SYNLETT0936-52141437-2096 © Georg Thieme Verlag Stuttgart · New York 2015, 26, A–AB A account Syn lett T. Hensel et al. Account Synthesis of Heterocyclic [8]Circulenes and Related Structures Thomas Hensel Nicolaj N. Andersen Malene Plesner Michael Pittelkow* Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark [email protected] Received: 09.08.2015 1 Introduction Accepted after revision: 29.09.2015 Published online: DOI: 10.1055/s-0035-1560524; Art ID: st-2015-a0625-a [n]Circulenes (Figure 1) are fully conjugated polycyclic compounds that can formally be derived from the alicyclic Abstract In this account we give an overview of the synthesis and [n]radialenes by connecting the termini of the semicyclic properties of heterocyclic [8]circulenes. Much of the interest in study- double bonds by etheno bridges.1 Another way to view the ing heterocyclic [8]circulenes stems from the planar cyclooctatetraene core often contained in these compounds, which in principle is antiaro- [n]circulenes is as a class of compounds that are character- matic. We start with a short introduction to the hydrocarbon [n]circu- ized by having a central ring with [n] sides surrounded by a lenes and proceed to describe the synthetic chemistry involved in creat- band of ortho-fused benzene rings. ing tetraoxa[8]circulenes, with particular focus on the acid-mediated The largest [n]circulene that has been synthesized is oligomerization of benzo- or naphthoquinones, resulting in some sim- ple rules for predicting the outcome of the oligomerization reactions. [8]circulene (6) as a π-extended derivative, and the largest These rules have guided the synthetic strategies for the preparation of [n]circulene that has been described computationally is azatrioxa[8]circulenes and diazadioxa[8]circulenes, which will be de- [20]circulene.1a As [3]radialene is known, one might expect scribed in separate sections of this account. More traditional synthetic that [3]circulene would exist as well, but so far the synthe- strategies have been applied in the preparation of octathia[8]circulene, sized [n]circulenes only span the bowl-shaped [4]circulene tetrathiatetraselena[8]circulene, and a number of other heterocyclic [8]circulenes, and these synthetic efforts will be highlighted. Finally, a 2 and [5]circulene 3, the planar [6]circulene 4 and the sad- section describing structures that are closely related to the heterocyclic dle-shaped [7]circulene 5 and [8]circulene 6 (Figure 1). In a [8]circulenes will be presented, and at the end we will comment on the computational study, Hopf and co-workers predicted the Downloaded by: Koebenhavns Universitetsbibliotek. Copyrighted material. extensive theoretical work regarding the question of aromaticity/anti- geometries of all hydrocarbon [n]circulenes from the [3]cir- aromaticity of the central cyclooctatetraene of heterocyclic[8]circu- culene 1 to [20]circulene.1a They described the strain ener- lenes. 1 Introduction gy associated with enlarging the [n]circulene structure as 2 Synthesis of [n]circulenes compared to the energy associated with [6]circulene 4. The 2.1 [4]Circulene larger structures become helical, as predicted by density 2.2 [5]Circulene functional theory (DFT) calculations. The existence of a 2.3 [6]Circulene [3]circulene is considered unfeasible. 2.4 [7]Circulene 2.5 [8]Circulene Heterocyclic circulenes are [n]circulenes where one or 3 Synthesis of Tetraoxa[8]circulenes: A Historical Perspective more of the etheno bridge(s) have been replaced with a he- 4 Synthesis of Azatrioxa[8]circulenes teroatom such as oxygen, sulfur, nitrogen, or selenium. 5 Synthesis of Diazadioxa[8]circulenes Some of the known hetero[8]circulenes (substituents not 6 Synthesis of Other Heterocyclic [8]Circulenes 7 Synthesis of Structurally Related Compounds shown) are presented in Figure 2. The slightly different ge- 8 Hetero[8]circulenes and Related Compounds as Tools to Study ometries of furan, thiophene, pyrrole, and other five-mem- Aromaticity and Antiaromaticity bered 6π-aromatic systems as compared to benzene make 9 Conclusion and Outlook the heterocyclic [8]circulenes very different from hydrocar- bon [8]circulenes, both in their geometry and chemical and Key words circulenes, heterocycles, aromaticity, antiaromatcity, syn- thesis, geometry, cyclooctatetraenes, nucleus-independent shifts physical properties. The relationship between the struc- tures of circulenes and the geometries of these compounds © Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, A–AB B Syn lett T. Hensel et al. Account has attracted significant interest.1 The emergence of non- whether the circulene is planar or bowl-shaped as shown in planar, fully conjugated systems, such as the fullerenes and Figure 3. We believe that Dopper and Wynberg’s model falls carbon nanotubes, has certainly served as an inspiration for short in its ability to predict