Ene-type Reaction Research Articles

Copper-catalyzed formation of dihydrothiazoles and functionalization through subsequent ene reactions

Propargyl thioimidates synthesized from readily-available starting materials are cyclized into non-aromatic dihydrothiazoles with high chemoselectivity using copper (I) iodide as a catalyst. These molecules engage in ene-type reactions with aldehyde, imine, and azo reacting partners with concomitant aromatization. A one-pot tandem hydroamination/ene process has been developed.

Peroxidase-induced C-N bond formation via nitroso ene and Diels-Alder reactions.

The formation of new carbon-nitrogen bonds is indisputably one of the most important tasks in synthetic organic chemistry. Here, nitroso compounds offer a highly interesting reactivity that complements traditional amination strategies, allowing for the introduction of nitrogen functionalities via ene-type reactions or Diels-Alder cycloadditions. In this study, we highlight the potential of horseradish peroxidase as biological mediator for the generation of reactive nitroso species under environmentally benign conditions. Exploiting a non-natural peroxidase reactivity, in combination with glucose oxidase as oxygen-activating biocatalyst, aerobic activation of a broad range of N-hydroxycarbamates and hydroxamic acids is achieved. Thus both intra- and intermolecular nitroso-ene as well as nitroso-Diels-Alder reactions are performed with high efficiency. Relying on a commercial and robust enzyme system, the aqueous catalyst solution can be recycled over numerous reaction cycles without significant loss of activity. Overall, this green and scalable C-N bond-forming strategy enables the production of allylic amides and various N-heterocyclic building blocks utilizing only air and glucose as sacrificial reagents.

Cover Feature: Labeling and Characterization of Phenol‐Containing Glycopeptides Using Chemoselective Probes with Isotope Tags (ChemBioChem 14/2021)

Developing new tools to target natural products (NPs) can be applied to isolate novel NPs from complex samples. We have developed native and deuterated chemoselective labeling probes to target phenol-containing glycopeptides by the ene-type reaction. After “clicking” with the biotin handle, the labeled NPs can be enriched, followed by the LC-MS and MSn analysis for structural prediction. Using Amycolatopsis orientalis as an example, a vancomycin-related glycopeptide was labeled and characterized by our labeling strategy, showing its potential in glycopeptide discovery. More information can be found in the Communication by T.-S. A. Wang et al.

A Nazarov-Ene Tandem Reaction for the Stereoselective Construction of Spiro Compounds.

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.

Palladium-Catalyzed Intramolecular Alder-Ene Type Cycloisomerization Reactions.

An overview of the recent literature on palladium-catalyzed intramolecular Alder-ene (IMAE) reaction of a variety of 1,n-unsaturated systems is presented. The reaction which was first reported by Trost and Lautens provided an efficient alternative to the thermal or Lewis acid catalyzed cycloisomerizations involving ene-type reaction. The IMAE cyclization of enynes and dienes has emerged as an important area and found significant applications in building up of complex molecular architectures and in the synthesis of several bioactive natural products. Since highly impactful reviews on this subject have covered the literature till 2015, this article focuses on summarizing the works subsequent to 2015.

Role of Singlet Oxygen in Combustion Initiation of Aromatic Fuels

Application of singlet oxygen in oxy-fuel systems reduces the activation energy of the initiation reactions, accelerating the chain-branching mechanism and decreasing the overall ignition temperature. However, the underlining reaction mechanism of the surface-generated singlet oxygen O2 1Δg that reacts with fuel surrogates (i.e., toluene) in the gas media remains poorly explored. Herein, comprehensive mechanistic and thermo-kinetic accounts underpinning the reaction of the simplest alkylbenzene, namely, toluene, with singlet oxygen in the gas phase are reported. In analogy to reaction of singlet oxygen with benzene, the titled reaction branches into several opening channels. The 1,4 cycloaddition and ene type reactions of toluene with singlet oxygen affords p-quinonemethide (4-methylenecyclohexa-2,5-dienone) and o-quinonemethide (6-methylenecyclohexa-2,4-dienone), respectively (i.e., very reactive intermediates). The initiation of the para channel follows a concerted mechanism through an enthalpic barrier...

Revealing carbocations in highly asynchronous concerted reactions: The ene-type reaction between dithiocarboxylic acids and alkenes

The ene-type reaction between (dithio)carboxylic acids and alkenes has been studied computationally by DFT and topological (analysis of the electron localization function, ELF) methods. The reaction proceeds under kinetic control and the observed differences in regioselectivity are well-explained by the relative stability of the different transition structures. In agreement with experimental observations, electron-rich alkenes lead to Markownikoff adducts while electron-poor alkenes lead to Michael adducts. In all cases the reaction proceeds through an only transition structure (one kinetic step) although a different synchronicity was observed depending on the alkene electronics. The ELF analysis of the reactions corroborates the existence of a transient carbocation (hidden intermediate) in the reactions with electron-rich alkenes. On the other hand, electron-poor alkenes proceed through a more synchronous concerted mechanism. It can be predicted that with electron-rich alkenes bearing highly donating the transient carbocations might be captured by a nucleophile.

