Nazarov Cyclization Research Articles

Studies toward the AB ring system of the tetrapetalone natural products

Synthetic efforts toward the rapid assembly of the AB ring system of the tetrapetalones is described. Key to this work was the use of [3+2] cycloaddition/oxidative extrusion methodology to furnish functionalized aryl enones. The Nazarov cyclization of these substrates was examined, and optimized to generate the AB ring carbon skeleton. Then, Pd-catalyzed cross-coupling were conducted, and conditions were identified that enabled installatiion of the requisite C14–N bond.

ChemInform Abstract: No Acid Required: 4π and 6π Electrocyclization Reactions of Dienyl Diketones for the Synthesis of Cyclopentenones and 2H‐Pyrans.

The 1,6-conjugate addition of nucleophiles to dienyl diketones produces either cyclopentenone or 2H-pyran products with high selectivity through either Nazarov (4π) or 6π electrocyclization, respectively. The outcome of the reaction is dependent upon the nature of the nucleophile used. Nucleophiles that are anionic or easily deprotonated exclusively produce cyclopentenones via Nazarov cyclization, whereas the neutral nucleophile DABCO promotes 6π cyclization to afford 2H-pyrans. Experimental evidence is presented for both retro-4π and -6π electrocyclization in these systems, lending support to the bifurcated mechanistic hypothesis proposed for these cyclizations.

Interception of Nazarov Reactions of Allenyl Vinyl Ketones with Dienes: (3+2)‐ versus (4+3)‐Cycloaddition and Subsequent Rearrangement

AbstractCapture of the cyclic oxyallyl cation intermediates from the BF3‐mediated Nazarov reactions of three allenyl vinyl ketones with various dienes was accomplished by (3+2)‐ and (4+3)‐cycloaddition. The relative amounts of these types of products were dependent on the substitution on the diene, and this could be linked to steric hindrance. Treatment of the (3+2)‐cycloaddition products with BF3·Et2O led mainly to decomposition but also to ring‐opened molecules and ring‐enlarged structures. The computed Gibbs energies of the (3+2)‐cycloaddition products, the products of the acid treatment and of some transition states leading to rearranged products were compared.

ChemInform Abstract: Iron‐Catalyzed Nazarov Reaction of Indole, Benzofuran, and Benzo[b]thiophene Derivatives.

AbstractA very simple protocol for the synthesis of cyclopentano‐fused indole (II), benzofuran and benzothiophene derivatives is developed using an economical Fe‐catalyzed Nazarov cyclization.

Nazarov cyclization of divinyl and arylvinyl epoxides: application in the synthesis of resveratrol-based natural products.

New variation in the Nazarov cyclization has been developed by preparing divinyl and arylvinyl epoxides as pentadienyl cation precursors for the first time. Highly substituted cyclopentadienes, hydrindienes, and indenes were synthesized to demonstrate the compatibility of this reaction with substrates bearing a variety of substitutions and having different types of epoxides. Application of this method in the synthesis of resveratrol-based natural products was also demonstrated.

Synthesis of new photochromic diarylethenes of cyclopentenone series by Nazarov reaction

An effective method is proposed for the synthesis of photochromic diarylethenes of cyclopentenone series with SnCl4-catalyzed 4π-electron cyclization of divinyl ketones by Nazarov reaction as the key step. It was shown that the introduction of an aryl group at position 4 of the cyclopentenone ring significantly improved the quantum yield of diarylethene photocyclization reaction.

Reactivity and stereoselectivity of 6π and nazarov electrocyclizations of bridged bicyclic trienes and divinyl ketones.

The 6π electrocyclizations and Nazarov cyclizations of a series of bridged bicyclic substrates were modeled with the M06-2X density functional and the def2-TZVPP basis set, and the factors responsible for the reactivities of these substrates and the stereoselectivities of their ring closures were identified. The ring closures of these bridged bicyclic trienes are up to a million-fold faster (ΔΔG(⧧) = 10 kcal mol(-1)) than that of 1,3,5-hexatriene, despite the absence of any activating functional groups. Three effects, preorganization, predistortion, and a CH π interaction, are responsible for this sizable difference in reactivity. Stereoselectivity is partially controlled by torsional effects, but for highly exo selective electrocyclizations, it is reinforced by a second effect (either a CH π interaction or a steric clash). The absence of this second effect in the ring closures of several divinyl ketones explains the reduced selectivity of these ring closures. In one case, a divinyl ketone (ketone 6) undergoes Nazarov cyclization to yield the endo product preferentially. For this example, through-space interaction of a nonconjugated alkene with the divinyl ketone π system in the endo transition state and a steric effect override the intrinsic exo selectivity.

ChemInform Abstract: The Nazarov Cyclization: A Valuable Method to Synthesize Fully Substituted Carbon Stereocenters

AbstractReview: [three general approaches to the formation of fully substituted quaternary carbon stereocenters by means of the Nazarov cyclization; 60 refs.

