Open AccessBrønsted-Acid-Catalyzed Intramolecular Carbonyl–Olefin Reactions: Interrupted Metathesis vs Carbonyl-Ene Reaction
Author(s) -
Tanmay Malakar,
Paul M. Zimmerman
Publication year - 2021
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.0c03021
Subject(s) - chemistry , intramolecular force , ene reaction , oxetane , brønsted–lowry acid–base theory , catalysis , triflic acid , medicinal chemistry , olefin fiber , electrophile , photochemistry , stereochemistry , organic chemistry
Lewis acid catalysts have been shown to promote carbonyl-olefin metathesis through a critical four-membered-ring oxetane intermediate. Recently, Brønsted-acid catalysis of related substrates was similarly proposed to result in a transient oxetane, which fragments within a single elementary step via a postulated oxygen-atom transfer mechanism. Herein, careful quantum chemical investigations show that Brønsted acid (triflic acid, TfOH) instead invokes a mechanistic switch to a carbonyl-ene reaction, and oxygen-atom transfer is uncompetitive. TfOH's conjugate base is also found to rearrange H atoms and allow isomerization of the carbocations that appear after the carbonyl-ene reaction. The mechanism explains available experimental information, including the skipped diene species that appear transiently before product formation. The present study clarifies the mechanism for activation of intramolecular carbonyl-olefin substrates by Brønsted acids and provides important insights that will help develop this exciting class of catalysts.