Ring Expansion Reaction Research Articles

Direct synthesis of highly functionalized furans from donor-acceptor cyclopropanes via DBU-mediated ring expansion reactions.

A DBU-mediated, unprecedented formal ring expansion reaction of 2-acyl-3-arylcyclopropane-1,1-dicarbonitriles for the synthesis of multisubstituted furan derivatives is reported. This transformation represents the regioselective ring-opening reaction of cyclopropane-1,1-dicarbonitriles and annulation using an intramolecular addition cascade reaction protocol for the synthesis of fully substituted furans includes use of readily available starting materials, mild reaction conditions, and it is transition-metal catalyst free, has good functional tolerance, and broad substrate scope.

Photochemical ring expansion reactions: synthesis of tetrahydrofuran derivatives and mechanism studies.

The reaction mechanism of oxygen and sulfur ylide mediated rearrangements is even today a matter of debate. In this report, we describe ring expansion reactions of oxetane and thietane heterocycles that allow probing the underlying reaction mechanism under metal-free, photochemical conditions. This ring expansion proves highly efficient and allows the synthesis of tetrahydrofuran and thiolane heterocycles under mild and operationally simple reaction conditions. These studies reveal marked differences in the stereoselectivity of the ring expansion of oxygen or sulfur ylides, which were further investigated computationally. DFT calculations show that carbenes react under ylide formation and that the corresponding ring expansion reactions proceed via a diradical pathway. The different bond lengths in free oxygen or sulfur ylide intermediates cause the distinctive stereochemical outcome.

Ligand-modulated ring-expansion.

An unstrained palladium-containing macrocycle was expanded by a ring-opening metathesis strategy. This reaction was driven by coordination of a bulky ligand, 2,6-lutidine, to the palladium center, enabling a monometallic macrocycle to transform into a bimetallic dimeric macrocycle.

Sequential cycloaddition and ring expansion reaction of arynes and methylenebenzothiopheneones: synthesis of a benzo-fused eight-membered ring via sulfonium ylides.

A sequential cycloaddition and ring expansion of arynes and methylenebenzothiopheneones has been disclosed. This strategy proceeds through a sulfonium ylides intermediate and allows for the efficient synthesis of a sulfur-containing benzo-fused eight-membered ring.

Insights into highly selective ring expansion of oxaziridines under Lewis base catalysis: a DFT study

The possible mechanism and stereoselectivity of the NHC-catalyzed ring expansion reaction of oxaziridines have been theoretically studied for the first time.

Mn(III)-Based Oxidative Radical Ring-Expansion Reaction Using Squarate Derivatives: Selective Synthesis of Bis(butenolide)s and the Acetate Monomers

Mn(III)-Based Oxidative Radical Ring-Expansion Reaction Using Squarate Derivatives: Selective Synthesis of Bis(butenolide)s and the Acetate Monomers

Rethinking Hydrolytic Imidazoline Ring Expansion: A Common Approach to the Preparation of Medium-Sized Rings via Side-Chain Insertion into [1.4]Oxa- and [1.4]Thiazepinone Scaffolds.

The previously reported ring-expansion strategy involving hydrolytically prone imidazoline rings was thought to include the formation of a hydrated imidazoline intermediate. In this work, we accessed the latter via the addition of a 2-aminoethyl side chain onto a lactam moiety. This led to an efficient three-atom ring expansion of diarene-fused [1.4]oxazepines and [1.4]thiazepines and led us to propose to term this common approach the hydrated imidazoline ring expansion (HIRE) reaction. The strategy was extended to the insertion of longer (containing up to five atoms) side chains, and thus, larger (11- to 12-membered) diarene-fused rings were obtained via the homo-HIRE and homo2-HIRE reactions, respectively. This underscores the utility of the HIRE reaction for the preparation of medium-sized rings, an important class of chemical tools for interrogation of various biological targets.

1,2,3-Diazaborinine: A BN Analogue of Pyridine Obtained by Ring Expansion of a Borole with an Organic Azide.

