Pnictogen‐Bonding Catalysis: An Interactive Tool to Uncover Unorthodox Mechanisms in Polyether Cascade Cyclizations

• Published in: Chemistry : a European journal Vol. 26; no. 67; pp. 15471 - 15476
• Main Authors: Paraja, Miguel, Gini, Andrea, Sakai, Naomi, Matile, Stefan
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.12.2020
• Subjects: Bonding; Brevetoxins; cascade reactions; Catalysis; Catalysts; Chemistry; Cyclization; epoxide-opening polyether cyclizations; Epoxides; Epoxy Compounds - chemistry; Inversion; Lewis acid; Molecular Conformation; pnictogen-bonding catalysis; polyether natural products; Ring opening; Stereoselectivity; σ-hole catalysis; cascade reactions; σ-hole catalysis; epoxide-opening polyether cyclizations; pnictogen-bonding catalysis; polyether natural products
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202003426

Pnictogen‐bonding catalysis and supramolecular σ‐hole catalysis in general is currently being introduced as the non‐covalent counterpart of covalent Lewis acid catalysis. With access to anti‐Baldwin cyclizations identified as unique characteristic, pnictogen‐bonding catalysis appeared promising to elucidate one of the hidden enigmas of brevetoxin‐type epoxide opening polyether cascade cyclizations, that is the cyclization of certain trans epoxides into cis‐fused rings. In principle, a shift from SN2‐ to SN1‐type mechanisms could suffice to rationalize this inversion of configuration. However, the same inversion could be explained by a completely different mechanism: Ring opening with C−C bond cleavage into a branched hydroxy‐5‐enal and the corresponding cyclic hemiacetal, followed by cascade cyclization under conformational control, including stereoselective C−C bond formation. In this report, a pnictogen‐bonding supramolecular SbV catalyst is used to demonstrate that this unorthodox polyether cascade cyclization mechanism occurs. One of the hidden enigmas of natural‐product inspired epoxide‐opening polyether cascade cyclizations is the inversion of configuration from trans epoxides to cis‐fused endo products. Here, pnictogen‐bonding catalysis is introduced as an interactive tool to find the answer with an unorthodox mechanism centered around an acyclic, achiral hydroxy‐5‐enal intermediate, produced by C−C bond cleavage, then cyclized by stereoselective C−C bond formation.