pubs.acs.org/JACS Article Expanded Helicenes as Synthons for Chiral Macrocyclic Nanocarbons Gavin R. Kiel, Katherine L. Bay, Adrian E. Samkian, Nathaniel J. Schuster, Janice B. Lin, Rex C. Handford, Colin Nuckolls, K. N. Houk, and T. Don Tilley* Cite This: J. Am. Chem. Soc. 2020, 142, 11084−11091 Read Online ACCESS Metrics & More Article Recommendations *sı Supporting Information ABSTRACT: Expanded helicenes are large, structurally flexible π- frameworks that can be viewed as building blocks for more complex chiral nanocarbons. Here we report a gram-scale synthesis of an alkyne- functionalized expanded [11]helicene and its single-step transformation into two structurally and functionally distinct types of macrocyclic derivatives: (1) a figure-eight dimer via alkyne metathesis (also gram scale) and (2) two arylene-bridged expanded helicenes via Zr-mediated, formal [2+2+n] cycloadditions. The phenylene-bridged helicene displays a substantially higher enantiomerization barrier (22.1 kcal/ mol) than its helicene precursor (<11.9 kcal/mol), which makes this a promising strategy to access configurationally stable expanded helicenes. In contrast, the topologically distinct figure-eight retains the configura- tional lability of the helicene precursor. Despite its lability in solution, this compound forms homochiral single crystals. Here, the configuration is stabilized by an intricate network of two distinct yet interconnected helical superstructures. The enantiomerization mechanisms for all new compounds were probed using density functional theory, providing insight into the flexibility of the figure-eight and guidance for future synthetic modifications in pursuit of non-racemic macrocycles. ■ INTRODUCTION oligomeric or polymeric structures (i.e., where they are not part of the same PAH framework) has also yielded interesting There is a rapidly growing appreciation that chirality endows 7 conjugated nanocarbons and related polycyclic aromatic results. For example, Di Bari and Diedrich demonstrated that “ photophysical and chiroptical properties can be significantly hydrocarbons (PAHs) with novel photophysical ( chiropti- 7a 1 enhanced in an oligomeric structure and Yamaguchi has Downloaded via COLUMBIA UNIV on July 24, 2020 at 20:38:37 (UTC). cal”), electronic, and supramolecular properties. Thus, developed numerous helicene oligomers (e.g., C) that exhibit a chirality is an orthogonal design element for diverse 7b,c applications in molecular nanotechnology (e.g., machines and range of complex self-assembly phenomena. Notably, many switches) and organic electronics.2 Chiral nanocarbons occupy of these self-assembling oligomers are macrocyclic. Other See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. ff helicene-containing macrocycles possess fascinating molecular a vast chemical space, and tremendous e ort has been devoted 7d−j 1−3 topologies. Along these lines, a few groups isolated figure- to their synthesis and evaluation. Constraining a nano- eight dimers constructed from [5]helicenes (e.g., D) or their carbon into a macrocyclic framework is a common way to − heterocyclic analogues7d f and Isobe synthesized an analogous introduce chirality into an otherwise achiral structure, and fi dimer of [4]helicene (E), which is a molecular manifestation of might provide a means to increase the con gurational stability 7g 4 Penrose’s illusory never-ending staircase. Finally, there have in those that are inherently chiral. More importantly, new been two instances of macrocyclic [5]helicene trimers that properties can emerge in a macrocyclic environment as a result ̈ display Mobius topology. Durola and Herges reported D3- of its impact on molecular topology and spatial orientation of 7h 4,5 symmetrical trimer F, for which a rare “triply-twisted” constituent units. topology gives rise to Möbius aromaticity (the C isomer was As the prototypical chiral PAHs, carbohelicenes (A, Figure 2 1a) are natural building blocks for more complex chiral nanocarbons. Fusion of more than one helicene into a Received: March 23, 2020 contiguous PAH framework gives rise to “multiple helicenes” Published: May 26, 2020 (e.g., B),6 which exhibit unique solid-state behavior as a result of their contorted6b structures (e.g., formation of host−guest complexes with acceptor molecules6d and π-stacking in three dimensions6e). Introduction of helicenes into “non-fused” © 2020 American Chemical Society https://dx.doi.org/10.1021/jacs.0c03177 11084 J. Am. Chem. Soc. 2020, 142, 11084−11091 Journal of the American Chemical Society pubs.acs.org/JACS Article Figure 1. (a) Examples of chiral nanocarbons derived from carbohelicene building blocks. (b) New chiral macrocyclic nanocarbons (1 and 2) derived from an expanded helicene (this work). Δ ⧧ also isolated). While the current manuscript was under review, experimentally validated due to their low G enant values. 