Search

The ring‐expansion of arylthiiranes and phenoxyacetyl chloride was performed in the presence of triethylamine and provided a novel strategy for the synthesis of 4,5‐dihydrobenzo[d]thiepin‐2(1H)‐ones, benzo[d]‐ϵ‐thiolactones, directly without catalysts or additives. Its linear free energy analysis was conducted on the basis of competitive experiments. The results indicate that both reaction constants are close to zero (0.14 for σm and 0.20 for σp), supporting the proposed sulfur‐shifted ene mechanism. The current reaction features atom and step‐economic one‐pot characteristic via a tandem sequence of in situ ketene generation, sulfur‐shifted ene reaction, and aromatization. [ABSTRACT FROM AUTHOR]

Quantum chemical calculations are reported for the thermal dimerizations of 1,3-cyclohexadiene at 1 atm and high pressures up to the GPa range. Computed activation enthalpies of plausible dimerization pathways at 1 atm agree well with the experiment activation energies and the values from previous calculations. High-pressure reaction profiles, computed by the recently developed extreme pressure-polarizable continuum model (XP-PCM), show that the reduction of reaction barrier is more profound in concerted reactions than in stepwise reactions, which is rationalized on the basis of the volume profiles of different mechanisms. A clear shift of the transition state towards the reactant under pressure is revealed for the [6+4]-ene reaction by the calculations. The computed activation volumes by XP-PCM agree excellently with the experimental values, confirming the existence of competing mechanisms in the thermal dimerization of 1,3-cyclohexadiene.

Here we present a catalyst‐free protocol for the purple light‐mediated anti‐Markovnikov functionalization of alkenes with thiols. Crucial to the generation of the thiyl radical was the formation of a key photo‐active complex. More than 30 thioether products were obtained, demonstrating tolerance towards different functional groups and scalability up to 5 mmol of alkene. Two different reaction conditions have been developed, varying both the solvent and the amount of thiol. Depending on the alkene structure, water can be used as an alternative to dichloromethane as a solvent, thus increasing the sustainability of the whole process. [ABSTRACT FROM AUTHOR]

The reaction of pulegone with 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione as enophile gives two known epimers, 1-[(1R,4R)-4-methyl-2-oxo-1-(prop-1-en-2-yl)cyclohexyl]-4-phenyl-1,2,4-triazolidine-3,5-dione (RR isomer) and 1-[(1S,4R)-4-methyl-2-oxo-1-(prop-1-en-2-yl)cyclohexyl]-4-phenyl-1,2,4-triazolidine-3,5-dione (SR isomer). In addition, we isolated previously unknown 1-{2-[(4R)-4-methyl-6-oxocyclohex-1-en-1-yl]propan-2-yl}-4-phenyl-1,2,4-triazolidine-3,5-dione. According to the results of quantum chemical simulation, the isomeric products of hydrogen substitution in pulegone by the enophile are formed along three pathways. The SR isomer is formed via a concerted ene reaction. The other two channels involve approach of the enophile from the R side of pulegone and include two consecutive steps. The first step generates intermediate unsymmetrical cyclic aziridine cation, and elimination of proton from one of the geminal methyl groups of that intermediate yields the RR isomer with a terminal double bond. Proton elimination from methylene group of the pulegone fragment gives a cyclic compound with internal double bond. The ratio of the isomer with internal double bond and the RR isomer depends on the polarity of aprotic solvent. [ABSTRACT FROM AUTHOR]

The assembly of enzymatic cascades and multi‐step reaction sequences represents an attractive alternative to traditional synthetic‐organic approaches. The biocatalytic reaction mediators offer not only mild conditions and permit the use of environmentally benign reagents, but the high compatibility of different enzymes promises more streamlined reaction setups. In this study, a triple‐enzymatic strategy was developed that enables the direct conversion of γ,δ‐unsaturated esters to N‐hydroxy‐γ‐lactam building blocks. Hereby, a lipase‐catalyzed hydroxylaminolysis generates hydroxamic acid intermediates that are subsequently aerobically activated by horseradish peroxidase and glucose oxidase to cyclize in an intramolecular nitroso ene reaction. Utilizing the hydroxylaminolysis/ene‐cyclization sequence for the preparation of an aza‐spirocyclic lactam, the multi‐enzymatic methodology was successfully employed in the synthesis of key intermediates en route to alkaloids of the Cephalotaxus family. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The application of reversible degenerative radical polymerization (RDRP) in the construction of polymer networks (PNs) provides a facile and convenient way to fabricate 3D objects with the ability to be posttransformed. However, the polymerization mechanism mainly relies on chain‐growth polymerization, which limits its wide application for various polymeric materials with different functionalities. Here, we present a method toward PNs by utilizing a photoinduced RAFT step‐growth polymerization, which is based on a RAFT single unit monomer insertion (SUMI) reaction between a xanthate and an alkyl vinyl group. Benefiting from this reaction, a pendant RAFT agent can be generated in each repeat unit of the backbone during the polymerization. These reactivatable dormant species can be further used for the postfunctionalization of PNs prepared by step‐growth polymerization of multifunctional monomers. Moreover, the prepared PNs are degradable owing to the introduction of ester groups, providing an avenue toward degradable and stimuli‐responsive materials. [ABSTRACT FROM AUTHOR]

