Nucleophiles Nazarov cyclization

As described above, our synthetic strategy involves the convergent construction of the central cyclopentanone ring with a carbonylative cross-coupling reaction and a photo-Nazarov cyclization reaction (Chart 2.2). The electrophilic coupling component 51 was synthesized by an intramolecular Diels-Alder reaction [34] and the nucleophilic coupling component 52 by a vinyiogous Mukaiyama aldol reaction [35]. 

The abnormal Nazarov cyclization reported by Hiyama leads to transposed cyclopentenones by incorporating carboxylic acids as nucleophiles in the reaction medium. Both acyclic and monocyclic divinyl ketones can be employed, as shown in Scheme 15. Dioxolane acetals have also been used successfully in place of the carbonyl group. 

Electrocyclic reactions are not limited to neutral polyenes. The cyclization of a pentadienyl cation to a cyclopentenyl cation offers a useful entry to five-membered carbocycUc compounds. One such reaction is the Nazarov cyclization of divinyl ketones. Protonation or Lewis acid complexation of the oxygen atom of the carbonyl group of a divinyl ketone generates a pentadienyl cation. This cation undergoes electrocyclization to give an allyl cation within a cyclopentane ring. The allyl cation can lose a proton or be trapped, for example by a nucleophile. Proton loss occurs to give the thermodynamically more stable alkene and subsequent keto-enol tautomerism leads to the typical Nazarov product, a cyclopentenone (3.220). 

The Nazarov cyclization is a four-electron cyclization and occurs thermally by a conrotatory process. The stereochemical outcome across the new carbon-carbon bond is often obscured by the loss of a proton at one of these centres during the cyclopentenone formation. If, however, the proton loss occurs exo to the five-membered ring or if the aUyl cation is quenched by a nucleophile, then the stereochemistry can be observed. For example, trapping the allyl cation by reduction with... 

Q -electron-donating effect of fluorine to control the regiochemistry (Scheme 3). Analogous to silicon, tin is also used to direct the Nazarov cyclization. " The interrupted Nazarov reaction has been developed by West et al. to extend the reaction of the cationic endocyclic intermediate with carbon nucleophiles. Furthermore, this reaction has been extended to imino-Nazarov cyclization of vinyl allenyl imine. ... 

Intermolecular capture of cationic intermediates resulting from Nazarov cyclizations has been demonstrated with added nucleophiles. For example, allyl silanes can be used to either generate a-allyl ketones or [3 + 2] cyclization products. ... 

Nazarov-type Reactions. It has been shown that the highly Lewis acidic Sc(OTf)3 and Yb(OTf)3 can catalyze the Nazarov cyclization. Recently, Dy(OTf)3 has been err5>loyed to catalyze the rearrangement of furfural and furylcarbinol reagents. These rearrangements are proposed to terminate in Nazarov-type 47T electrocyclizations. A Dy(OTf)3-catalyzed formation of trans-4,5-diamino-2-cyclopenten- 1-ones fromfurfural and nitrogen nucleophiles has been disclosed (eq 5). ... 

Whereas the photochemical Nazarov cyclizations that are terminated through intermolecular nucleophilic attack typically give only modest yields of product, those that are terminated intramolecularly are highly efficient. West and co-workers have demonstrated trapping by a pendant hydroxyl group as indicated in Scheme 19.37. When methanol was used as the photolysis solvent instead of poorly nucleophilic trifluoroethanol, the yield of 141 dropped to 60%. A diastereomeric mixture of the methanol adducts to the epoxy zwitterion was also isolated in 14— 16% yield. Intramolecular trapping by electron-rich aryls and alkenes has also been demonstrated. 

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