synthetic utility of arynes by combining the generation or these strained cyclic intermediates with the use of transition metal catalysis. We observed that the generation of benzyne (1) in the presence of a palladium(0) complex led to its cyclotrimerization to obtain triphenylene (2, Scheme 1).8

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SYNTHESIS OF SUBSTITUTED TRIPHENYLENES Soon after the discovery of the Pd-catalyzed aryne cyclotrimerization, it was found that a large variety of transition metal complexes are capable of promoting this transformation. For example, it was reported that Ni(0),9 Cu(I),13 and Au(I)14 complexes can efficiently promote the cyclotrimerization of benzyne. It was also found that the reaction is compatible with acceptor or donor substituents on the aryne such as F (6, Figure 1a) and OMe (9, Figure 1b), respectively.8 In terms of regioselectivity, the cyclotrimerization of asymmetric arynes frequently afforded a mixture of both the asymmetric and the symmetric trimers in a statistical proportion (3:1). However, we observed exceptions such as the cyclotrimerization of 3methoxybenzyne (9), which afforded triphenylenes 10 and 11 in a 93:7 ratio (Figure 1b). Remarkably, the reaction is compatible with severe steric hindrance, as was demonstrated by the cyclotrimerization of aryne 13 to obtain hexamethyltriphenylene 14 (Figure 1c).15 In addition, the reaction is not limited to arynes, since other strained intermediates such as cyclohexyne (16) can be involved in the cyclotrimerization to obtain polycyclic hydrocarbon 17 (Figure 1d).16 Although ortho-(trimethylsilyl)aryl triflates such as 4, 5, 8, or 12 are the most commonly used compounds to generate arynes in situ, benzoic acid (18)17 and boronate 1918 were also reported as benzyne precursors in Pdcatalyzed cyclotrimerization reactions under modified conditions (Figure 1e). In fact, these alternatives allowed for the introduction of diverse substituents, including Cl, CF3, t-Bu, and OCF3 among other groups. The cyclotrimerization reaction is compatible with heterocyclic arynes (Figure 2). For example, in 2017 Garg, Houk, and co-workers described the [2 + 2 + 2] cycloaddition of regioisomeric indolynes 20, 21, and 22, which were generated

Scheme 1. Palladium-Catalyzed [2 + 2 + 2] Cycloaddition of Benzyne8a

a Conditions: (a) 3, nBuLi, THF, 0 °C, 12 h; (b) 4, CsF, ACN, rt, 12 h.

We found that the yield of this cyclotrimerization reaction strongly depends on the method to generate highly reactive benzyne in situ. While the generation of benzyne by reaction of ortho-dibromobenzene (3) with BuLi led to triphenylene (2) in 40% yield, fluoride-induced decomposition of ortho(trimethylsilyl)phenyl triflate (4) afforded triphenylene (2) in 83% yield. We proposed a mechanism based on a [2 + 2 + 2] cycloaddition reaction, through the coordination of benzyne to the metal and formation of the palladacycle A as the key intermediate.9 Two features make this transformation particularly interesting for the preparation of large PAHs and nanographenes: (1) the ready availability of ortho(trimethylsilyl)aryl triflates to be used as precursors of substituted or polycyclic arynes10 and (2) the significant increase in the molecular complexity in one single step, that is, the easy preparation of structures formed by 3n + 1 cycles

Figure 1. Synthesis of triphenylene derivatives by Pd-catalyzed aryne and cyclohexyne [2 + 2 + 2] cycloaddition (in bold the bonds formed in the cycloaddition). B


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Figure 2. Selected examples of the cyclotrimerization of heterocyclic arynes.

Figure 3. Cyclotrimerization of polycyclic arynes to obtain helicenes, twisted and bowl-shaped derivatives.

congested derivatives enhances their solubility allowing full spectroscopic characterization. For example, 1,2-naphthyne (33) afforded a mixture of trimers 34 and 35 in 60% yield and 1:2.7 ratio (Figure 3).21 It should be mentioned that in the case of sterically demanding polycyclic arynes such as 33, Pd2(dba)3 is a superior palladium source compare to Pd(PPh3)4, which presents bulky and strongly coordinated phosphine ligands. More remarkable, the cyclotrimerization of phenanthryne 36 led to the isolation of hexabenzotriphenylene 37 (68% yield), a compound with three pentahelicene moieties in its structure that was isolated as a thermodynamically unstable C2 symmetric conformer. Notably, the racemization of this chiral C2 conformation is a rapid process (ΔG⧧ = 11.7 kcal/mol), while the conversion to the thermodynamically more stable propeller-shaped D3 conformation has a higher

from the corresponding triflates, leading to pyrrole-fused triphenylenes 23−28.19 In another remarkable example, Hamura and co-workers trimerized oxygen-substituted arynes 29 and 30 to isolate star-shaped triphenylene derivatives 31 and 32, respectively.20

