Brønsted Acid Catalyzed Dearomatization by Intramolecular Hydroalkoxylation/Claisen Rearrangement: Diastereo‐ and Enantioselective Synthesis of Spirolactams

• Published in: Angewandte Chemie International Edition Vol. 60; no. 52; pp. 27164 - 27170
• Main Authors: Chen, Peng‐Fei, Zhou, Bo, Wu, Peng, Wang, Binju, Ye, Long‐Wu
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 20.12.2021; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: alkynes; Aromatic compounds; Atom economy; Brønsted acids; Catalysis; Chemistry; Chemistry, Multidisciplinary; cyclizations; Enantiomers; heterocycles; Heterocyclic compounds; kinetic resolution; Nucleotide sequence; Phosphoric acid; Physical Sciences; Science & Technology; Substrates; ASYMMETRIC-SYNTHESIS; HYDROGENATION; alkynes; OXINDOLES; CLAISEN REARRANGEMENT; INDOLES; cyclizations; YNAMIDES; REDUCTION; heterocycles; kinetic resolution; INHIBITORS; Bronsted acids; ACCESS; Brønsted acids
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202113464

Described herein is a novel Brønsted acid catalyzed intramolecular hydroalkoxylation/Claisen rearrangement, allowing the practical and atom‐economic synthesis of a range of valuable spirolactams from readily available ynamides in generally good to excellent yields with excellent diastereoselectivities and broad substrate scope. Importantly, an unexpected dearomatization of nonactivated arenes and heteroaromatic compounds is involved in this tandem sequence. Moreover, an asymmetric version of this tandem cyclization was also achieved by efficient kinetic resolution by chiral phosphoric acid catalysis. In addition, the [3,3]‐rearrangement is shown to be kinetically preferred over the related [1,3]‐rearrangement by theoretical calculations. A Brønsted acid catalyzed intramolecular hydroalkoxylation/Claisen rearrangement is disclosed that involves an unexpected dearomatization of nonactivated arenes and heteroaromatic compounds and allows the practical and atom‐economic synthesis of various valuable spirolactams. Moreover, the asymmetric version of this tandem cyclization is also achieved via kinetic resolution by chiral phosphoric acid catalysis.