Expanded Helicenes as Synthons for Chiral Macrocyclic Nanocarbons

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 configurational 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.

By-design molecular architecturesviaalkyne metathesis

“…2b). In 2019, Tilley and co-workers reported such an example in the synthesis of macrocycle 4, where the byproduct, 4-octyne, could be trapped by 5Å MS. 39,40 Compared with propyne, 1-pentyne is a liquid that is much easier to handle quantitatively, also with a higher solubility. The 1-pentynyl group could be installed via Sonogashira coupling reaction, which is robust as well as selective toward different halides.…”

“…5b). 40 The expanded helicene macrocycle 18 crystalizes in supramolecular helices with the uncommon, non-centrosymmetric space group P6 4 22, where all the molecules are homochiral. When crystallizing out from the solution phase, the two helical structures with opposite handedness (PP/MM) could form a double helix superstructure, in which the shortest p-stacking distance (3.5Å) enhances the stability of the superstructure.…”

Elucidation of Diverse Solid‐State Packing in a Family of Electron‐Deficient Expanded Helicenes via Microcrystal Electron Diffraction (MicroED)**

“…One exception is dimeric [13]helicene 1 b‐Dim (Figure 1 a), [9a] wherein each helicene displays a large pitch (7.4 Å) to accommodate extensive π‐stacking. Another case where a notable molecular distortion was observed in the crystal structure was for the recently‐reported Figure‐eight expanded helicene dimer [9c] . There, an intricate network of π‐stacking interactions appears to be the driving force for the distortion.…”

“…The parent, electron‐rich helicene 1 a crystallized in the chiral P 2 1 2 1 2 1 space group, wherein the constituent molecules are homochiral and form weakly bound columns (Figure 2 a). This is the second example of a homochiral expanded helicene crystal structure, [9c] and it is notable since 1 a is expected to have an extremely low enantiomerization barrier in solution [9a‐c] . The closest π‐stacking distance is 3.8 Å, and there are only two overlapping rings.…”

“…In contrast, no aggregation was apparent for the [11]helicene analogue ( 1 a ). Subsequently, the covalent linkage of two expanded helicenes afforded a configurationally labile “Figure‐eight” dimer that crystallized into an intricate homochiral network containing two distinct yet interconnected helical superstructures [9c] …”