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SYNTHESIS OF STERICALLY CONGESTED NONPLANAR TRIPHENYLENE DERIVATIVES The Pd-catalyzed [2 + 2 + 2] cycloaddition is particularly powerful for the cyclotrimerization of polycyclic arynes, including sterically congested ones, to obtain nonplanar helicene-based polyarenes. Large PAHs are normally flat compounds that present a significant aggregation tendency and therefore are insoluble in most organic solvents, an issue that limits the manipulation and characterization of these molecules. However, the distortion from planarity of sterically C


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Accounts of Chemical Research barrier (ΔG⧧ = 26.2 kcal/mol), which makes the C2 conformer relatively persistent at room temperature.22 The cyclotrimerization of phenanthryne 38 afforded the expected mixture of trimers 39 and 40, while the [2 + 2 + 2] cycloaddition of phenanthryne 41 led to the formation of double helicene 42, a molecule formed by a pentahelicene and a heptahelicene with two rings in common.23 In this case, compound 42 was isolated as a single cyclotrimerization product, while the corresponding regioisomeric propeller-like trimer was not detected. Similarly, trimerization of triphenylyne 43 afforded compound 44 formed by the cata-fusion of 13 benzene rings.24 A remarkable example to illustrate the potential of this methodology is the cyclotrimerization of pentahelicene-based aryne 45 to obtain soluble trimer 46 composed of six pentahelicene subunits. The synthesis of this compound was independently reported by Kamikawa’s group25 and by us26 through Pd-catalyzed cyclotrimerization of aryne 45 and by Gingras and co-workers via Ni-promoted Yamamoto coupling of the corresponding dibromopentahelicene.27 Similarly to trimer 37, compound 46 was isolated as a thermodynamically metastable saddle-like conformation, which isomerized by heating in solution to a more stable propeller-like structure with a D3 symmetry. In 2012, we described the Pd-catalyzed cyclotrimerization of aryne 47 to obtain hexabenzotrianthrycene 48 (C102H60), a 3fold symmetric polyarene with a molecular core formed by 16 cata-fused benzene rings. We proposed the trivial name [16]cloverphene (clover-like phene) to refer to this polyaromatic core. The presence of six phenyl groups attached to the cloverphene core induces a distortion from planarity, which crucially enhances the solubility of the molecule to allow full spectroscopic characterization.28 Structures with five-membered rings derived from acenaphthylene and corannulene were also obtained by trimerization of the corresponding arynes. For example, cyclotrimerization of acenaphthylyne (49) led to the isolation of decacyclene (50),16 while [2 + 2 + 2] cycloaddition of corannulyne (51) afforded the nonplanar polyarene 52 formed by three connected corannulene bowls (Figure 3).29

Figure 4. Synthesis of alkyl and alkoxyl substituted polyarenes.

This methodology has also been used in the synthesis of PAHs that incorporate four-membered rings (Figure 4), in particular, Pd-catalyzed cyclotrimerization of dihexyl-substituted biphenylyne 57a to obtain tris(benzocyclobutadieno)triphenylene 58a34 or the cyclotrimerization of dihexyloxysubstituted biphenylyne 57b to afford trimer 58b (Figure 4).35 Substituted cloverphenes were also obtained by this synthetic methodology. Thus, cyclotrimerization of tetrakis(hexyloxy)triphenylyne 59 led to the isolation of substituted [13]cloverphene 60, a molecule with a strong tendency to selfassemble.36 The co-cyclotrimerization of different arynes has extended the synthetic utility of this reaction. For example, in the presence of catalytic amounts of Pd(PPh3)4, the co-generation of aryne 59 and benzyne (ratio 1:4), generated from triflates 61 and 4, respectively, led to the isolation of 62 and 63 in 42% and 9% yields, respectively (Scheme 3). Similarly, reaction between triflates 61 and 64 (ratio 1:4) in the presence of CsF and Pd2(dba)3 led to the cotrimerization of aryne 59 with two molecules of phenanthryne 36, to afford substituted [11]cloverphene 65 in 30% yield.37 By contrast, cocyclotrimerization reactions of arynes with electron-deficient alkynes are more efficient and chemoselective.9 For example, treatment of triflate 61 with CsF in the presence of Pd(PPh3)4 and dimethylacetylenedicarboxylate led to the isolation of compound 66 (65% yield) by cocyclotrimerization of two molecules of aryne 59 and one alkyne (Scheme 4). However, the reaction of triflate 61 and the same alkyne in the presence of Pd2(dba)3 afforded compound 67 (62% yield) by co-cycloaddition of one aryne with two alkynes.36