The biocatalytic oxidation of acylated hydroxylamines enables the direct and selective introduction of nitrogen functionalities by activation of allylic C−H bonds. Utilizing either laccases or an oxidase/peroxidase couple for the formal dehydrogenation of N‐hydroxycarbamates and hydroxamic acids with air as the terminal oxidant, acylnitroso species are generated under particularly mild aqueous conditions. The reactive intermediates undergo C−N bond formation through an ene‐type mechanism and provide high yields both in intramolecular and intermolecular enzymatic aminations. Investigations on different pathways of the two biocatalytic systems and labelling studies provide more insight into this unprecedented promiscuity of classical oxidoreductases as catalysts for nitroso‐based transformations. [ABSTRACT FROM AUTHOR]

Vegetable oils are bio−based and sustainable starting materials that can be used to develop chemicals for industrial processes. In this study, the functionalization of three vegetable oils (grape, hemp, and linseed) with maleic anhydride was carried out either by conventional heating or microwave activation to obtain products that, after further reactions, can enhance the water dispersion of oils for industrial applications. To identify the most abundant derivatives formed, trans-3-octene, methyl oleate, and ethyl linoleate were reacted as reference systems. A detailed NMR study, supported by computational evidence, allowed for the identification of the species formed in the reaction of trans-3-octene with maleic anhydride. The signals in the 1H NMR spectra of the alkenyl succinic anhydride (ASA) moieties bound to the organic chains were clearly identified. The reactions achieved by conventional heating were carried out for 5 h at 200 °C, resulting in similar or lower amounts of ASA units/g of oil with respect to the reactions performed by microwave activation, which, however, induced a higher viscosity of the samples. [ABSTRACT FROM AUTHOR]

A variety of highly functionalized allenes and allenamides are prepared by intramolecular propargylic ene reactions of benzynes. Specific benzyne precursors having a chlorodiisopropylsilyl group serve as platforms to link with various propargyl alcohols via a Si–O bond, thereby expanding the scope of this reaction. Also demonstrated is a complete transmission of point to axial chirality to give a chiral, non-racemic allenamide. [ABSTRACT FROM AUTHOR]

Intermolecular aryne ene reactions present opportunities to arylate a wide range of unsaturated substrates in a single step, whilst intramolecular reactions provide expedient access to valuable benzofused carbo- and heterocyclic frameworks. This short review will chart the development of the aryne ene reaction from initial reports that rationalise unexpected byproduct formation in competing [4+2] and [2+2] cycloadditions through to its exploitation in contemporary synthetic methodology. 1 Introduction 2 Alkene Ene Reactions 2.1 Intermolecular 2.2 Intramolecular 3 Alkyne Ene Reactions 3.1 Intermolecular 3.2 Intramolecular 4 Allene Ene Reactions 5 Aromatic Ene Reactions 6 Hetero Ene Reactions 6.1 Enols 6.2 Enamines 6.3 Imines 7 Conclusions [ABSTRACT FROM AUTHOR]

Iriomoteolide-1a and iriomoteolide-1b are very potent cytotoxic agents, isolated from marine dinoflagellates. We carried out the enantioselective syntheses of the proposed structures of these natural products. However, our analysis of the NMR spectra of the synthetic iriomoteolide-1a and the natural products revealed that the structures of iriomoteolide-1a and iriomoteolide-1b were assigned incorrectly. Based upon our detailed analysis of the spectral data of the synthetic iriomoteolide-1a and the natural products, we rationally designed three diastereomers of the proposed structure of 1 in an effort to assign the correct structures. The key steps of our syntheses of the proposed structures of iriomoteolides involved a highly diastereoselective ene reaction, a carbocupration that utilized a Gilman reagent, a Julia–Kocienski olefination to couple fragments, and Yamaguchi macrolactonization to form the target macrolactone. This synthetic route was then utilized to carry out syntheses of three diastereomers to the proposed structure of 1. These diastereomeric structures show close similarities to natural iriomoteolide-1a; however, there were differences in their spectral data. While natural iriomoteolides exhibited potent cytotoxicies, our preliminary biological evaluation of synthetic iriomoteolide-1a, iriomoteolide-1b, and all three synthetic derivatives did not show any appreciable cytotoxic properties. [ABSTRACT FROM AUTHOR]