Product-oriented chemical surface modification of a levansucrase (SacB) via an ene-type reaction.

Carbohydrate processing enzymes are sophisticated tools of living systems that have evolved to execute specific reactions on sugars. Here we present for the first time the site-selective chemical modification of exposed tyrosine residues in SacB, a levansucrase from Bacillus megaterium (Bm-LS) for enzyme engineering purposes via an ene-type reaction. Bm-LS is unable to sustain the synthesis of high molecular weight (HMW) levan (a fructose polymer) due to protein-oligosaccharide dissociation events occurring at an early stage during polymer elongation. We switched the catalyst from levan-like oligosaccharide synthesis to the efficient production of a HMW fructan polymer through the covalent addition of a flexible chemical side-chain that fluctuates over the central binding cavity of the enzyme preventing premature oligosaccharide disengagement.

Catalytic enantioselective ene-type reactions of vinylogous hydrazone: construction of α-methylene-γ-butyrolactone derivatives.

The catalytic asymmetric ene-type reactions of vinylogous hydrazone were accomplished by using chiral N,N'-dioxide-metal salt complexes as catalysts. A wide range of electrophiles, including isatins, α-ketoester, imines, and aldehydes reacted with (E)-2-methyl-N-(piperidin-1-yl)prop-2-en-1-imine efficiently, affording the corresponding homoallylic alcohols and amines in high yields (up to 99%) with excellent ee values (up to 99%). The methodology provided a convenient way to synthesize bioactive chiral α-methylene-γ-butyrolactone derivatives.

Stereoselective Synthesis of Nitrogen-Containing Compounds from Enamines.

The domino reaction of enamines, electrophiles (N-sulfonylimines, N-tosylisocyanate, or diethyl azodicarboxylate), and trichlorosilane provided trans-amines (trans/cis = > 99:1 to 96:4). Meanwhile, the sequential imino ene-type reaction of enamines and electrophiles/NaBH3CN reduction afforded cis-amines (trans/cis = 1:>99 to 15:85). The reversal of selectivity is discussed on the basis of diastereofacial selection of the plausible iminium ion intermediates. For the domino reaction of cyclic enamines and cyclic imines, high enantioselectivity (er = 95.7:4.3 to 99.9:0.1) was achieved by utilizing chiral Lewis base catalysts.

Reaction of Aniline with Singlet Oxygen (O21Δg).

Dissolved organic matter (DOM) acts as an effective photochemical sensitizer that produces the singlet delta state of molecular oxygen (O21Δg), a powerful oxidizer that removes aniline from aqueous solutions. However, the exact mode of this reaction, the p- to o-iminobenzoquinone ratio, and the selectivity of one over the other remain largely speculative. This contribution resolves these uncertainties. We report, for the first time, a comprehensive mechanistic and kinetic account of the oxidation of aniline with the singlet delta oxygen using B3LYP and M06 functionals in both gas and aqueous phases. Reaction mechanisms have been mapped out at E, H, and G scales. The 1,4-cycloaddition of O21Δg to aniline forms a 1,4-peroxide intermediate (M1), which isomerizes via a closed-shell mechanism to generate a p-iminobenzoquinone molecule. On the other hand, the O21Δg ene-type reaction forms an o-iminobenzoquinone product when the hydroperoxyl bond breaks, splitting hydroxyl from the 1,2-hydroperoxide (M3) moiety. The gas-phase model predicts the formation of both p- and o-iminobenzoquinones. In the latter model, the M1 adduct displays the selectivity of up to 96%. A water-solvation model predicts that M1 decomposes further, forming only p-iminobenzoquinone with a rate constant of k = 1.85 × 109 (L/(mol s)) at T = 313 K. These results corroborate the recent experimental findings of product concentration profile in which p-iminobenzoquinonine represents the only detected product.

ChemInform Abstract: Rhodium Catalyzed Diastereoselective Synthesis of 2,2,3,3‐Tetrasubstituted Indolines from N‐Sulfonyl‐1,2,3‐triazoles and ortho‐Vinylanilines.

An efficient diastereoselective rhodium catalyzed synthesis of indolines possessing two contiguous tetrasubstituted carbon centers has been achieved with good to excellent yields using ortho-vinylanilines and iminocarbenes derived from N-sulfonyl-1,2,3-triazoles. The reaction affords excellent cis-diastereoselectivity through the initial formation of a N-ylide followed by intramolecular trapping with unactivated alkenes via an ene-type reaction with a well-organized transition state, namely intramolecular carbenylative amination of alkenes. The developed transformation was further extended to the successful synthesis of tricyclic compounds, imidazoindolines, through reduction and hypervalent iodine mediated oxidative cyclization.

ChemInform Abstract: Advancements in Catalytic Asymmetric Intermolecular Ene‐Type Reactions

AbstractReview: [56 refs.

