The Nazarov Cyclization of Cross-Conjugated Ketones

Electrocyclization reactions are powerful synthetic tools to prepare compounds of great molecular diversity. These reactions allow for the formation of many substituted cyclic and polycychc compounds important in medicine, materials science, cosmetics, and so on. The well-established mechanisms and predictable outcomes of electrocyclization reactions permit the elaboration of logical blueprints for the synthesis of important molecules. Among these, the Nazarov cyclization is a salient member of the family. Reported first in 1941 by Ivan Nikolaevich Nazarov [1], this reaction has been studied extensively and many variations and applications have been developed over the years. In this chapter, we will present selected examples highlighting the versatility and synthetic power of this transformation [2]. In its simplest form, the Nazarov employs a divinyl ketone as the starting material, a cross-conjugated compound which can be regarded as a 3 -oxa-[3]dendralene. 

The high stereocontrol of the reaction is attributed to the conservation of orbital symmetry. According to frontier molecular orbital (FMO) theory, the 

Cross Conjugation Dendralene, Radialene and Fulvene Chemistry, First Edition. 

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A synthesis of cross-conjugated 2-cyclopenten-l-ones from dialkenyl ketones is readily induced by TMSOTf (eq 73). A strong fluorine-directing effect has been observed for such Nazarov-type cycUzation, as mixtures of products have been observed for nonfluorinated dialkenyl ketones. The addition of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a cosolvent dramatically accelerates the cyclization. Other acids such as BF3-OEt2, FeCls, polyphosphoric acid, or TiOH are less effective while neither TMSI nor TMSOMe promote this cyclization at all in CH2CI2. 3-Ethoxycarbonyltetrahydro-)/-pyrones also undergo such Nazarov-type cyclization. ... 

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