Carbocyclic Structures Research Articles

Directed C−H Allylation of Aromatic Carboxamides with Allyl Aryl Ethers under Cp*Co(III)‐Catalysis

AbstractThe Cp*Co(III) C−H allylation of (hetero)arenes with allyl aryl ethers has been developed using an amide as directing group (24 examples). DFT calculations have shed light on the mechanistic course and reactivity pattern, showing that strong electron releasing groups favour the reaction by reducing the activation barrier of the rate‐determining C−H activation step. However, the steric strain can increase the energy of the migratory insertion step to the point of completely preventing the reaction, as in the case of the 3,5‐dimethylbenzamide. The obtained allylated compounds have been transformed into a variety of interesting heterocyclic and carbocyclic structures, such as isoquinolones and isochromanones.

Asymmetric Synthesis of α-Spiro-γ-lactones and α-Substituted γ-Lactones via Chiral Bifunctional Sulfide-Catalyzed Bromolactonizations.

An efficient enantioselective synthesis of γ-chiral α-spiro-γ-lactones, which are important building blocks for pharmaceuticals, was achieved via BINOL-derived chiral bifunctional sulfide-catalyzed bromolactonizations of α-allyl carboxylic acids containing either hetero- or carbocyclic structures. Transformations of the resultant α-spiro-type bromolactonization product were examined to obtain optically active γ-functionalized α-spiro-γ-lactones. The utility of this catalytic system was also demonstrated in the asymmetric synthesis of α,α-diaryl- and dialkyl-substituted γ-lactones.

Rapid Access to 2-Substituted Bicyclo[1.1.1]pentanes.

The replacement of aryl rings with saturated carbocyclic structures has garnered significant interest in drug discovery due to the potential for improved pharmacokinetic properties upon substitution. In particular, 1,3-difunctionalized bicyclo[1.1.1]pentanes (BCPs) have been widely adopted as bioisosteres for parasubstituted arene rings, appearing in a number of lead pharmaceutical candidates. However, despite the pharmaceutical value of 2-substituted BCPs as replacements for ortho- or meta-substituted arene rings, general and rapid syntheses of these scaffolds remain elusive. Current approaches to 2-substituted BCPs rely on installation of the bridge substituent prior to BCP core construction, leading to lengthy step counts and often nonmodular sequences. While challenging, direct functionalization of the strong bridge BCP C-H bonds would offer a more streamlined pathway to diverse 2-substituted BCPs. Here, we report a generalizable synthetic linchpin strategy for bridge functionalization via radical C-H abstraction of the BCP core. Through mild generation of a strong hydrogen atom abstractor, we rapidly synthesize novel 2-substituted BCP synthetic linchpins in one pot. These synthetic linchpins then serve as common precursors to complex 2-substituted BCPs, allowing one-step access to a number of previously inaccessible electrophile and nucleophile fragments at the 2-position via two new metallaphotoredox protocols. Altogether, this platform enables the expedient synthesis of four pharmaceutical analogues, all of which show similar or improved properties compared to their aryl-containing equivalents, demonstrating the potential of these 2-substituted BCPs in drug development.

On‐Surface Synthesis of [3]Radialenes via [1+1+1] Cycloaddition

[3]Radialenes are the smallest carbocyclic structures with unusual topologies and cross-conjugated π-electronic structures. Here, we report a novel [1+1+1] cycloaddition reaction for the synthesis of aza[3]radialenes on the Ag(111) surface, where the steric hindrance of the chlorine substituents guides the selective and orientational assembling of the isocyanide precursors. By combining scanning tunneling microscopy, non-contact atomic force microscopy, and time-of-flight secondary ion mass spectrometry, we determined the atomic structure of the produced aza[3]radialenes. Furthermore, two reaction pathways including synergistic and stepwise are proposed based on density functional theory calculations, which reveal the role of the chlorine substituents in the activation of the isocyano groups via electrostatic interaction.

On-Surface Synthesis of [3]Radialenes via [1+1+1] Cycloaddition.

[3]Radialenes are the smallest carbocyclic structures with unusual topologies and cross-conjugated π-electronic structures. Here, we report a novel [1+1+1] cycloaddition reaction for the synthesis of aza[3]radialenes on the Ag(111) surface, where the steric hindrance of the chlorine substituents guides the selective and orientational assembling of the isocyanide precursors. By combining scanning tunneling microscopy, non-contact atomic force microscopy, and time-of-flight secondary ion mass spectrometry, we determined the atomic structure of the produced aza[3]radialenes. Furthermore, two reaction pathways including synergistic and stepwise are proposed based on density functional theory calculations, which reveal the role of the chlorine substituents in the activation of the isocyano groups via electrostatic interaction.

Reactions of linear conjugated dienone structures with arenes under superelectrophilic activation conditions. An experimental and theoretical study of intermediate multicentered electrophilic species

Reactions of conjugated dienones with arenes under superelectrophilic activation conditions result in the formation of conjugated enones, indanes, and carbocyclic structures.