A new pathway for the ring expansion reaction of antiaromatic boroles with organic azides is reported. While the reaction usually leads to 1,2-azaborinines, it was diverted to the formation of a 1,2,3-diazaborinine by changing the electronic characteristics of the reagents. The isolable azo-azaborinine intermediate initially formed from the reaction of 1-(2,3,4,5-tetraphenylborolyl)ferrocene with 4-azido-N,N-dimethylaniline gradually decomposed to a 1,2,3-diazaborinine and benzonitrile. Both the spectroscopic properties and the reactivity of the heteroaromatic compound show analogies to pyridine, to which it is isoelectronic. Density functional theory (DFT) calculations provided insight into the mechanism of this unusual transformation.

Antiviral drug nevirapine as a template for hydrated imidazoline ring expansion (HIRE): Rapid access to the diarene-fused 1,4,7-triazecine ring system

The tricyclic ring system of the antiviral drug nevirapine has been employed to test the workability of the hydrated imidazoline ring expansion (HIRE) reaction which was previously exemplified for [1.4]oxazepine and [1.4]thiazepine counterparts. The imidazoline nucleus was grafted onto the lactam moiety of nevirapine in two high-yielding steps. Subsequent N-alkylation and the HIRE reaction proceeded as envisioned and delivered rare ring-expanded diarene-fused 1,4,7-triazecines with a diversity of alkyl substituents at the lactam nitrogen atom. These findings extend the scope of the HIRE reaction to the medicinally prominent [1.4]diazepine chemical space.

Microbial transformation of the anti-aging agent cycloastragenol by Mucor racemosus

The microbial transformation of cycloastragenol (CA) by Mucor racemosus AS 3.20 was investigated. Seven isolated products were identified as (20R,24S)-3β,6α,16β,25- tetrahydroxy-20,24-epoxy-9,10-seco-cycloartan-9(11),10(19)-diene (1), (20R,24S)- 3β,6α,16β,25-tetrahydroxy-20,24-epoxy-9,10-seco-cycloartan-1(10),9(11)-diene (2), (20R,24S)-3β,16β,25-trihydroxy-6α,19α;20,24-diepoxy-9,10-seco-cycloartan-9(11)-ene (3), (20R,24S)-6α,16β,25-trihydroxy-3β,10β;20,24-diepoxy-9,10-seco- cycloartan-11-one (4), (20R,24S)-16β,25-dihydroxy-6α-methoxy-3β,10β;20,24- diepoxy-9,10-seco-cycloartan-7(8),9(11)-diene (5), (20R,24S)-6α,16β,25-trihydroxy-3β,10β;20,24-diepoxy-9,10-seco-cycloartan-9(11)-ene (6), and (20R,24S)-3β,6α,16β,25-tetrahydroxy-19-acetoxy-ranunculan-9(10)-ene (7) by spectroscopic analysis. Among them, compounds 2 and 5 were new compounds. M. racemosus could catalyze ring expansion and epoxidation reactions to form 3β,10β-epoxy- or 6α,19α-epoxy-9,10-seco-cycloartane structures. These regio- and stereo-selective reactions are difficult to achieve by chemical means. In addition, the biological effects of isolated metabolites on increasing the lifespan of Caenorhabditis elegans were evaluated. Most of the metabolites could significantly extend the lifespan of C. elegans at 50 μM.

Iterative Assembly of Macrocyclic Lactones using Successive Ring Expansion Reactions.

Macrocyclic lactones can be prepared from lactams and hydroxyacid derivatives via an efficient 3‐ or 4‐atom iterative ring expansion protocol. The products can also be expanded using amino acid‐based linear fragments, meaning that macrocycles with precise sequences of hydroxy‐ and amino acids can be assembled in high yields by “growing” them from smaller rings, using a simple procedure in which high dilution is not required. The method should significantly expedite the practical synthesis of diverse nitrogen containing macrolide frameworks.

