Nazarov Cyclization Research Articles

Gold-catalyzed dehydrative Friedel–Crafts reaction and Nazarov cyclization sequence: an efficient synthesis of 1,3-diarylindenes from propargylic alcohols

An efficient synthesis of 1,3-diarylindenes has been achieved from propargylic alcohols containing aromatic rings via gold-catalyzed dehydrative Friedel–Crafts reaction followed by gold-catalyzed Nazarov cyclization. The reaction proceeds via allene intermediates.

Direct Synthesis of Perylene‐Fused Cyclic Ketones from Perylene and 2‐Alkenoic Acids

An efficient, one‐pot methodology of direct synthesis of perylene‐fused cyclic ketones from perylene and 2‐alkenoic acids under acidic catalytic conditions has been developed. The reaction of perylene with 2,3‐disubstituted 2‐alkenoic acid leads, via Friedel–Crafts acylation followed by Nazarov cyclization, to the formation of disubstituted 5,6‐dihydro‐4H‐cyclopenta[b]perylen‐4‐ones in high yield (up to 97 %) and high diastereoselectivity, whereas the reaction with acrylic acid leads, via alkylation followed by intramolecular Friedel–Crafts acylation, to 2,3‐dihydro‐1H‐benzo[cd]perylen‐1‐one.

ChemInform Abstract: Recent Progress on Nazarov Cyclizations: The Use of Iron Salts as Catalysts in Ionic Liquid Solvent Systems

AbstractReview: [60 refs.

ChemInform Abstract: Synthesis of Chiral Cyclopentenones

AbstractReview: 656 refs.

ChemInform Abstract: Nazarov Cyclization of Divinyl Ketones Bearing an Ester Group at the β‐Position: A Remarkable Effect of α‐Substitution and Alkene Geometry on Regioselectivity.

The Nazarov cyclization of divinyl ketones with an ester at the β-position was examined with particular reference to where the cyclic double bond forms. We observed unprecedented regioselectivity, dictated by the subtle substitution patterns at the α-position and alkene geometry of α,β and mostly, this selectivity is regardless of substitutions at α′- and β′-positions. The major implications of these observations are an aromatic group at the α-position with E-olefin geometry provides a cyclopentenone in which the double bond is not in conjugation with an ester, whereas Z-olefin provides a cyclopentenone in which the double bond is in conjugation with an ester; and divinyl ketones bearing an ester group at the β-position and an alkyl group at the α-position with E-olefin geometry provide a cyclopentenone in which the double bond is in conjugation with the ester.

Recent Progress on Nazarov Cyclizations: The Use of Iron Salts as Catalysts in Ionic Liquid Solvent Systems.

Nazarov cyclization is an important and versatile method for the synthesis of five-membered carbocycles, and extensive studies have been conducted to optimize the reaction. Among recent studies, several trends are recognized. One is the combination of different reactions with Nazarov cyclization in a one-pot reaction system which enables the preparation of unique cyclization products. The second is the use of a transition-metal catalyst, though Lewis or Brønsted acids have generally been used for the reaction. The third is the realization of the asymmetric Nazarov cyclization. The fourth is the base-catalyzed Nazarov cyclization. Furthermore, several useful protocols for realizing Nazarov cyclization have also been developed. The recent progress on Nazarov cyclizations is summarized in Section 2. Section 3 is our chronicle in this field. We focused on the use of iron as the catalyst in Nazarov cyclizations and ionic liquids as solvents: Nazarov cyclization of thiophene derivatives using FeCl3 as the catalyst was accomplished and we succeeded in demonstrating the first example of an iron-catalyzed asymmetric Nazarov reaction. We next established Nazarov cyclization of pyrrole or indole derivatives using Fe(ClO4 )3 ·Al2 O3 as the catalyst with high trans selectivities in excellent yields. Since the cyclized product was reacted with a vinyl ketone in the presence of the same iron salt, the system allowed realization of the sequential type of Nazarov/Michael reaction of pyrrole derivatives. Furthermore, we demonstrated the recyclable use of the iron catalyst and obtained the desired Nazarov/Michael reaction products in good yields for five repetitions of the reactions without any addition of the catalyst using an ionic liquid, [bmim][NTf2 ], as the solvent. We expect that the iron-catalyzed Nazarov cyclization, in particular, in an ionic liquid solvent might become a useful method to synthesize functional molecules that include cycloalkene moieties.

