Formal homo-Nazarov and other cyclization reactions of activated cyclopropanes

The Nazarov cyclization of divinyl ketones gives access to cyclopentenones. Replacing one of the vinyl groups by a cyclopropane leads to a formal homo‐Nazarov process for the synthesis of cyclohexenones. In contrast to the Nazarov reaction, the cyclization of vinyl‐cyclopropyl ketones is a stepwise process, often requiring harsh conditions. Herein, we describe two different approaches for further polarization of the three‐membered ring of vinyl‐cyclopropyl ketones to allow the formal homo‐Nazarov reaction under mild catalytic conditions. In the first approach, the introduction of an ester group α to the carbonyl on the cyclopropane gave a more than tenfold increase in reaction rate, allowing us to extend the scope of the reaction to non‐electron‐rich aryl donor substituents in the β position to the carbonyl on the cyclopropane. In this case, a proof of principle for asymmetric induction could be achieved using chiral Lewis acid catalysts. In the second approach, heteroatoms, especially nitrogen, were introduced β to the carbonyl on the cyclopropane. In this case, the reaction was especially successful when the vinyl group was replaced by an indole heterocycle. With a free indole, the formal homo‐Nazarov cyclization on the C3 position of indole was observed using a copper catalyst. In contrast, a new cyclization reaction on the N1 position was observed with Brønsted acid catalysts. Both reactions were applied to the synthesis of natural alkaloids. Preliminary investigations on the rationalization of the observed regioselectivity are also reported.     

Cyclopentene Annulations of Alkene Radical Cations with Vinyl Diazo Species Using Photocatalysis

A direct (3+2) cycloaddition between alkenes and vinyl diazo reagents using either Cr or Ru photocatalysis is described. The intermediacy of a radical cation species enables a nucleophilic interception by vinyl diazo compounds, a departure from their traditional electrophilic behavior. A variety of cyclopentenes are synthesized using this method, and experimental insights implicate a direct cycloaddition instead of a cyclopropanation/rearrangement process.     

Formation of halogenated cyclopent-2-enone derivatives by interrupted Nazarov cyclizations

Allenyl vinyl ketones were exposed to titanium and indium halides in order to carry out Nazarov cyclizations. Whereas TiI₄ and InX₃ (X = Cl, Br, and I) led to cyclopentenones in which a halogen was trapped highly regioselectively, the reactions mediated by TiBr₄ gave mixtures of brominated isomers. When the allenyl vinyl ketones were treated first with Br₂ and then with TiBr₄, doubly brominated cyclopentenones resulted, and treatment with I₂ followed by TFA gave cyclopentenones bearing both hydroxyl and iodo groups.     

Interrupting the Nazarov cyclization with indoles

A carbon-terminated interrupted Nazarov reaction is described. The trimethylsilyl enol ethers derived from propargyl vinyl ketones undergo selective proton transfer at the distal acetylenic carbon atom to provide allenyl vinyl ketones as transient intermediates. In the presence of indoles, a cascade of reactions is initiated that converts the initially formed pentadienyl cations to cyclopentenones bearing a quaternary alpha carbon atom.     

Synthesis of aminocyclopentitols from chromium carbene complex derived aminocyclobutanones

Functionalized cyclopentenones were synthesized by the diazomethane ring expansion of cyclobutanones, produced by the photochemical reaction of vinyl oxazolidinones with chromium carbene complexes.     

Photo-oxidation of metal carbynes

Photo-oxidation of the metal carbyne complexes (η-C⁵H₅)L₁L₂MCR (MMo, W; L₁, L₂CO, P(OMe)₃; R ≡ phenyl, cyclopropyl) generates radical that are extremely reactive. Depending on the reaction conditions, either the oxidized species exhibit the ligand exchange and atom abstraction processes typical of metal radicals, or the carbyne ligands undergo a series of highly unusual rearrangement to yield organic products. For the cyclopropyl carbynes (η⁵-C₅H₅)[P(OMe)₃](CO)MC(c-C₃H₅), photo-oxidation in the absence of added ligands results in the formation of cyclopentenone. When substituents are present on the cyclopropyl ring, single regioisomers or stereoisomers of the resulting cyclopentenones are produced.     

