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Updated: Jun 10, 2025

Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes
Published on: April 1, 2013
Steric Activation in the Nazarov Cyclization of Fully Substituted Divinyl Ketones
Shuqi Chen1, Angus B Keto2, Ahmad El-Hawli1
1Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Abstract:
Fully substituted divinyl ketones (fsDVKs) have long been regarded as resistant to Nazarov cyclization (NC) unless they contain strategically positioned electronically activating substituents. Here, however, we show that fsDVKs bearing only electronically neutral alkyl or aryl groups actually undergo facile NC due to steric crowding in the pentadienyl cation intermediate, which raises its energy and reduces the barrier height to cyclization. Strongly ionizing and suitably bulky acid moieties further increase the energy of this intermediate cation, favoring cyclization. These features enable NCs of fsDVKs to be employed in the ready construction of multiple contiguous all-carbon quaternary stereocenters under mild conditions, in the absence of electronically activating groups.
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