Relative thermodynamic stabilities of the isomeric dihydrofurans and isomeric dihydropyrans. An experimental and DFT study

The relative thermodynamic stabilities of 2,5-dihydrofuran (1) and 2,3-dihydrofuran (2), and of 3,4-dihydro-6H-pyran (3) and 3,4-dihydro-2H-pyran (4), were determined at several temperatures by base-catalyzed equilibration in DMSO solution. For 1 → 2, = –15.4±0.1 kJ mol⁻¹, =–12.6±0.5 kJ mol⁻¹, and =9.5±1.3 J K⁻¹ mol⁻¹ at 298.15 K. The second-law reaction enthalpy agrees with literature data based on calorimetric enthalpies of hydrogenation of the isomeric forms in hexane. For 3 → 4, =–19.3±0.2 kJ mol⁻¹, = –18.9±1.1 kJ mol⁻¹ and =1.1±3.0 J K⁻¹ mol⁻¹ at 298.15 K: the experimental reaction enthalpy is in marked disagreement with literature data based on estimation. On the other hand, both of the experimental reaction enthalpies of the present study are in good agreement with DFT calculations using the B3LYP functional and 6-311+G(2d,p) basis set.     

Ring-rearrangement metathesis of bicyclic amino acid derivatives

In this letter, we describe the ring-rearrangement metathesis (RRM) of bicyclic amino acid derivatives. The procedure is of use for the synthesis of constrained amino acid and peptide derivatives with potential as reverse-turn inducers.     

Ring-rearrangement metathesis of 3,6-dialkoxy-3,6-dihydro-2H-pyrans

The first RCM-ROM-RCM sequence using a non-strained heterocycle as relay moiety is described. The course of the reaction strongly depends on the nature and relative configuration of the substituents in the starting trienic system. In addition, for a productive reaction to be observed, the site of initiation of the metathesis cascade is crucial. The compounds thus obtained may be useful for the synthesis of unusual polydeoxydisaccharides.     

Ring-rearrangement metathesis of nitroso Diels-Alder cycloadducts

Strained nitroso Diels–Alder bicyclo[2.2.1] or [2.2.2] adducts functionalized with alkene side chains of diverse length undergo a ring‐rearrangement metathesis process with external alkenes and Grubbs II or Hoveyda–Grubbs II ruthenium catalysts, under microwave irradiation or classical heating, to deliver cis‐fused bicycles of various ring sizes, which contain a N? O bond. These scaffolds are of synthetic relevance for the generation of molecular diversity and to the total synthesis of alkaloids. The observation of unexpected reactions, such as epimerization or one‐carbon homologation of the alkene side chain, is also reported.     

Facile synthesis of polysubstituted furans and dihydrofurans via cyclization of bromonitromethane with oxodienes

A series of polysubstituted furans and dihydrofurans have been prepared from readily available oxodienes and bromonitromethane in modest to excellent yields. This facile synthetic method is developed on the basis of proprietary properties of nitro group such as strong electron-withdrawing ability and cleavability. The conversion of nitro-substituted dihydrofurans to furans is presumably realized by elimination of HNO₂ under the aid of DABCO.     

Excellent treatment activity of biscoumarins and dihydropyrans against P. aeruginosa pneumonia and reinforcement learning for designing novel inhibitors

Pseudomonas aeruginosa (P. aeruginosa) is a common clinical pathogen, which can easily cause cystic fibrosis and even bacteremia. In recent years, the antibiotic resistance of P. aeruginosa has been increasing. In an attempt to develop novel antibacterial agents, a series of biscoumarins (1–5) and dihydropyrans (6–10) were successfully prepared. The molecular structures of two representative compounds, that is, 1 and 6 were confirmed by single crystal X-ray diffraction study. The anti-bacterial activity of these synthesized compounds in vitro was evaluated by measuring the MIC values, as well as the P. aeruginosa growth curves. Next, the in vivo treatment activity of these compounds against the P. aeruginosa pneumonia infection was assessed by observing the survival rate of the infected mice and counting the bacterial load with colony plate counting assay. Additionally, the ELISA detection was conducted to evaluate the inflammatory response levels by measuring the IL-1β and TNF-α content released into the plasma, nasal lavage fluid and alveolar lavage fluid. The HE staining was also carried out to detect the protective effect of the compounds on the lung tissue damage. Further, novel anti-bacterial structures that are based on biscoumarin 5 are predicted and evaluated using reinforcement learning technic, and two outstanding pharmaceutical structures with low binding energy and high SA and QED scores are analyzed in detail using molecular docking simulation.     

Efficient synthesis of enantiomerically pure dihydropyrans

cis- and trans-2-Substituted-3,6-dihydro-2H-pyran-3-ols have been prepared via an aldol condensation/ring-closing metathesis/enzymatic resolution sequence. The process can be scaled up to yield gram quantities of enantiomerically pure material.     

Allenyl esters as quenching agents for ruthenium olefin metathesis catalysts

In the attempt to synthesize substituted allenyl esters through a metathesis coupling of unsubstituted allenyl esters and alkenes using a variety of ruthenium catalysts, it was discovered that allenyl esters themselves cleanly arrested the activity of the catalysts. Further studies suggests possible utility of allene esters as general quenching agents for metathesis reactions. To explore this idea, several representative olefin metathesis reactions, including ring closing, were successfully terminated by the addition of simple allenyl esters for more convenient purification.     