This synthesis enabled a gram-scale preparation of avicholic acid in only 10 steps and with 16% overall yield from the cheap, industrial material dehydroepiandrosterone (DHEA) via an easy and efficient ene reaction as the key step. [Display omitted] A 10-step synthesis of the unique C16-hydroxylated bile acid natural product avicholic acid from cheap, industrial material dehydroepiandrosterone (DHEA) is reported. This synthesis features an improved four-step sequence for the construction of the known 3α,7α-dihydroxy-5β-androstan-17-one, and a practical installation of C16α-OH through the key functionalization on ring D via an easy and efficient ene reaction, which enables a gram-scale preparation of avicholic acid in only 10 steps and with 16 % overall yield. [ABSTRACT FROM AUTHOR]

The reactivity of N‐tosyl vinylaziridines toward arynes has been demonstrated under mild and transition‐metal‐free conditions to yield 2‐(phenanthren‐9‐yl)ethan‐1‐sulfamides in moderate to good yields. The selective synthesis of N‐H and N‐aryl products was accomplished using CsF in MeCN and KF/18‐C‐6 in 1,4‐dioxane, respectively. This cascade process involves a sequential Diels‐Alder reaction, ring‐opening aromatization, ene‐reaction, and selective N‐arylation reaction. [ABSTRACT FROM AUTHOR]

The catalytic effect of various Lewis acids (LAs) on the ene reaction between propene (ene) and but‐3‐en‐2‐one (enophile) was studied quantum chemically using density functional theory and with coupled‐cluster theory. The studied LAs efficiently accelerate the ene reaction by lowering the reaction barrier up to 12 kcal mol−1 compared to the uncatalyzed reaction. Our detailed activation strain and Kohn‐Sham molecular orbital analyses reveal that coordination of a LA catalyst to the enophile decreases the reaction barrier of the ene reaction by inducing an asymmetry in the π‐electronic system, which increases the asynchronicity and hence relieves the otherwise highly destabilizing activation strain and Pauli repulsion between the closed‐shell filled π‐orbitals of the ene and enophile. In all, these findings further demonstrate the generality of the Pauli‐lowering catalysis concept. [ABSTRACT FROM AUTHOR]

Vegetable oils are bio−based and sustainable starting materials that can be used to develop chemicals for industrial processes. In this study, the functionalization of three vegetable oils (grape, hemp, and linseed) with maleic anhydride was carried out either by conventional heating or microwave activation to obtain products that, after further reactions, can enhance the water dispersion of oils for industrial applications. To identify the most abundant derivatives formed, trans-3-octene, methyl oleate, and ethyl linoleate were reacted as reference systems. A detailed NMR study, supported by computational evidence, allowed for the identification of the species formed in the reaction of trans-3-octene with maleic anhydride. The signals in the 1H NMR spectra of the alkenyl succinic anhydride (ASA) moieties bound to the organic chains were clearly identified. The reactions achieved by conventional heating were carried out for 5 h at 200 °C, resulting in similar or lower amounts of ASA units/g of oil with respect to the reactions performed by microwave activation, which, however, induced a higher viscosity of the samples.

Iriomoteolide-1a and iriomoteolide-1b are very potent cytotoxic agents, isolated from marine dinoflagellates. We carried out the enantioselective syntheses of the proposed structures of these natural products. However, our analysis of the NMR spectra of the synthetic iriomoteolide-1a and the natural products revealed that the structures of iriomoteolide-1a and iriomoteolide-1b were assigned incorrectly. Based upon our detailed analysis of the spectral data of the synthetic iriomoteolide-1a and the natural products, we rationally designed three diastereomers of the proposed structure of 1 in an effort to assign the correct structures. The key steps of our syntheses of the proposed structures of iriomoteolides involved a highly diastereoselective ene reaction, a carbocupration that utilized a Gilman reagent, a Julia–Kocienski olefination to couple fragments, and Yamaguchi macrolactonization to form the target macrolactone. This synthetic route was then utilized to carry out syntheses of three diastereomers to the proposed structure of 1. These diastereomeric structures show close similarities to natural iriomoteolide-1a; however, there were differences in their spectral data. While natural iriomoteolides exhibited potent cytotoxicies, our preliminary biological evaluation of synthetic iriomoteolide-1a, iriomoteolide-1b, and all three synthetic derivatives did not show any appreciable cytotoxic properties.

