page_title: Nazarov cyclization reaction
section_title: Classical Nazarov cyclizations
hierarchical_section_title: Nazarov cyclization reaction / Classical Nazarov cyclizations
caption_attribution_description: English: synthesis of Nor Stereopolide
context_page_description: The Nazarov cyclization reaction is a chemical reaction used in organic chemistry for the synthesis of cyclopentenones. The reaction is typically divided into classical and modern variants, depending on the reagents and substrates employed. It was originally discovered by Ivan Nikolaevich Nazarov in 1941 while studying the rearrangements of allyl vinyl ketones.
  As originally described, the Nazarov cyclization involves the activation of a divinyl ketone using a stoichiometric Lewis acid or protic acid promoter. The key step of the reaction mechanism involves a cationic 4π-electrocyclic ring closure which forms the cyclopentenone product. As the reaction has been developed, variants involving substrates other than divinyl ketones and promoters other than Lewis acids have been subsumed under the name Nazarov cyclization provided that they follow a similar mechanistic pathway.
  The success of the Nazarov cyclization as a tool in organic synthesis stems from the utility and ubiquity of cyclopentenones as both motifs in natural products and as useful synthetic intermediates for total synthesis. The reaction has been used in several total syntheses and several reviews have been published.
context_section_description: Though cyclizations following the general template above had been observed prior to Nazarov's involvement, it was his study of the rearrangements of allyl vinyl ketones that marked the first major examination of this process. Nazarov correctly reasoned that the allylic olefin isomerized in situ to form a divinyl ketone before ring closure to the cyclopentenone product. The reaction shown below involves an alkyne oxymercuration reaction to generate the requisite ketone.
  Research involving the reaction was relatively quiet in subsequent years, until in the mid-1980s when several syntheses employing the Nazarov cyclization were published. Shown below are key steps in the syntheses of Trichodiene and Nor-Sterepolide, the latter of which is thought to proceed via an unusual alkyne-allene isomerization that generates the divinyl ketone.
caption: Synthesis of Nor-Sterepolide using a classical Nazarov cyclization
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