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SYNTHESIS OF PLANAR EXTENDED TRIPHENYLENE DERIVATIVES As mentioned before, planar large PAHs are insoluble in most organic solvents, which hampers the manipulation and characterization of these molecules. A frequently used approach to increase the solubility of these compounds is the introduction of alkyl chains in the periphery of the aromatic core. Selected examples of extended trimers substituted with alkyl or alkoxyl chains, which were obtained by cyclotrimerization of arynes, are shown in Figure 4. For example, Pd-catalyzed cyclotrimerization of dialkoxynaphthynes 53a,b led to the isolation of hexaalkoxytrinaphthylenes (substituted [7]starphenes) 54a,b in moderate yields.30 Similarly, it was reported that Cu-catalyzed cyclotrimerization of naphthyne 53c afforded hexabutyl[7]starphene 54c.31 It should be mentioned that this method to synthesize starphenes represents an interesting alternative to the frequently used Ni-promoted Yamamoto coupling of orthodibromo arenes.32 For example, by this method Bunz and coworkers were able to access soluble alkyne-substituted hexadecastarphene 56 in 55% yield from dibromopentacene 55 (Scheme 2).33 D


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Accounts of Chemical Research Scheme 2. Synthesis of Alkyne-Substituted Hexadecastarphene 56 by Ni-Promoted Coupling of Pentacene 5533

Scheme 3. Pd-Catalyzed Cocylcotrimerization of Different Arynes

Scheme 4. Pd-Catalyzed Co-cylcotrimerization of Arynes with Alkynes36

The cyclotrimerization of unsubstituted polycyclic arynes to obtain planar extended triphenylenes is also possible. The [2 + 2 + 2] cycloaddition of naphthyne 68 afforded [7]starphene 69 (Figure 5), which was used as a single molecule logic gate.38 The cyclotrimerization of biphenylene-based aryne 70 led to the isolation of polyarene 71,34 which was deposited on hydrogen-passivated Ge(001):H surface to study its reversible Diels−Alder reaction with surface dangling-bond dimers.35 Similarly, trimerization of polycyclic aryne 72 afforded [13]cloverphene 73.36

In 2014, we reported the preparation of the 3-fold symmetric nanographene 75 with 22 fused benzene rings by means of Pd-catalyzed cyclotrimerization of aryne 74 (Figure 5).39 As expected, the extreme insolubility of this compound precluded characterization by conventional methods such as NMR spectroscopy. However, recent advances in single molecule on-surface characterization by atomic force microscopy (AFM) with CO functionalized tips40,41 permitted visualization of nanographene 75 with submolecular resolution on bilayer NaCl on Cu(111). In addition, scanning tunneling E


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Figure 5. Synthesis of planar extended triphenylene derivatives and AFM images of nanographenes 75 and 77. Reproduced with permission from refs 39 (75) and 42 (77). Copyright 2014 and 2018, respectively, Wiley.

Scheme 5. Synthesis of Aryne Precursors 78 and 79

microscopy (STM) allowed the visualization of HOMO and LUMO densities of this molecule.39 More recently, in 2018, we reported the cyclotrimerization of aryne 76, which is a didehydrogenated derivative of [6]starphene(2.2.1), to obtain the dendritic nanographene 77 formed by 19 cata-fused benzene rings distributed in six branches (Figure 5).42 We proposed the trivial name [19]dendriphene to refer to this molecule, which is the largest unsubstituted cata-condensed PAH that has been obtained to date by solution chemistry. This molecule was characterized on surface by combined AFM/STM with CO-functionalized tips on NaCl (2 ML)/Cu(111). In addition, differential conductance spectroscopy showed a transport gap of 4.1 eV, a considerably large value, which is reasonable bearing in mind the presence of nine Clar sextets in this polyarene.