The different reactivity of trienones under Lewis and Brønsted acids catalysis was investigated, resulting in distinct cyclization products and carbon backbones that originated either from a conjugate Prins cyclization or an interrupted Nazarov cyclization. In particular, an unprecedented Nazarov cyclization tandem reaction is presented, terminating the oxyallyl cation by an ene‐type reaction, and leading stereoselectively to bicyclic spiro compounds. The terminal olefin of this motif represents a useful handle for further functionalization, making it a strategic intermediate in total syntheses. The tandem Nazarov/ene cyclization was shown to be preferred over a Nazarov/[3+2] tandem reaction for all our substrates, independent of chain length. Deuteration studies further support the mechanistic hypothesis of the terminating ene reaction. [ABSTRACT FROM AUTHOR]

[Display omitted] 6/6/5/7 Tetracyclic core of Swinhoeisterol A was constructed starting from Wieland-Miescher ketone and silylated ethyl 5–hydroxyvalerate. After modification, the bicyclic and linear subunits were assembled by means of cross-metathesis reaction. Then, cyclopentane C ring was formed by the intramolecular aldol condensation. C17-stereocenter was constructed using Claisen rearrangement followed by the decarbonylation step. Finally, ene reaction was applied for the simultaneous formation of cycloheptane d -ring and tetrasubstituted double bond between rings B and C. [ABSTRACT FROM AUTHOR]

Gold‐catalyzed intermolecular reaction leading to dihydronaphthalene derivatives in one pot from two equivalents of ynones with respect to styrene is uncovered. The [4+2] Diels–Alder cycloaddition of ynones and styrenes is catalyzed by a mono‐gold(I) complex and the conjugated acid to provide an unstable 3,8a‐dihydronaphthalene to subsequently undergo an intermolecular ene‐type reaction with the π‐activated ynone to afford multi‐component coupling dihydronaphthalene products. Linear relationships between chiral ligand‐gold complexes and chiral dihydronaphthalene products proves mono‐gold catalysis that triggers an asymmetric tandem Diels–Alder and ene reaction sequence. [ABSTRACT FROM AUTHOR]

Asymmetric access to α-hydroxy-1,4-diketones has been achieved by direct ene coupling of silyl enol ethers with glyoxal electrophiles, mediated by a chiral N , N ′-dioxide–nickel(II) complex catalyst. Successful union of a polyketide silyl enol ether with an α-quaternary glyoxal, generated by dioxirane oxidation of an α-diazo ketone, models a proposed C5 –C6 disconnection of the polyketide and spirocyclic imine domains of the marine natural product, portimine. [ABSTRACT FROM AUTHOR]

[Display omitted] Diels–Alder adducts of levoglucosenone with isoprene, butadiene and piperylene in the presence of AlCl 3 smoothly react with acetaldehyde or benzaldehyde to give products of the ene reaction, the hydroxy group of the primary intermediates participating in the formation of semiketal moiety. The yields of the reaction products depend both on the Lewis acid used (AlCl , BF ·Et O, ZnBr , SnCl or EtAlCl 2) and on the nature of the substrate. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The trifluoropyruvate-ene product without (dehydro)lactone and lactam motifs exhibits remarkably high antagonist activity for human osteocalcin. Abstract The highly stereoselective trifluoropyruvate-ene reaction with steroidal 1,1-disubstituted Δ 20(22) -side chain olefin was achieved by the dicationic BINAP-Pd complex as an effective chiral Lewis acid catalyst to give the Δ 20(21) -steroidal ene-product in high yield and enantioselectivity. The ene product itself without (dehydro)lactone and lactam structures exhibited remarkably high antagonist activity for human osteocalcin even in low binding affinity for human vitamin D hormone receptor. [ABSTRACT FROM AUTHOR]

As a first non‐metal‐catalyzed oxidation for the in situ generation of acylnitroso species, we describe the hypoiodite catalysis using tetra‐n‐butylammonium iodide as precatalyst with tert‐butyl hydroperoxide or hydrogen peroxide as a terminal oxidant. This method can be applied to hetero Diels–Alder (HDA) reactions with dienes and ene reactions with alkenes. Furthermore, the conversions of the representative HDA adduct to nitrone and 2‐amino alcohols were demonstrated. Compared with previous metal‐catalyzed oxidation methods, this work provides a more efficient and environmentally friendly procedure. First example of hypoiodite‐catalyzed oxidation for the in situ generation of acylnitroso species, which can be used in hetero Diels–Alder reactions with dienes and in ene reactions with alkenes. [ABSTRACT FROM AUTHOR]

This is a full account of our studies into the generation of highly functionalised 2-aryl-1,2-dihydropyridines and 2-methylene-3- aryl-1,2,3,4-tetrahydropyridines via intermolecular aryne ene reactions of Hantzsch esters. Furthermore, exposure to excess aryne revealed unusual 3'-aryl-spiro[benzocyclobutene-1,1'-(3',4'-dihydropyridines)]. Mechanistic insights are provided by deuterium-labelling studies and DFT calculations, whilst preliminary cytotoxicity investigations reveal that the spirocycles are selective against colon carcinomas over ovarian cancer cell lines and that all the compounds have high selectivity indices with regards to non-cancer cells. [ABSTRACT FROM AUTHOR]