ChemInform Abstract: Nazarov Cyclization of 1,4‐Pentadien‐3‐ols: Preparation of Cyclopenta[b]indoles and Spiro[indene‐1,4′‐quinoline]s.

AbstractNew Lewis acid‐catalyzed cascade reactions based on Nazarov cyclization of pentadienols are developed.

ChemInform Abstract: Study on the Synthesis of the Cyclopenta[f]indole Core of Raputindole A.

The raputindoles from the rutaceous tree Raputia simulans share a cyclopenta[f]indole partial structure the synthesis of which is subject of this investigation. An efficient route to a series of 1,5-di(indol-6-yl)pentenones was developed via Mo/Au-catalyzed Meyer–Schuster rearrangement of tertiary propargylic alcohol precursors. However, none of the enones underwent the desired Nazarov cyclization to a cyclopenta[f]indole. More suitable were 6-hydroxyallylated indolines which gave good yields of cyclopenta[f]indolines after treatment with SnCl4, as soon as sterically demanding β-cyclocitral adducts were reacted. Most successful were Pt(II) and Au(I)-catalyzed cyclizations of N-TIPS-protected indolin-6-yl-substituted propargylacetates which provided the hydrogenated tricyclic cyclopenta[f]indole core system in high yield.

ChemInform Abstract: The First Intermolecular Interrupted Imino‐Nazarov Reaction: Expeditious Access to Carbocyclic Nucleoside Analogues.

The analogous imino-variant of the Nazarov reaction suffers from unfavorable energetics associated with the ring closure process, thereby limiting the utility of this class of reactions. In this report, the realization of the first intermolecular interrupted imino-Nazarov reaction utilizing silylated pyrimidine derivatives as nucleophilic trapping partners culminated in an expedient synthetic route to carbocyclic nucleoside analogues. The potential application of silylated nucleobases to intercept the oxyallyl cation in other variants of the Nazarov reaction provides vast opportunities to develop new strategies for the formation of carbocyclic nucleoside analogues.

Synthesis of Chiral Cyclopentenones.

The cyclopentenone unit is a very powerful synthon for the synthesis of a variety of bioactive target molecules. This is due to the broad diversity of chemical modifications available for the enone structural motif. In particular, chiral cyclopentenones are important precursors in the asymmetric synthesis of target chiral molecules. This Review provides an overview of reported methods for enantioselective and asymmetric syntheses of cyclopentenones, including chemical and enzymatic resolution, asymmetric synthesis via Pauson-Khand reaction, Nazarov cyclization and organocatalyzed reactions, asymmetric functionalization of the existing cyclopentenone unit, and functionalization of chiral building blocks.

ChemInform Abstract: Cellulose Sulfonic Acid as a Green, Efficient, and Reusable Catalyst for Nazarov Cyclization of Unactivated Dienones and Pyrazoline Synthesis.

AbstractCellulose sulfonic acid efficiently catalyzes both the cyclization of dienones and the cyclization of in situ generated α,β‐unsaturated hydrazones.

ChemInform Abstract: Hydroxylamine Catalyzed Nazarov Cyclizations of Divinyl Ketones.

Abstract The first examples of iminium catalyzed Nazarov cyclizations of divinyl ketones are presented. Experiments describing hydroxylamine catalysis of the cyclization of eight α-alkoxy divinyl ketones (60–79% yield) and one unactivated divinyl ketone (38% yield) are reported. Phenyl substitution at the β-position of the divinyl ketone inhibits cyclization, whereas β-alkyl substituted α-alkoxy divinyl ketones readily cyclize.

Study on the synthesis of the cyclopenta[f]indole core of raputindole A.

The raputindoles from the rutaceous tree Raputia simulans share a cyclopenta[f]indole partial structure the synthesis of which is subject of this investigation. An efficient route to a series of 1,5-di(indol-6-yl)pentenones was developed via Mo/Au-catalyzed Meyer–Schuster rearrangement of tertiary propargylic alcohol precursors. However, none of the enones underwent the desired Nazarov cyclization to a cyclopenta[f]indole. More suitable were 6-hydroxyallylated indolines which gave good yields of cyclopenta[f]indolines after treatment with SnCl4, as soon as sterically demanding β-cyclocitral adducts were reacted. Most successful were Pt(II) and Au(I)-catalyzed cyclizations of N-TIPS-protected indolin-6-yl-substituted propargylacetates which provided the hydrogenated tricyclic cyclopenta[f]indole core system in high yield.