A key issue for the use of this methodology with large derivatives is the efficient preparation of the corresponding aryne precursors (Scheme 5). For example, ortho(trimethylsilyl)aryl triflates 78 and 79, precursors of arynes 74 and 76, respectively, were prepared in one step from bistriflate 80. Selective generation of monoaryne 81 and Diels−Alder reaction with the bay region of perylene (82) followed by in situ oxidation led to the isolation of triflate 78 in 46% yield. 39 By contrast, Pd-catalyzed annulation of monoaryne 81 with iodobinaphthalene 83 afforded triflate 79 in 19% yield.42 Although the yields are in general poor to moderate, the use of this formal bisbenzyne approach allowed for the fast preparation of structurally complex aryne precursors in one single step. F


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Figure 6. On-surface synthesis of a 22-ring nanographene and visualization by AFM. Reproduced with permission from ref 26. Copyright 2018 Royal Society of Chemistry.

Figure 7. On-surface generation and visualization of aryne 74 by AFM. Reproduced with permission from ref 47. Copyright 2015 Nature Publishing Group.

Figure 8. On-surface synthesis of [13]starphene (87) by formal cyclotrimerization of the tetracene-based aryne 88 and STM image of 87 on Ag(111). Reproduced with permission from ref 49. Copyright 2017, The American Chemical Society.

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ON-SURFACE CHEMISTRY Besides the characterization by AFM/STM of insoluble compounds such as nanographenes 75 and 77 (Figure 5), recent advances on surface techniques under ultrahigh vacuum (UHV) conditions offer the possibility of combining solution chemistry reactions, such as the cyclotrimerization of arynes, with on-surface transformations in order to obtain other graphene materials or even address long-standing chemical challenges.43−46 For example, after the deposition of trimer 46 on Au(111), the annealing of the sample at 380 °C induced the cyclo-dehydrogenation of the six pentahelicene moieties of this molecule, leading to the synthesis of nanographene 84 formed by the fusion of 22 benzene rings (Figure 6).26 Another powerful possibility of on-surface chemistry is the selective cleavage of individual chemical bonds by means of a voltage pulse from the STM tip.41,45 This is particularly useful for the generation and characterization of reactive intermediates and elusive molecules. For example, in 2015, we took advantage of this technique to generate aryne 74 by STM tipinduced cleavage of the two C−I bonds of diiodo derivative 85, which was used as on-surface aryne precursor (Figure 7).47 Compound 85 was also prepared by aryne chemistry, in

particular by reaction of triflate 78 with CsF and I2 in solution.48 Curiously, bond order analysis of the AFM images of the aryne 74 generated on NaCl (2 ML)/Cu(111) suggested that a cumulene resonance structure is the dominant one under these conditions (UHV, 5 K), rather than the more conventional alkyne structure. Remarkably, when aryne 74 was generated on Cu(111), it formed strong bonds to the Cu surface, showing that the reactivity of the aryne is preserved even at cryogenic temperatures. The on-surface generation of arynes from dihaloarenes can be employed with a synthetic objective. For example, it was reported that the deposition of dibromotetracene 86 on Ag(111) and subsequent annealing of the sample led to the formation of [13]starphene (87), presumably through the cyclotrimerization of aryne 88 on surface (Figure 8).49 In fact, aryne dimers and tetramers were also detected by STM in the same experiment. This on-surface cyclotrimerization approach is not limited to the preparation of starphenes, since [13]cloverphene 73 was also generated on Au(111) from a dibromo derivative.50 The on-surface approach to obtain trigonal shaped polyaromatics from dihalo derivatives can be compared with the Ni-promoted Yamamoto reaction, which is G


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Accounts of Chemical Research frequently used to synthesize substituted starphenes by solution chemistry.32,33

predoctoral research stays with Prof. M. A. Pericàs (2017, ICIQ) and Prof. A. Fürstner (MPI für Kohlenforschung). His research interests are focused on the development of aryne chemistry and the synthesis of new polyaromatic hydrocarbons.