Biosynthesis of cyclitols.

Review covering up to 2021Cyclitols derived from carbohydrates are naturally stable hydrophilic substances under ordinary physiological conditions, increasing the water solubility of whole molecules in cells. The stability of cyclitols is derived from their carbocyclic structures bearing no acetal groups, in contrast to sugar molecules. Therefore, carbocycle-forming reactions are critical for the biosynthesis of cyclitols. Herein, we review naturally occurring cyclitols that have been identified to date and categorize them according to the type of carbocycle-forming enzymatic reaction. Furthermore, the cyclitol-forming enzymatic reaction mechanisms and modification pathways of the initially generated cyclitols are reviewed.

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds.

The synthesis of complex cyclic compounds is extremely challenging for organic chemists. Many transition-metal-salt-mediated cyclizations are reported in literature. Hg(II) salts have been successfully employed in cyclizations to form complex heterocyclic and carbocyclic structures that are impossible to synthesize with other transition metal salts. In this review, we have summarized cyclization reactions that are performed with Hg(II) salts. These salts are also successfully applied in stoichiometric or catalytic amounts to form complex cyclic structures and natural products.

Tailored cobalt-salen complexes enable electrocatalytic intramolecular allylic C\u2013H functionalizations

Oxidative allylic C–H functionalization is a powerful tool to streamline organic synthesis as it minimizes the need for functional group activation and generates alkenyl-substituted products amenable to further chemical modifications. The intramolecular variants can be used to construct functionalized ring structures but remain limited in scope and by their frequent requirement for noble metal catalysts and stoichiometric chemical oxidants. Here we report an oxidant-free, electrocatalytic approach to achieve intramolecular oxidative allylic C–H amination and alkylation by employing tailored cobalt-salen complexes as catalysts. These reactions proceed through a radical mechanism and display broad tolerance of functional groups and alkene substitution patterns, allowing efficient coupling of di-, tri- and even tetrasubstituted alkenes with N- and C-nucleophiles to furnish high-value heterocyclic and carbocyclic structures.

Perrhenate Esters as Intermediates in Molecular Complexity-Increasing Reactions

AbstractAllylic alcohols form perrhenate esters upon reaction with Re2O7 or HOReO3. These species undergo nonstereospecific and nonregiospecific alcohol-transposition reactions through cationic intermediates. Sequencing these nonselective processes with reversible trapping by electrophiles results in cyclization reactions where regio- and stereocontrol are dictated by thermodynamics. The cationic intermediates can also be utilized as electrophiles in intra- or intermolecular dehydrative reactions with nucleophiles. These processes serve as the basis for applications in catalytic syntheses of a wide range of heterocyclic and carbocyclic structures that often show considerable increases in molecular complexity. This Account describes a sequence of events that started from a need to solve a problem for the completion of a natural product synthesis and evolved into a central element in the design of numerous new transformations that proceed under mild conditions from readily accessible substrates.1 Introduction2 Exploratory Studies3 Application to Spiroketal Synthesis4 Reactions with Epoxides as Trapping Agents5 Development of Dehydrative Cyclizations6 Bimolecular Reactions7 Spirocyclic Ether Formation8 Conclusions

TfOH-Promoted Reactions of TMS-Ethers of CF3-Pentenynoles with Arenes. Synthesis of CF3-Substituted Pentenynes, Indenes, and Other Carbocyclic Structures.

Trimethylsilyl ethers of 1,5-diaryl-3-(trifluoromethyl)-pent-1-en-4-yn-3-oles [Ar-C≡C-C(CF3)(OSiMe3)-CH═CH-Ar'] in the superacid TfOH give rise to reactive conjugated CF3-allylic-propargylic cations [Ar-C≡C-C+(CF3)-CH═CH-Ar']. These species react with arenes in the presence of 1.5 equiv of TfOH forming regio- and stereoselectively E-1,1,5-triaryl-3-(trifluoromethyl)-pent-2-en-4-ynes [Ar-C≡C-C(CF3)═CH-CHAr'(Ar″)] in good yields. In the excess of TfOH, these CF3-pentenynes are further intramolecularly cyclized into CF3-bicyclic dihydroanthracene derivatives ("helicopter"-like molecules). The CF3-pentenynes may also react with arenes, as external nucleophiles, leading to CF3-indenes. These two main reaction pathways depend on internal nucleophilicity of aryl substituents in CF3-pentenynes and external nucleophilicity of aromatic molecules. Plausible cationic reaction mechanisms have been discussed. CF3-bicyclic dihydroanthracene derivatives have been studied regarding their cytotoxicity and virus-inhibiting activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cell line.

Thermal behavior of chitosan as a carbon material precursor under IR radiation

An effective accelerated synthesis procedure of a carbon material based on chitosan via infrared pyrolysis was developed. Infrared radiation heating allows to shorten preparation time significantly. It takes only 2 min of the residence time at 800 °C for complete carbonization of the polymer. The chemical transformations in chitosan during infrared pyrolysis depended on temperature were studied. The formation of C=C–C=N and C=C–C=C conjugated bonds at a low-temperature stage of the carbonization process was demonstrated. It was revealed that the main product of the chitosan pyrolysis at 600-800 °C represents a graphite-like carbon material in the form of carbocyclic structures.