Advancements in Catalytic Asymmetric Intermolecular Ene-Type Reactions

Correction to: Advancements in Catalytic Asymmetric Intermolecular Ene-Type ReactionsSynthesis 2014; 46(17): 2241-2257DOI: 10.1055/s-0034-1378528

Visible-light-mediated 1,2-acyl migration: the reaction of secondary enamino ketones with singlet oxygen.

Secondary enaminones were oxidized by photochemically generated singlet oxygen, followed by nucleophilic addition of alcohol and an unexpected 1,2-acyl migration to afford quaternary amino acid derivatives. An ene-type reaction pathway is proposed. It is distinctively different from the typical [2+2] addition of singlet oxygen to a C=C bond pathway.

Imino ene-type reaction of enamines with N-sulfonylimines and application to diastereoselective synthesis of N-sulfonyl-1,3-diamines

Enamines react rapidly with N-sulfonylimines to afford imino ene-type adducts. The reaction proceeds even at −78°C in the presence of acetic acid and shows high diastereoselectivity. Acid hydrolysis of imino ene-type products affords β-amino ketones, and reduction with NaBH3CN furnishes N-sulfonyl-1,3-diamines with high diastereoselectivities. The stereochemistry of these transformations is considered based on transition state models.

Iron-catalyzed ene-type propargylation of diarylethylenes with propargyl alcohols

The diarylalkenyl propargylic complex framework has been found in many natural products and medicinal regents. Herein, we have disclosed an unprecedented FeCl(3) catalyzed ene-type reaction of propargylic alcohols with 1,1-diaryl alkenes which enabled us to furnish a diarylalkenyl propargylic complex framework in moderate to high chemical yields (up to 98%).

トリエチルホウ素と後周期遷移金属の相乗効果を利用した炭素‐炭素結合形成および切断反応

Ni catalyzes homoallylation of aldehydes with 1,3-dienes in the presence of triethylborane to provide bishomoallyl alcohols. Triethylborane serves as reducing agent and Lewis acid to promote the homoallylation via oxanickelacycles. Under similar conditions, Rh catalyzes the reductive coupling reaction of aldehydes and 1,3-dienes to provide homoallyl alcohols while Pd catalyst promotes the ene-type reaction to provide dienyl homoallyl alcohols.Triethylborane also activates allylic alcohols to form π-allylpalladium key intermediates by oxidative addition of Pd(0) toward allylic C-O bonds and achieves amphiphilic allylations. A combination of Pd catalyst and triethylborane effectively promotes 3-hydroxy-4-pentenoic acid to undergo β-decarboxylative C-C bond cleavage reaction via β-vinyloxapalladacyclopentanone to provide conjugated diene and carbon dioxide.

ChemInform Abstract: One‐Pot Synthesis of Chiral Bicyclo[3.3.0]octatrienes (III) Using Diphenylprolinol Silyl Ether‐Mediated Ene‐Type Reaction.

ChemInformVolume 41, Issue 45 Isocyclic Compounds ChemInform Abstract: One-Pot Synthesis of Chiral Bicyclo[3.3.0]octatrienes (III) Using Diphenylprolinol Silyl Ether-Mediated Ene-Type Reaction. Hiroaki Gotoh, Hiroaki Gotoh Dep. Ind. Chem., Fac. Eng., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorHiroshi Ogino, Hiroshi Ogino Dep. Ind. Chem., Fac. Eng., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorHayato Ishikawa, Hayato Ishikawa Dep. Ind. Chem., Fac. Eng., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorYujiro Hayashi, Yujiro Hayashi Dep. Ind. Chem., Fac. Eng., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this author Hiroaki Gotoh, Hiroaki Gotoh Dep. Ind. Chem., Fac. Eng., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorHiroshi Ogino, Hiroshi Ogino Dep. Ind. Chem., Fac. Eng., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorHayato Ishikawa, Hayato Ishikawa Dep. Ind. Chem., Fac. Eng., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorYujiro Hayashi, Yujiro Hayashi Dep. Ind. Chem., Fac. Eng., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this author First published: 14 October 2010 https://doi.org/10.1002/chin.201045054Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume41, Issue45November 9, 2010 RelatedInformation

ChemInform Abstract: Photolysis of Diazo(pentamethyldisilanyl)methyl Ketones in the Presence of Carbonyl Compounds: Trapping of the Acylsilene Intermediates.

UV photolysis of diazo(pentamethyldisilanyl)methyl ketones 1b – d generates acylsilenes (3-oxo-1-sila-1-propenes) 3 as reactive intermediates, which can be trapped by enolizable carbonyl compounds in an ene-type reaction. With non-enolizable carbonyl compounds or ethyl acetate, they undergo a [4 + 2] cycloaddition. In contrast to the photolysis in the absence of these carbonyl compounds, a Wolff rearrangement of 1b – d (or the derived carbenes) to silyl ketenes 5b – d is observed as a competitive reaction.