saddle-shaped circulenes, as it studies of the fundamental properties of non-planar circu- can be difficult to define an outer radius of a saddle. We lenes.2 In an early study, Dopper and Wynberg introduced a therefore propose an alternative model in which the wedge simple yet efficient approach for analyzing the geometry of angles of the aromatic moieties are summed, as shown in circulenes using a mathematical model containing the in- Figure 4. This model was inspired by considerations from 4 ner (r1) and outer (r2) radii of the circulene, and the length Högberg’s doctoral thesis. The wedge angles are derived of the spokes (a).3 From this model, it is possible to assess from literature DFT calculations5 using the C–C–C bonding quickly, without the need of computational modelling, angle of the cyclic compounds. Comparing the sum of the Biographical Sketches Thomas Hensel received his gree was carried out in Michael the Department of Chemistry, M.Sc. degree from Leipzig Uni- Pittelkow’s group at the Univer- University of Copenhagen, versity in 2012. Supported by sity of Copenhagen. He is cur- working on the synthesis and the Erasmus program, the prac- rently a Ph.D. student under the applications of novel hetero- tical work of the master’s de- direction of Michael Pittelkow at [8]circulenes. Nicolaj Nylandsted Anders- pervision of Michael Pittelkow. tin[6]urils, again under the en was born in 1991 on the is- During his bachelor’s and mas- supervision of Michael Pittel- land of Funen, Denmark. He ter’s studies, he has been devel- kow. He was a recipient of the completed his B.Sc. in 2013 and oping helicene chemistry with Novo Scholarship Programme in his M.Sc. in 2015 at the Depart- possible applications in DNA 2014. ment of Chemistry, University recognition. He is currently pur- of Copenhagen under the su- suing a Ph.D., working with bio- Malene Plesner was born in John Nielsen. In 2014, she com- tion of different azatrioxa[8]cir- Copenhagen in 1989. She stud- pleted her M.Sc. degree super- culenes. She is currently Downloaded by: Koebenhavns Universitetsbibliotek. Copyrighted material. ied chemistry at the University vised by Michael Pittelkow teaching high school chemistry of Copenhagen and received within the field of synthetic or- at Johannesskolen, Copenha- her B.Sc. degree in 2012 under ganic chemistry, focusing on gen. the supervision of Professor the synthesis and characteriza- Michael Pittelkow was born Australia (CSIRO in Melbourne, Professor Jeremy K. M. Sanders in Brøndby Strand, near Copen- with Dr. Kevin Winzenberg), The before moving back to the Uni- hagen. He studied chemistry at Netherlands (The Technical Uni- versity of Copenhagen. In 2013, the University of Copenhagen versity of Eindhoven, with Pro- he became an associate profes- where he received his Ph.D. de- fessor E. W. Meijer) and the U.K. sor. His research interests in- gree in 2006 under the supervi- (University of Cambridge). He clude organic synthesis, sion of Associate Professor Jørn undertook postdoctoral train- physical organic chemistry, dy- B. Christensen. During his stud- ing at the University of Cam- namic combinatorial chemistry ies he spent extended periods in bridge under the mentorship of and supramolecular chemistry. © Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, A–AB C Syn lett T. Hensel et al. Account wedge angles, Σ∠, one intuitively expects circulenes with Σ∠ S S Se Se S S values close to 360° to be planar, whereas lower Σ∠ indicate bowls and higher Σ∠ saddles. S S S S (a) Se Se S S S S 6 7 8 [8]circulene tetrathiatetraselena[8] octathia[8] S Se O radialene scaffold band of ortho-fused with etheno bridges benzene rings S S Se Se O O (b) S Se O 9 10 11 tetrathia[8] tetraseleno[8] tetraoxa[8] 12 3 H H [3]circulene [4]circulene [5]circulene N N unknown derivate known corannulene bowl-shaped known bowl-shaped O O O O O N H 12 13 14 azatrioxa[8] diazadioxa[8] tetramethano[8] 45 6 Figure 2 Structures of synthetically available heterocyclic [8]circu- [6]circulene [7]circulene [8]circulene lenes. The core structures are shown without substituents coronene known derivative known known saddle-shaped saddle-shaped planar scription of the synthetic work developed for the syntheses Figure 1 Structures of [n]circulenes. (a) [n]Circulenes may be viewed as derivatives of [n]radialenes or as rings of ortho-fused benzene rings. of heterocyclic [8]circulenes. We will devote special em- (b) Geometries of [n]circulenes phasis on the early work developed by Erdtman and Hög- berg on the preparation of tetraoxa[8]circulenes and how the mindset developed in their work has inspired our syn- By comparing 15 circulenes,3,6 we found that planar cir- theses of azatrioxa- and diazadioxa[8]circulenes. We will culenes indeed reside in a narrow interval between 336° also describe the synthetic efforts in developing other types and 380°.