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CONCLUSIONS AND PERSPECTIVES Historically, aryne cycloadditions have been frequently exploited for the preparation of large and structurally demanding PAHs. In the last years, the application of new methodologies to generate arynes under mild reaction conditions from easily available precursors, together with the introduction of transition metal catalysis to dominate the aryne reactivity, have stimulated the use of arynes in the synthesis of new PAHs. Our group has been very active in this field, initially by the discovery of the first metal-catalyzed reaction in aryne chemistry, the Pd-catalyzed benzyne cyclotrimerization, and then by the application of this [2 + 2 + 2] cycloaddition reaction to synthesize extended triphenylene derivatives and structurally complex PAHs. It is expected that the combination of transition metal complexes with other highly reactive intermediates will facilitate the discovery of new useful synthetic methodologies. More recently, we have been involved in the use of the cyclotrimerization reaction for the preparation of well-defined nanographenes by a bottom-up approach through chemical synthesis. Although the extreme insolubility of planar unsubstituted nanographenes makes the purification and characterization of these graphene molecules a major challenge, the introduction of techniques such as atomic resolution AFM/STM with functionalized tips has allowed the impressive identification and study of these nanographenes. In this respect, the combination of solution chemistry, on-surface synthesis, and atomic resolution AFM/STM is expected to provide remarkable advances in the near future, including the bottom-up preparation of well-defined graphene materials “à la carte”, the generation of elusive and highly reactive molecules or the discovery of new reactions by on-surface chemistry.

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Enrique Guitián received his Ph.D. degree from the University of Santiago de Compostela in 1981 for work in the field of natural product synthesis under the guidance of Prof. L. Castedo. After postdoctoral work at the University of Hannover under the supervision of Prof. Winterfeldt, he continued his career at the University of Santiago de Compostela (Associate Professor, 1985− 1992; Tenured Professor, 1992). In 2019, he received the Distinguished Career Award from the Spanish Royal Society of Chemistry (RSEQ). His main research interests lie in the design of synthetic methods based on pericyclic reactions of arynes and their application to the synthesis of molecular materials. Dolores Pérez completed her Ph.D. in 1991 at the University of Santiago de Compostela (USC) under the guidance of Prof. E. Guitián and Prof. L. Castedo. She was a MEC-Fullbright postdoctoral fellow at UC Berkeley with Prof. K. P. C. Vollhardt (1992−1993) and visiting scientist with. Prof. S. L. Buchwald at MIT (1996). In 1995, she returned to the USC, where she is currently Full Professor of Organic Chemistry. After her pioneering work on the discovery of metal-catalyzed reactions involving arynes, her current research interests are focused on the further development of aryne chemistry to the synthesis of complex polycyclic aromatic systems and nanographenes. In 2011, D. Pérez launched the Center for Research in Biological Chemistry and Molecular Materials (CiQUS), where she is currently Deputy Director. Diego Peña obtained his Ph.D. in Chemistry in 2001 from the University of Santiago de Compostela, under the supervision of Prof. D. Pérez and Prof. E. Guitián. In 2002, he joined the group of Prof. B. L. Feringa (Groningen University) as a Marie Curie Post-Doctoral Fellow working on asymmetric catalysis. In 2004, he moved back to the University of Santiago de Compostela as Ramón y Cajal researcher and became an Associate Professor in 2008. In 2015, he obtained the Full Professor Accreditation, and in 2018 he was awarded the Ignacio Ribas Medal by the Specialized Group on Organic Chemistry of the Spanish Royal Society of Chemistry (RSEQ). At CiQUS, he is working on the development of new synthetic methodologies, the synthesis of large aromatic compounds and nanographenes, and on-surface chemistry.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.accounts.9b00269. Detailed information about reaction conditions and yields of the cyclotrimerizations (PDF)

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ACKNOWLEDGMENTS We are deeply grateful to all of our co-workers and collaborators for their superb work in the last two decades. We acknowledge financial support by Agencia Estatal de Investigació n (Grants MAT2016-78293-C6-3-R and CTQ2016-78157-R), Xunta de Galicia (Centro singular de investigación de Galicia, accreditation 2016−2019, ED431G/ 09), and Fondo Europeo de Desarrollo Regional (FEDER). I.P. thanks Xunta de Galicia and European Union (European Social Fund, ESF) for the award of a predoctoral fellowship.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Dolores Pérez: 0000-0003-0877-5938 Diego Peña: 0000-0003-3814-589X

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Notes

The authors declare no competing financial interest. Biographies

REFERENCES

(1) Chen, L.; Hernandez, Y.; Feng, X.; Mü llen, K. From nanographene and graphene nanoribbons to graphene sheets: chemical synthesis. Angew. Chem., Int. Ed. 2012, 51, 7640−7654. (2) Narita, A.; Wang, X.; Feng, X.; Müllen, K. New advances in nanographene chemistry. Chem. Soc. Rev. 2015, 44, 6616−6643. (3) Ito, H.; Ozaki, K.; Itami, K. Annulative π-Extension (APEX): Rapid Access to Fused Arenes, Heteroarenes, and Nanographenes. Angew. Chem., Int. Ed. 2017, 56, 11144−11164.

