Enantioselective Tail‐to‐Head Terpene Cyclizations by Optically Active Hexameric Resorcin[4]arene Capsule Derivatives

Abstract

Molecular capsules enable the conversion of substrates inside a closed cavity, mimicking to some extent enzymatic catalysis. Chirality transfer from the molecular capsule onto the encapsulated substrate has been only studied in a few cases. Here we demonstrate that chirality transfer is possible inside a rather large molecular container of approximately 1400 Å 3 . Specifically, we present 1) the first examples of optically active hexameric resorcin[4]arene capsules, 2) their ability to enantioselectively catalyze tail-to-head terpene cyclizations, and 3) the surprisingly high sensitivity of enantioselectivity on the structural modifications.

Decoded fingerprints of hyperresponsive, expanding product space: polyether cascade cyclizations as tools to elucidate supramolecular catalysis

“…One general expectation from supramolecular catalysis 1–10 is that new ways to interact will provide new ways to transform on the molecular level. This translates to access to new reactivity and products, at best contributing to new solutions for otherwise persistent challenges in science and society.…”

“…2d). 3,4 Their internal surface offers hydrogen-bond donors and π-basic aromatic planes for catalysis within their confined interior. 3,4 Unique selectivities have been reported, also for bioinspired terpene cyclizations, for instance.…”

“…3,4 Their internal surface offers hydrogen-bond donors and π-basic aromatic planes for catalysis within their confined interior. 3,4 Unique selectivities have been reported, also for bioinspired terpene cyclizations, for instance. 4 From cascade cyclization with the mixture of cis - 1 diastereomers in capsules 8 , cis -(BA)- 3 was obtained as the main product besides the still preferred cis -(BB)- 2 (Fig.…”

“…Stabilization of carbocations via cation–π interactions is a distinct feature of this type of capsules. 3,4…”

Impact of Host Flexibility on Selectivity in a Supramolecular Host-Catalyzed Enantioselective aza-Darzens Reaction

“…In asymmetric catalysis mediated by small molecules, flexibility is now frequently cited as a crucial factor in enhancing selectivity, and efforts have been made to engineer more flexible scaffolds . Work from our lab has highlighted the importance of scaffold flexibility in facilitating NCIs in asymmetric catalysis. , In addition, peptide-based catalysts and hydrogen-bond-donating catalysts highlight the enantioselectivity that can be achieved when flexibility is incorporated into catalyst backbones. − Asymmetric catalysis mediated by supramolecular cages could be an excellent way to scrutinize the effect of cage flexibility on reaction outcome; however, the field of supramolecular asymmetric catalysis remains underdeveloped. , Many enantiopure hosts rely on the incorporation of already high-performing small molecule catalysts. − Because of this, the selectivity observed in the majority of these systems is intrinsic to the small molecule catalyst, not to the overall supramolecular scaffolding. There are few enantiopure supramolecular hosts that enable enantioselective catalysis in the absence of an already high-performing small molecule ligand. − In the systems reported herein, enantioinduction is a product of supramolecular chirality, presenting an opportunity to systematically explore the role of flexibility on the reactions occurring in this chiral space.…”