7i Δ ⧧ fi Moore, Zhu, and Garcia-Garibay reported trimer G, which Thus, strategies to increase G enant are of signi cant interest. ff di ers from F based on its ethynyl spacers and C2 symmetry. This contribution describes a scalable and divergent In 2017, the Tilley group introduced a new class of chiral synthetic route to two structurally and functionally distinct nanocarbons, the “expanded helicenes” (H, Figure 1b), which chiral macrocyclic nanocarbons (1 and 2, Figure 1b) from a fi have larger cavities and diameters than A as a result of single expanded helicene building block. The rst, a geometri- 8 cally constrained “arylene-bridged” expanded helicene (1), alternating angular and linear ring-fusion. With the aid of a ff fi general, [2+2+n] cycloaddition strategy, these compounds provides an e ective platform to increase con gurational stability, which is an important step toward interrogation of were shown to exhibit unique self-assembly (e.g., a π-stacked expanded helicene chiroptical properties. The second, a double helix) and low enantiomerization free energy barriers fi Δ ⧧ fl topologically distinct gure-eight arylene ethynylene macro- ( G enant), both resulting from their conformationally exible 2 fl fl cycle ( ), retains the exibility and conformational lability of backbones. Such exibility was more recently observed and its helicene precursor, which appears to facilitate its unique studied computationally for an unsubstituted example by crystal packing. An important step toward accessing 1 and 2 9 Matsuda and co-workers. These authors also suggested that was development of a simple, gram-scale synthesis of the this class of molecules will possess exceptional chiroptical helicene precursor 3 (Scheme 1), which contains alkynyl properties (e.g., strong excitation dissymmetry factors) as a groups at its termini. This was enabled by application of a result of their larger diameters, but this has not yet been recently discovered,10 site-selective [2+2+2] reaction. The 11085 https://dx.doi.org/10.1021/jacs.0c03177 J. Am. Chem. Soc. 2020, 142, 11084−11091 Journal of the American Chemical Society pubs.acs.org/JACS Article Scheme 1. Gram-Scale Synthesis of Alkynylated Expanded preserved alkynyl groups at the termini of 3 undergo a formal [11]Helicene 3 [2+2+n] cycloaddition (two examples) and alkyne metathesis to give 1 and 2, respectively (Scheme 2). Importantly, the orthogonality of these transformations makes them amenable to a rapid, one-pot process. ■ RESULTS AND DISCUSSION The synthesis of alkynylated expanded helicene 3 (Scheme 1) was accomplished in three steps from phenanthrene dibromide 4. The previously reported procedure8 for 4 proved to be highly scalable, providing routine access to 35−40 g of this compound. Treatment of 4 with 1.0 equiv of nBuLi resulted in a selective monolithiation via lithium−bromine exchange, giving 5 after a MeOH quench.10 The reaction of 5 with iPrMgCl·LiCl gave an in situ-generated Grignard reagent that was Kumada cross-coupled with 4 to give hexa(alkynyl)- terphenanthrene 6 in 70% yield. Subjection of 6 to the previously developed,8,10,11 Ir-catalyzed [2+2+2] cycloaddition conditions afforded the desired helicene 3 in excellent yield (isolated: 80%; 1H NMR: 88%). Notably, high dilution is not necessary for preservation of the reactive alkynyl groups (100 mM diyne concentration), which enabled the synthesis of 3 on a gram scale. Furthermore, helicene 3 was stable even when it was re-subjected (after isolation) to more forcing [2+2+2] conditions (10 equiv monoyne, 12% Ir(COD)(dppe)Cl, 105 ° C in toluene-d8), and the three-site [2+2+2] product (7) was not observed. Scheme 2. Divergent Macrocyclization of Helicene 3 to Form Arylene-Bridged Helicenes 1 and Figure-Eight Dimer 2 11086 https://dx.doi.org/10.1021/jacs.0c03177 J. Am. Chem. Soc. 2020, 142, 11084−11091 Journal of the American Chemical Society pubs.acs.org/JACS Article The spatial orientation of the alkynyl groups in 3 suggested Both types of macrocycles can also be accessed in a one-pot the possibility of a formal [2+2+n] cycloaddition to form the procedure from hexayne 6, as demonstrated by the synthesis of conformationally restricted, “bridged-helicene” structure 1 1-Benz and 2 in 51 and 77% yields, respectively. These yields (Scheme 2).12 Since the analogous 7 did not form under Ir are comparable to those from the two-step procedures outlined catalysis (see above), we turned to a more reactive, low-valent above. Furthermore, 1.2 g of the figure-eight macrocycle (2) was zirconocene reagent. Upon treatment of a solution of helicene isolated using this one-pot approach. 3 in benzene-d6 with 1.2 equiv of Cp2Zr(pyr)(Me3SiC The new compounds are highly soluble in common aromatic 13 CSiMe3), the intermediate zirconacyclopentadiene-bridged and chlorinated solvents and insoluble in more polar and non- helicene 1-Zr was observed in 86% yield by 1H NMR polar solvents. The 1H NMR chemical shifts of 1-Se, 2, and 3 spectroscopy. Zirconacyclopentadienes are typically isolable, in chloroform-d are independent of concentration (see Figures but they are most conveniently generated in situ as synthetic S13−S15), suggesting that their high solubility results from intermediates.