Iago Pozo received his B.S. (2014) and M.S. (2015) in Chemistry from the University of Santiago de Compostela (USC). In 2017, he was awarded a predoctoral fellowship from Xunta de Galicia, and he is currently a Ph.D. student at Center for Research in Biological Chemistry and Molecular Materials (CiQUS) under the supervision of Prof. D. Peña and Prof. D. Pérez. He has carried out two H


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(4) Pérez, D.; Peña, D.; Guitián, E. Aryne Cycloaddition Reactions in the Synthesis of Large Polycyclic Aromatic Compounds. Eur. J. Org. Chem. 2013, 2013, 5981−6013. (5) Wu, D.; Ge, H.; Liu, S. H.; Yin, J. Arynes in the synthesis of polycyclic aromatic hydrocarbons. RSC Adv. 2013, 3, 22727−22738. (6) Krüger, J.; García, F.; Eisenhut, F.; Skidin, D.; Alonso, J. M.; Guitián, E.; Pérez, D.; Cuniberti, G.; Moresco, F.; Peña, D. Decacene: on-surface generation. Angew. Chem., Int. Ed. 2017, 56, 11945−11948. (7) Schulz, F.; García, F.; Kaiser, K.; Pérez, D.; Guitián, E.; Gross, L.; Peña, D. Exploring a route to cyclic acenes by on-surface synthesis. Angew. Chem., Int. Ed. 2019, 58, 9038. (8) Peña, D.; Escudero, S.; Pérez, D.; Guitián, E.; Castedo, L. Efficient Palladium-Catalyzed Cyclotrimerization of Arynes: Synthesis of Triphenylenes. Angew. Chem., Int. Ed. 1998, 37, 2659−2661. (9) Guitián, E.; Pérez, D.; Peña, D. Palladium-catalyzed cycloaddition reactions of arynes. Topics in Organometallic Chemistry Tsuji, J., Ed.; Springer Verlag: Weinheim, 2005; Vol. 14, pp 109−146. (10) Peña, D.; Cobas, A.; Pérez, D.; Guitián, E. An efficient procedure for the synthesis of ortho-trialkylsilylaryl triflates: easy access to precursors of functionalized arynes. Synthesis 2002, 1454− 1458. (11) Peña, D.; Pérez, D.; Guitián, E. Cyclotrimerization Reactions of Arynes and Strained Cycloalkynes. Chem. Rec. 2007, 7, 326−333. (12) Guo, C.; Xia, D.; Yang, Y.; Zuo, X. Synthesis of π-Conjugated Benzocyclotrimers. Chem. Rec. 2019, DOI: 10.1002/tcr.201800160. (13) Xie, C.; Liu, L.; Zhang, Y.; Xu, P. Copper-catalyzed alkynearyne and alkyne-alkene-aryne coupling reactions. Org. Lett. 2008, 10, 2393−2396. (14) Chen, L.; Zhang, C.; Wen, C.; Zhang, K.; Liu, W.; Chen, Q. Gold-catalyzed cyclotrimerization of arynes for the synthesis of triphenylenes. Catal. Commun. 2015, 65, 81−84. (15) Wang, Y.; Stretton, A. D.; McConnell, M. C.; Wood, P. A.; Parsons, S.; Henry, J. B.; Mount, A. R.; Galow, T. H. 1,4,5,8,9,12Hexamethyltriphenylene. A Molecule with a Flipping Twist. J. Am. Chem. Soc. 2007, 129, 13193−13200. (16) Iglesias, B.; Peña, D.; Pérez, S.; Guitián, E.; Castedo, L. Palladium-catalyzed Trimerization of Strained Cycloalkynes: Synthesis of Decacyclene. Synlett 2002, 486−488. (17) Cant, A. A.; Roberts, L.; Greaney, M. F. Generation of benzyne from benzoic acid using C−H activation. Chem. Commun. 2010, 46, 8671−8673. (18) García-López, J.; Greaney, M. F. Use of 2-Bromophenylboronic Esters as Benzyne Precursors in the Pd-Catalyzed Synthesis of Triphenylenes. Org. Lett. 2014, 16, 2338−2341. (19) Lin, J. B.; Shah, T. K.; Goetz, A. E.; Garg, N. K.; Houk, K. N. Conjugated Trimeric Scaffolds Accessible from Indolyne Cyclotrimerizations: Synthesis, Structures, and Electronic Properties. J. Am. Chem. Soc. 2017, 139, 10447−10455. (20) Tozawa, H.; Kakuda, T.; Adachi, K.; Hamura, T. Star-Shaped Polycyclic Aromatic Ketones via 3-Fold Cycloadditionsof Isobenzofuran Trimer Equivalent. Org. Lett. 2017, 19, 4118−4121. (21) Peña, D.; Pérez, D.; Guitián, E.; Castedo, L. Synthesis of Hexabenzotriphenylene and Other Strained Polycyclic Aromatic Hydrocarbons by Palladium-Catalyzed Cyclotrimerization of Arynes. Org. Lett. 1999, 1, 1555−1557. (22) Peña, D.; Cobas, A.; Pérez, D.; Guitián, E.; Castedo, L. Kinetic Control in the Palladium-Catalyzed Synthesis of C2-Symmetric Hexabenzotriphenylene. A Conformational Study. Org. Lett. 2000, 2, 1629−1632. (23) Peña, D.; Cobas, A.; Pérez, D.; Guitián, E.; Castedo, L. Dibenzo[a,o]phenanthro[3,4-s]pycene, a Configurationally Stable Double Helicene: Synthesis and Determination of Its Conformation by NMR and GIAO Calculations. Org. Lett. 2003, 5, 1863−1866. (24) Romero, C.; Peña, D.; Pérez, S.; Guitián, E. PalladiumCatalyzed [2 + 2 + 2] Cycloadditions of 3,4-Didehydrophenanthrene and 1,2-Didehydrotriphenylene. J. Org. Chem. 2008, 73, 7996−8000. (25) Hosokawa, T.; Takahashi, Y.; Matsushima, T.; Watanabe, S.; Kikkawa, S.; Azumaya, I.; Tsurusaki, A.; Kamikawa, K. Synthesis, Structures, and Properties of Hexapole Helicenes: Assembling Six I