Gold(I)‐Catalysis for the Synthesis of Terpenoids: From Intramolecular Cascades to Intermolecular Cycloadditions

AbstractGold(I)‐catalyzed cycloisomerizations of 1,n‐enynes proceed through electrophilic intermediates that can be trapped intra‐ or intermolecularly by a variety of hetero‐ and carbon nucleophiles to form complex skeletons in a single step. This review covers the efforts of our group towards the development of new reactions that have been successfully applied in the total synthesis of several natural terpenoids and related carbocyclic structures, as well as for the ready access to challenging linear acenes.

5]Radialene.

The [n]radialenes are a unique family of fundamental [n]-membered carbocyclic structures with radiating alkenes, which have attracted significant synthetic and theoretical attention. Whereas [3]-, [4]-, and [6]radialenes have been prepared and studied, all efforts to synthesize the five-membered ring compound have thus far met with failure. Here we describe the first synthesis of the fundamental hydrocarbon [5]radialene, C10H10. Our approach was a departure from previous radialene syntheses in that it utilized a low-temperature decomplexation of a stable organometallic compound, rather than high-temperature elimination or rearrangement. Our strategy was guided by analysis of previous radialene syntheses, which indicated rapid decomposition in oxygen, and ab initio calculations, which revealed an extraordinary susceptibility of [5]radialene to undergo Diels-Alder dimerization/polymerization. The origin of this susceptibility was traced to a small distortion energy associated with the formation of the transition structure geometry from the relaxed reactant monomers and to a narrow HOMO-LUMO gap.

ChemInform Abstract: Harnessing the Versatile Reactivity of Propargyl Alcohols and Their Derivatives for Sustainable Complex Molecule Synthesis

AbstractReview: [72 refs.

ChemInform Abstract: Organocatalytic Asymmetric Strategies to Carbocyclic Structures by γ‐Alkylation‐Annulation Sequences.

AbstractVinyl phosphonates (II) and (VIII) as well as nitro olefins (XI) and (XIII) react with annulated cyclic enals (I), (IV), (VI) and (X) to carbocyclic derivatives (III), (V), (VII), (IX), (XII), and (XIV) in a highly regio‐ and enantioselective manner using proline‐based derivatives as chiral catalysts.

Organocatalytic asymmetric strategies to carbocyclic structures by γ-alkylation-annulation sequences

Attractive carbocyclic structures are accessed via a highly regio- and enantioselective aminocatalytic γ-addition of cyclic enals to vinyl phosphonates followed by a one-pot intramolecular Horner-Wadsworth-Emmons reaction. It is also demonstrated that nitro olefins can act as electrophiles in a similar reaction concept, providing carbocycles in equally high stereoselectivity.

Ruthenium‐Catalyzed Cascade CH Functionalization of Phenylacetophenones

AbstractThree orthogonal cascade CH functionalization processes are described, based on ruthenium‐catalyzed CH alkenylation. 1‐Indanones, indeno indenes, and indeno furanones were accessed through cascade pathways by using arylacetophenones as substrates under conditions of catalytic [{Ru(p‐cymene)Cl2}2] and stoichiometric Cu(OAc)2. Each transformation uses CH functionalization methods to form CC bonds sequentially, with the indeno furanone synthesis featuring a CO bond formation as the terminating step. This work demonstrates the power of ruthenium‐catalyzed alkenylation as a platform reaction to develop more complex transformations, with multiple CH functionalization steps taking place in a single operation to access novel carbocyclic structures.

Ruthenium-catalyzed cascade C-H functionalization of phenylacetophenones.

Three orthogonal cascade C—H functionalization processes are described, based on ruthenium-catalyzed C—H alkenylation. 1-Indanones, indeno indenes, and indeno furanones were accessed through cascade pathways by using arylacetophenones as substrates under conditions of catalytic [{Ru(p-cymene)Cl2}2] and stoichiometric Cu(OAc)2. Each transformation uses C—H functionalization methods to form C—C bonds sequentially, with the indeno furanone synthesis featuring a C—O bond formation as the terminating step. This work demonstrates the power of ruthenium-catalyzed alkenylation as a platform reaction to develop more complex transformations, with multiple C—H functionalization steps taking place in a single operation to access novel carbocyclic structures.

Gold‐Catalyzed Functionalization of Unactivated C(sp3)H Bonds by Hydride Transfer Facilitated by Alkynylspirocyclopropanes

A Golden Gate: Alkynylspirocyclopropanes served as a template for the development of gold-catalyzed hydride transfer from unactivated C(sp3)H bonds to electronically neutral alkynes. A variety of interesting carbocyclic structures can be accessed selectively with the appropriate choice of the reaction conditions. Mechanistic studies support a sequential gold-catalyzed cleavage of CH and CC bonds.