A new strategy for cyclopentenone synthesis

[reaction--see text] A new strategy for the synthesis of 2,3-disubstituted cyclopentenones emerges from two key reactions-the ruthenium-catalyzed three-component coupling of an equivalent of HBr, an alkyne, and a vinyl ketone and the Ni-Cr Barbier type reaction. As a result, these important structures are readily accessed from an alkyne and a vinyl ketone (which derive directly from carboxylic acids). Syntheses of tetrahydrodicranenone B and rosaprostol illustrate the new strategy.     

Isomerization-cyclization approach to the synthesis of 2-hydroxy-5-alkylidene-cyclopent-2-enones

[reaction: see text]. Propargyl vinyl ketones that are derived from the addition of 1-lithio-1-methoxymethoxy-2-ynes to morpholino enamides undergo isomerization followed by cyclization to alpha-methylene cyclopentenones upon exposure to silica gel.     

A Vinyl Cyclopropane Ring Expansion and Iridium-Catalyzed Hydrogen Borrowing Cascade

A vinyl cyclopropane rearrangement embedded in an iridium-catalyzed hydrogen borrowing reaction enabled the formation of substituted stereo-defined cyclopentanes from Ph* methyl ketone and cyclopropyl alcohols. Mechanistic studies provide evidence for the ring-expansion reaction being the result of a cascade based on oxidation of the cyclopropyl alcohols, followed by aldol condensation with the pentamethyl phenyl-substituted ketone to form an enone containing the vinyl cyclopropane. Subsequent single electron transfer (SET) to this system initiates a rearrangement, and the catalytic cycle is completed by reduction of the new enone. This process allows for the efficient formation of diversely substituted cyclopentanes as well as the construction of complex bicyclic carbon skeletons containing up to four contiguous stereocentres, all with high diastereoselectivity.     

Energetics of the biosynthesis of cyclopentenones from unsaturated fatty acids

Polyunsaturated fatty acids like linolenic acid or arachidonic acid upon enzymatic hydroxylation (lipoxygenases) can lead to corresponding hydroperoxides. Their dehydration gave rise to vinyl allene oxides, which cyclized into cyclopentenones, precursors of jasmonic acid or prostanoids.     

Oxidation-initiated Nazarov cyclization of vinyl alkoxyallenes

A mild method for the diastereoselective formation of C(4), C(5)-disubstituted cyclopentenones has been developed, involving formation of a pentadienyl cation via diastereoselective oxidation of a vinyl alkoxyallene. Conrotatory electrocyclization provides the cyclopentenone product. The broad scope, mild conditions, and uncommon substitution pattern accessible through this transformation make it a useful addition to the existing repertoire of cyclopentenone synthetic methods.     

Palladium-catalyzed coupling of vinyl tosylates with arylsulfinate salts

The first palladium-catalyzed coupling of vinyl tosylates with arylsulfinate salts is described. A variety of cyclic and acyclic vinyl tosylates were coupled with aryl sulfinate salts using 2.5 mol % Pd₂(dba)₃/5.0 mol % XantPhos to give vinyl aryl sulfone products in good yields. The coupling was extended to the preparation of a cyclopropyl vinyl sulfone.     

Visible Light Induced Brønsted Acid Assisted Pd-Catalyzed Alkyl Heck Reaction of Diazo Compounds and N-Tosylhydrazones

A mild visible light-induced palladium-catalyzed alkyl Heck reaction of diazo compounds and N-tosylhydrazones is reported. A broad range of vinyl arenes and heteroarenes with high functional group tolerance, as well as a range of different diazo compounds, can efficiently undergo this transformation. This method features Brønsted acid-assisted generation of hybrid palladium C(sp³)-centered radical intermediate, which allowed for new selective C?H functionalization protocol.     

A Vinyl Cyclopropane Ring Expansion and Iridium‐Catalyzed Hydrogen Borrowing Cascade

A vinyl cyclopropane rearrangement embedded in an iridium‐catalyzed hydrogen borrowing reaction enabled the formation of substituted stereo‐defined cyclopentanes from Ph* methyl ketone and cyclopropyl alcohols. Mechanistic studies provide evidence for the ring‐expansion reaction being the result of a cascade based on oxidation of the cyclopropyl alcohols, followed by aldol condensation with the pentamethyl phenyl‐substituted ketone to form an enone containing the vinyl cyclopropane. Subsequent single electron transfer (SET) to this system initiates a rearrangement, and the catalytic cycle is completed by reduction of the new enone. This process allows for the efficient formation of diversely substituted cyclopentanes as well as the construction of complex bicyclic carbon skeletons containing up to four contiguous stereocentres, all with high diastereoselectivity.     