Hydride Amide and Hydride Phenolate Complexes of NHC Coordinated Aluminum

The reaction of NHC alane adducts NHC·AlH3 (NHC = N‐Heterocyclic Carbene; NHC = iPr2Im, Dipp2Im; R2Im = 1,3‐di‐organyl‐imidazolin‐2‐ylidene; iPr = isopropyl; Dipp = 2,6‐diisopropylphenyl) with secondary amines HNR2 [R = iPr, Ph, Si(CH3)3] and the reaction of the trimethylamine alane adduct (NMe3)·AlH3 with secondary amines followed by the reaction with the NHC both lead to formation of the compounds NHC·AlH2(NR2) 1–6 [NHC = iPr2Im, Dipp2Im, R = iPr, Ph, Si(CH3)3]. These compounds are stable in solution up to temperatures of 90 °C. In contrast to the NHC alane adduct (iPr2Im)·AlH3 (I) and (Dipp2Im)·AlH3 (II), no ring expansion reaction to six‐membered heterocyclic rings or ring opening reaction were observed for the reaction of (iPr2Im)·AlH2(NR2) with another equivalent of the NHCs iPr2Im or Dipp2Im. Thus, amide substituted NHC alane adducts show a much high stability compared to the parent compounds NHC·AlH3. Furthermore, the reaction of NHC·AlH3 (NHC = iPr2Im, Dipp2Im) with 2,4,6‐trimethylphenol leads to the formation of the adducts NHC·AlH3–n(OMes)n 7–10 (n = 1, 2). The reaction with n ≥ 3 equivalent of 2,4,6‐trimethylphenol afforded the imidazolium salt [Dipp2ImH]+[Al(OMes)4]– (11). The compounds 7–11 are also stable with respect to ring expansion after addition of another equivalent NHC.

Ring-Expansion/Contraction Radical Crossover Reactions of Cyclic Alkoxyamines: A Mechanism for Ring Expansion-Controlled Radical Polymerization.

Macrocyclic polymers present an important class of macromolecules, displaying the reduced radius of gyration or impossibility to entangle. A rare approach for their synthesis is the ring expansion-controlled radical “vinyl” polymerization, starting from a cyclic alkoxyamine. We here describe ring-expansion radical crossover reactions of cyclic alkoxyamines which run in parallel to chain-propagation reactions in the polymerization system. The radical crossover reactions extensively occurred at 105–125 °C, eventually producing high molecular weight polymers with multiple inherent dynamic covalent bonds (NOC bonds). A subsequent ring-contraction radical crossover reaction and the second ring-expansion radical crossover reaction are also described. The major products for the respective three stages were shown to possess cyclic morphologies by the molecular weight profiles and the residual ratios for the NOC bonds (φ in %). In particular, the high φ values ranging from ca. 80% to 98% were achieved for this cyclic alkoxyamine system. This result verifies the high availability of this system as a tool demonstrating the ring-expansion “vinyl” polymerization that allows them to produce macrocyclic polymers via a one-step vinyl polymerization.

Regioselective Ring Expansion of Isatins with In Situ Generated α-Aryldiazomethanes: Direct Access to Viridicatin Alkaloids.

A novel efficient one-pot regioselective ring-expansion reaction of isatins with in situ generated α-aryl/heteroaryldiazomethanes for the construction of viridicatin alkaloids has been described under metal-free conditions. The utility of this protocol is further demonstrated in the synthesis of naturally occurring viridicatin, viridicatol, and substituted 3- O-methyl viridicatin and their scale up.

Conversion of Methylcyclopentane (MCP) on Pt-Mo/AlPO<sub>4</sub> Catalyst

The effect of platinum and reaction temperature was investigated in the conversion of methylcyclopentane (MCP) with hydrogen at atmospheric pressure. The dispersed 0,5wt% Pt on AlPO4 (PtAlP), and Mo/AlPO4 (PtMoAlP) metal catalysts were prepared by incipient wetness impregnation or co-impregnation methods. The most active catalyst in the conversion of MCP was PtAlP and the most selective to MCP ring opening was PtMoAlP. High temperature promoted ring opening at the secondary–tertiary positions, which was attributed to the adlineation sites. At low temperatures, PtMoAlP promoted only the ring enlargement reaction while PtAlP promoted both ring opening and ring enlargement. Ring enlargement of MCP to cyclohexane and benzene was catalysed by electron deficient adduct sites, while ring opening to 2-meythylpentane (2-MP), 3methylpentane (3-MP) and n-hexane (n-H) was catalysed by metallic sites. At high temperatures, MCP broken into C1–C5 fragments and deactivation of the catalysts was observed.