ChemInform Abstract: Nazarov Cyclization of Dienylaziridines: Synthesis of Cyclopentadienyl/Hydrinedienyl/Indenyl Glycines.

AbstractDienylaziridines, prepared in situ from the corresponding vinyl imines, undergo Nazarov cyclization reactions providing access to the title glycine derivatives in good yields.

Nazarov cyclization of 1,4-pentadien-3-ols: preparation of cyclopenta[b]indoles and spiro[indene-1,4'-quinoline]s.

The first Lewis acid-catalyzed intramolecular interrupted Nazarov cyclization of 1,4-pentadien-3-ols is described. Using FeBr3 as the catalyst, a series of new substituted cyclopenta[b]indoles was prepared-through a sequence of Nazarov cyclization, nucleophilic amination, and isomerization-with good yields and high diastereo- and regioselectivities. A similar catalytic process was also developed for the synthesis of structurally interesting spiro[indene-1,4'-quinoline]s.

Approach to Phenanthroindolizidine Alkaloids Using Organic Azides with 1-Aryl Allylic Alcohols: Unexpected Tandem Reactions to Indenyl Aziridines via Nazarov Cyclization

Approach to Phenanthroindolizidine Alkaloids Using Organic Azides with 1-Aryl Allylic Alcohols: Unexpected Tandem Reactions to Indenyl Aziridines via Nazarov Cyclization

A Cr(salen)-based metal-organic framework as a versatile catalyst for efficient asymmetric transformations.

A porous Cr(salen)-MOF can serve as an efficient and effective heterogeneous catalyst for a series of important asymmetric transformations including the Nazarov cyclization, aminolysis reaction, and Diels-Alder and hetero Diels-Alder reactions, resulting in comparable or superior diastereo- or enantioselectivity with respect to the corresponding homogeneous systems.

Nazarov cyclization of divinyl ketones bearing an ester group at the β-position: a remarkable effect of α-substitution and alkene geometry on regioselectivity.

The Nazarov cyclization of divinyl ketones with an ester at the β-position was examined with particular reference to where the cyclic double bond forms. We observed unprecedented regioselectivity, dictated by the subtle substitution patterns at the α-position and alkene geometry of α,β and mostly, this selectivity is regardless of substitutions at α'- and β'-positions. The major implications of these observations are an aromatic group at the α-position with E-olefin geometry provides a cyclopentenone in which the double bond is not in conjugation with an ester, whereas Z-olefin provides a cyclopentenone in which the double bond is in conjugation with an ester; and divinyl ketones bearing an ester group at the β-position and an alkyl group at the α-position with E-olefin geometry provide a cyclopentenone in which the double bond is in conjugation with the ester.

MeOTf-catalyzed annulation of aldehydes and arylalkynes leading to 2,3-disubstituted indanones

MeOTf-catalyzed arylalkyne–aldehyde metathesis and Nazarov cyclization represent a sustainable and atom-economical approach for the construction of indanones with high stereoselectivity.

Computational Examination of (4 + 3) versus (3 + 2) Cycloaddition in the Interception of Nazarov Reactions of Allenyl Vinyl Ketones by Dienes.

A computational examination of the tandem Nazarov/cycloaddition process involving an allenyl vinyl ketone with a diene has been carried out using the ωB97X-D/6-311++G(d,p)//ωB97X-D/6-31+G(d,p) method with solvation modeled by SMD-PCM. The barrier for the initial Lewis acid mediated Nazarov reaction, which provided the intermediate cyclic oxylallyl cation, was higher than that for any subsequent cycloaddition. The barrier for the first step of a subsequent stepwise reaction did not vary much with the diene, and the lowest barrier was with the diene in its s-trans conformation. Stepwise formation of a (4 + 3) cycloaddition product was not energetically feasible, but (3 + 2) cycloaddition products could have been produced through low energy pathways. The barrier for a concerted (4 + 3) cycloaddition did depend upon the diene, which was always in an s-cis geometry. The barriers for the compact and the extended geometries for the transition states of (4 + 3) cycloadditions were not much different.