Selective "one-pot" synthesis of functionalized cyclopentenones

Double addition (1,2-1,4) of vinyl magnesium bromide to squaric acid derivatives allows the preparation of polyoxygenated cyclopentenones (8) in a "one-pot" procedure. The reaction occurs through the intermediate formation of octatetraenes (6). Protonation of this latter intermediate at -78 °C with TFE occurs selectively at the vinyl CH(2) closer to the metallic centers. DFT studies of the cyclization step justify the observed diastereoselectivity.     

Synthesis of methyl-1-(tert-butoxycarbonylamino)-2-vinylcyclopropanecarboxylate via a Hofmann rearrangement utilizing trichloroisocyanuric acid as an oxidant

A trichloroisocyanuric acid (TCCA) mediated Hofmann rearrangement was utilized to synthesize methyl-1-(tert-butoxycarbonylamino)-2-vinylcyclopropanecarboxylate. A variety of functional groups are tolerated in this reaction including vinyl, cyclopropyl, pyridyl, aryl, benzyl, and nitro groups.     

Rapid Access to Oxabicyclo[2.2.2]octane Skeleton through Cu(I)‐Catalyzed Generation and Trapping of Vinyl‐o‐quinodimethanes (Vinyl‐o‐QDMs)†

A Cu(I)‐catalyzed three‐component reaction of terminal enynals/enynones, diazo compounds, and alkenes has been developed. With this method, a series of oxabicyclo[2.2.2]octanes were effectively synthesized in high yields under mild reaction conditions. This transformation is proposed to proceed through trapping of the cyclic vinyl‐o‐quinodimethanes (vinyl‐o‐QDMs) species, which were generated from terminal enynals/enynones and diazo compounds by alkenes. The obvious advantages of wide substrate scopes, mild reaction conditions, and high seteroselectivity and atom efficiency make this reaction highly appealing for construction of highly rigid [2.2.2]octane skeleton.     

Mechanistic and Preparative Aspects of Vinyl Cation Chemistry

Compelling evidence for the intermediacy of vinyl cations has accumulated in recent years. Vinyl cations can be generated by electrophilic additions to alkynes and allenes, and on participation of such functions in solvolysis reactions. Heterolysis of vinyl compounds likewise affords vinyl cations. Syntheses of substituted indenes, cyclobutanones, and cyclopropyl ketones illustrate preparative applications.     

Synthesis of spiropyrrolidine oxindoles through Rh(II)-catalyzed olefination/cyclization of diazooxindoles and vinyl azides

A simple and efficient process involving the Rh(II)-catalyzed [1+1+3] annulation of diazooxindoles and vinyl azides has been developed for the synthesis of spiropyrrolidine oxindoles with potential biological activity and significant synthetic applications. This process involves a novel rhodium-catalyzed olefination of diazo compounds, followed by annulation with vinyl azides. This method is compatible with a broad range of substrates and affords moderate to good yields under mild reaction conditions.     

The dechlorination of poly(vinyl chloride) by zinc and tributyl tin hydride.: Characterization of the product microstructures by carbon-13 NMR

Poly(vinyl chloride) has been reacted with zinc in refluxing dioxane for times in the range 18–113 h. The structure of the polymeric product has been examined by ¹H and ¹³C NMR spectroscopy. Contrary to earlier predictions, the reaction does not proceed only by 1,3-chlorine elimination to form cyclopropyl rings. Double bonds and methylene units are formed also, to give a polymer of considerable structural complexity. This complexity can be reduced by replacement of remaining chlorine with hydrogen after treatment with tributyl tin hydride. Analysis of the fully dechlorinated polymer shows that cyclopropyl rings are distributed randomly with a trans/cis ratio of about 2.6. A small number of cyclopentyl rings is observed also. A maximum of 9% of the original vinyl chloride units are dehydrochlorinated to give unconjugated vinylene units with a predominantly trans structure.