ChemInform Abstract: Highly Diastereoselective Synthesis of Cyclopentenones via a One‐Pot Gold Catalysis, Nazarov Cyclization and Alkylation Cascade.

AbstractPropargylic carboxylates are converted to cyclopentenones by alkyl halogenides or nitrostyrene in a gold‐catalyzed three‐step one‐pot synthesis.

ChemInform Abstract: The First Calcium‐Catalyzed Nazarov Cyclization.

AbstractThe first calcium‐catalyzed Nazarov cyclization is described.

ChemInform Abstract: Ready Access to Alkylidenecyclopentenones by Nazarov Cyclization/β‐Elimination of 2‐Hydroxyalkyl‐1,4‐dien‐3‐ones.

Cross-conjugated dienones bearing α-hydroxyalkyl substituents readily undergo Nazarov cyclization followed by deprotonation of the resulting cyclopentenyl cation, and β-elimination of the exocyclic hydroxy group to form alkylidenecyclopentenones in moderate yield. The deprotonation step occurs with complete regioselectivity opposite to the hydroxyalkyl substituent, with preferential introduction of an endocyclic olefin. The transformation is tolerant of a variety of substituents and occurs under relatively mild conditions.

Enantioselective Nazarov cyclization catalyzed by a cinchona alkaloid derivative

Nucleophilic catalysts for a 1,6 addition/Nazarov cyclization/elimination sequence were evaluated for their ability to induce enantioselectivity in the electrocyclization step. Of the tertiary amines examined, it was found that a cinchona alkaloid derivative was able to generate substituted 5-hydroxy γ-methylene cyclopentenones with excellent enantioselectivity. The study results suggest that successful cyclization depends upon the ability of the dienyl diketone substrate to readily adopt an s-cis conformation.

Torquoselectivity in the Nazarov reactions of allenyl vinyl ketones.

Nazarov reactions mediated by BF3-etherate of a series of carbon-substituted allenyl vinyl ketones provided intermediates in which substituents on the termini of the allenes had rotated away from the vinyl moieties, and these intermediates were trapped by (4 + 3)-cyclizations. A computational examination of the torquoselectivity of these Nazarov reactions confirmed a kinetic preference for the observed isomers and pointed to steric interactions and the degree of allene deformation as significant factors in determining the torquoselectivity. The study also suggested that the high proportion of one geometrical isomer in the Nazarov products might also be due to some preferential trapping of the major Nazarov intermediate.

ChemInform Abstract: The Photo‐Nazarov Reaction: Scope and Application.

AbstractIn contrast to the traditional Broensted‐ or Lewis acid‐promoted Nazarov cyclization reactions the photo‐Nazarov cyclization of vinyl aryl ketones proceeds under mild, neutral or basic conditions.

ChemInform Abstract: Synthesis of 5‐epi‐Taiwaniaquinone G.

A concise synthetic approach to the unnatural 5-epi-taiwaniaquinone G has been developed via a Lewis acid catalyzed tandem acylation–Nazarov cyclization reaction to construct the tricyclic skeleton, followed by installation of the isopropyl group through a strategy involving coumarin formation and its subsequent hydrolysis.

Nazarov cyclization of dienylaziridines: synthesis of cyclopentadienyl/hydrinedienyl/indenyl glycines.

Cyclopentadienyl, hydrinedienyl, and indenyl glycines were synthesized using dienylaziridines as Nazarov cyclization precursors for the first time. Several substrates were synthesized to demonstrate the compatibility of this reaction. Asymmetric synthesis of these amino acids was also developed to show the additional scope of this method.

Efficient catalytic enantioselective Nazarov cyclizations of divinyl ketoesters

An efficient catalytic enantioselective Nazarov cyclization of divinyl ketoesters is developed using a BOX/Cu(ii) catalyst, affording various optically active cyclopent-2-enone esters.

Cellulose sulfonic acid as a green, efficient, and reusable catalyst for Nazarov cyclization of unactivated dienones and pyrazoline synthesis

A high yielding and eco-friendly procedure for the preparation of cyclopentenoid and pyrazoline derivatives via cellulose sulfonic acid-mediated electrocyclization processes.

Studies Towards a Concise Enantioselective Synthesis of Roseophilins

An oxazolidone auxiliary-controlled asymmetric Nazarov reaction has been applied to the synthesis of the cyclopentyl-fused pyrrole core of roseophilins. Additionally, a concise synthetic route to the pyrrole-furan biaryl fragment required in the synthesis of the recently isolated dechlororoseophilin is described. It is anticipated that these two syntheses can be combined in future efforts to provide efficient, convergent access to (+)-dechlororoseophilin.

Experimental and computational study of the catalytic asymmetric 4π-electrocyclization of N-heterocycles.

The first asymmetric metal-catalyzed Nazarov cyclization of N-heterocycles has been developed. The use of a chiral catalyst allows the enantioselective electrocyclization of N-heterocycles under mild conditions and the corresponding products are obtained in good yields with excellent enantio- and diastereoselectivity. The reaction mechanism and the absolute configuration of the obtained products are explained by means of computational studies.