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Accounts of Chemical Research (44) Lindner, R.; Kühnle, A. On-surface reactions. ChemPhysChem 2015, 16, 1582−1592. (45) Peña, D.; Pavliček, N.; Schuler, B.; Moll, N.; Pérez, D.; Guitián, E.; Meyer, G.; Gross, L. Addressing long-standing chemical challenges by AFM with functionalized tips. On-surface synthesis II; de Oteyza, D. G., Rogero, C. Eds.; Springer, 2018; pp 209−227. (46) Clair, S.; de Oteyza, D. G. Controlling a chemical coupling reaction on a surface: tools and strategies for on-surface synthesis. Chem. Rev. 2019, 119, 4717−4776. (47) Pavliček, N.; Schuler, B.; Collazos, S.; Moll, N.; Pérez, D.; Guitián, E.; Meyer, G.; Peña, D.; Gross, L. On-surface generation and imaging of arynes by atomic force microscopy. Nat. Chem. 2015, 7, 623−628. (48) Rodríguez-Lojo, D.; Cobas, A.; Peña, D.; Pérez, S.; Guitián, E. Aryne Insertion into I-I σ-Bonds. Org. Lett. 2012, 14, 1363−1365. (49) Sanchez-Sánchez, C.; Nicolaï, A.; Rossel, F.; Cai, J.; Liu, J.; Feng, X.; Müllen, K.; Ruffieux, P.; Fasel, R.; Meunier, V. On-Surface Cyclization of ortho-Dihalotetracenes to Four- and Six Membered Rings. J. Am. Chem. Soc. 2017, 139, 17617−17623. (50) Fan, Q.; Werner, S.; Tschakert, J.; Ebeling, D.; Schirmeisen, A.; Hilt, G.; Hieringer, W.; Gottfried, J. M. Precise Monoselective Aromatic C−H Bond Activation by Chemisorption of Meta-Aryne on a Metal Surface. J. Am. Chem. Soc. 2018, 140, 7526−7532.

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Synthesis of Nanographenes, Starphenes, and Sterically Congested

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