Recent Advances in the Cycloisomerizations of Methylenecyclopropanes using Gold Catalysis.

During the past decades, cycloisomerizations of methylenecyclopropanes using gold catalysis have attracted much attention from organic chemists. The different patterns of gold(I)-catalyzed cycloisomerizations of methylenecyclopropanes have been developed, and they can be classified as ring-opening and ring-expansion reaction patterns. This synthetic methodology provides a new approach to novel cyclic- or polycyclic compounds. The corresponding products have great potential for material science, medicinal chemistry and total synthesis. This Concept article will mainly focus on the recent advances in the cycloisomerizations of methylenecyclopropanes in the past four years.

Ring Expansion, Ring Contraction, and Annulation Reactions of Allylic Phosphonates under Oxidative Cleavage Conditions.

Oxidative cleavage of cycloalkenylalkylphosphonates 1 followed by treatment with base gives rise to homologated cycloalkenones 2 in good to excellent yields. Subjecting cycloalk-2-enylphosphonates 3 to identical conditions provides the one-carbon ring-contracted compounds 4 in excellent yields. Oxidative cleavage of γ,δ-unsaturated ketophosphonates 6 followed by treatment with base affords 2-cyclopenten-1-ones 7 in good overall yields. This method may offer a practical alternative to existing methods for effecting one-carbon ring expansion, ring contraction, and annulation reactions.

Biotransformation of cyclocanthogenol by the endophytic fungus Alternaria eureka 1E1BL1

The microbial transformation of cyclocanthogenol (CCG), Astragalus sp. originated sapogenin, by the endophytic fungus Alternaria eureka 1E1BL1 isolated from Astragalus angustifolius was investigated. Hydroxylation, oxidation, epoxidation, O-methylation, ring-expansion and methyl migration reactions were observed on the triterpenoid skeleton. As a result, eight metabolites were isolated and the structures of the previously undescribed compounds were established by 1-D, 2-D NMR and HR-MS analyses.

Synthesis of Benzo[1,4]thiazines via Ring Expansion of 2-Aminobenzothiazoles with Terminal Alkynes Under Metal–Organic Framework Catalysis

Copper–organic framework Cu–MOF-74 was synthesized, and consequently utilized as a heterogeneous catalyst for the synthesis of benzo[1,4]thiazines via ring expansion of 2-aminobenzothiazoles with terminal alkynes. Different from previous works, the reaction proceeded readily in the presence of lower catalyst concentration, at lower temperature, and under ligand-free conditions. The combination of 5 mol% framework catalyst, 20 mol% Cs2CO3, and 3 equivalents of di-tert-butyl peroxide led to high yields of benzo[1,4]thiazines. This copper-based framework demonstrated higher catalytic efficiency than a series of MOF-based heterogeneous catalysts and traditional homogeneous catalysts. In this system, the donation of soluble active copper species to the formation of benzo[1,4]thiazines was trivial. The copper–organic framework was reutilized without a remarkable decline in catalytic efficiency. To our best knowledge, this ring expansion reaction was not previously performed with a recyclable catalyst.

Transition-Metal-Free Ring Expansion Reactions of Indene-1,3-dione: Synthesis of Functionalized Benzoannulated Seven-Membered Ring Compounds.

A novel ring expansion reaction of indene-1,3-dione with alkynyl ketones under transition-metal-free conditions has been developed. This process offers an efficient and direct way to synthesize benzoannulated seven-membered rings or fused-ring compounds through C-C σ-bond activation. Notable features of the procedure include easily accessible starting materials, good functional group tolerance, and high atom economy.