Alkoxy group facilitated ring closing metathesis (RCM) of acyclic 1,6-dienes. Convenient synthesis of non-racemic highly substituted cyclopentenols

Alkoxymethyl groups at the C-5 allylic position of 1,6-dienols have been found to accelerate RCM reactions significantly with the Grubbs’ catalyst PhCHRu(PCy₃)₂Cl₂. This phenomenon has been used for direct access to highly substituted cyclopentenols, potential intermediates in the synthesis of carbovir, abacavir and BCA.     

Diastereoselective ring-closing metathesis in the synthesis of dihydropyrans

An investigation into the factors influencing the diastereochemical outcome of the ring-closing metathesis based synthesis of dihydropyrans is presented in this paper. Divinyl carbinols derived from alpha-hydroxy carboxylic acid esters are elaborated to trienes with two diastereotopic vinyl moieties. Depending on the steric demand of the oxo substituent of the divinyl carbinol moiety (either unprotected OH, TBDMS, or benzyl ether) different diastereomers are preferrably formed upon ring-closing metathesis. An extension to diastereoselective double ring-closing metathesis in the formation of spirocycles has also been investigated.     

An efficient approach to the stereoselective synthesis of 2,6-disubstituted dihydropyrans via stannyl-Prins cyclization

A general method has been developed for the stereoselective construction of 2,6-disubstituted dihydropyrans based on the Lewis acid-catalyzed intramolecular reactions of oxocarbenium ions with vinylstannanes. This novel methodology was applied to the enantioselective total synthesis of (−)-centrolobine.     

Polymer-supported selenium-induced electrophilic cyclization: solid-phase synthesis of poly-substituted dihydrofurans and tetrahydrofurans

Poly-substituted dihydrofurans and tetrahydrofurans have been synthesized through polymer-supported selenium-induced intramolecular electrophilic cyclization, followed by selenoxide syn-elimination or novel nucleophilic substitution cleavage of selenium resin with good yields and purities.     

Synthesis of 2,6-dioxabicyclo[3.3.0]octenes by tandem ring-rearrangement/cross metathesis

A facile synthesis of stereodefined 2,6-dioxabicyclo[3.3.0]octene derivatives from the vinyl ether of endo-7-oxanorbornen-2-ol via tandem ring-opening/ring-closing(ring-rearrangement)/cross metathesis is reported.     

Synthesis of dienynes from alkenes and diynes using ruthenium-mediated ring-closing metathesis

This communication describes a novel ruthenium-mediated transformation, which converts molecules containing alkenes and conjugated diynes such as 1-allyl-2-{[6-(2-allylphenoxy)-2,4-hexadiynyl]oxy}benzene into dienynes such as 3-[2-(2,5-dihydro-1-benzoxepin-3-yl)-1-methylene-2-propenyl]-2,5-dihydro-1-benzoxepine instead of the expected product 3-[2-(2,5-dihydro-1-benzoxepin-3-yl)ethynyl]-2,5-dihydro-1-benzoxepine.     

A facile synthesis of highly functionalized dihydrofurans based on 1,4-diazabicyclo[2.2.2]octane (DABCO) catalyzed reaction of halides with enones

Treatment of halides 5 with electrophilic alkenes 2 afforded the corresponding dihydrofurans 3 and 4 in the presence of 1, 4-diazabicyclo[2.2.2]octane (DABCO) with good to excellent yields and in a stereoselective manner in most cases. Moreover, the stereoisomers 3 and 4 could be easily transformed each other in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).     

A versatile synthesis of carbapenems from substituted dihydropyrans

Dihydropyrans (1) are converted by hydrolysis and reduction to δ-lactones (3), and then to azetidinones (5) which are key intermediates for the synthesis of carbapenems.     

Facile syntheses of substituted 2,3-dihydrofurans and benzofurans by palladium-catalyzed reactions of propargylic carbonates with nucleophiles

Substituted 2,3-dihydrofurans and benzofurans are synthesized by the palladium-catalyzed reaction of 5-methoxycarbonyloxy-3-pentyn-1-ols and 1-(2-hydroxyphenyl)-3-methoxycarbonyloxy-1-propyne with nucleophiles, respectively. Various substituted propargylic carbonates and nucleophiles are efficiently transformed to their corresponding products. Additionally, a reaction using substrates containing a nucleophilic phenoxy group within the same molecule also produces the corresponding dihydrofuran.     

Applications of metathesis in heterogeneous catalysis and separation sciences

During the last 15 years, the area of well-defined metathesis initiator systems was characterized by almost dramatic improvements in terms of initiator activity, stability, and selectivity. In due consequence, control over polymer properties increased and metathesis-based polymerization techniques (in particular ring-opening metathesis polymerization, ROMP) have been adapted for materials science purposes. Quite recently, metathesis-based supports have entered the fields of heterogeneous catalysis as well as separation and life sciences. In this review, both the synthesis and properties of metathesis-based well-defined catalytic supports and separations systems shall be summarized. Special consideration will be given to the particular structural features that have been made possible using ROMP.     

Ring-closing olefin metathesis reactions; synthesis of iso-β-bisabolol

A ring-closing olefin metathesis is the key step in a synthesis of the rare iso-β-bisabolol found in sandalwood oils.