Search

This concept review describes the recent achievements on the Heyns rearrangement appeared in literature over the last decade and aims to provide the reader with a general overview of the fundamental synthetic advances in this research area. [ABSTRACT FROM AUTHOR]

The potential of aerogels as catalysts for the synthesis of a relevant class of bis-heterocyclic compounds such as bis(indolyl)methanes was investigated. In particular, the studied catalyst was a nanocomposite aerogel based on nanocrystalline nickel ferrite (NiFe2O4) dispersed on amorphous porous silica aerogel obtained by two-step sol–gel synthesis followed by gel drying under supercritical conditions and calcination treatments. It was found that the NiFe2O4/SiO2 aerogel is an active catalyst for the selected reaction, enabling high conversions at room temperature, and it proved to be active for three repeated runs. The catalytic activity can be ascribed to both the textural and acidic features of the silica matrix and of the nanocrystalline ferrite. In addition, ferrite nanocrystals provide functionality for magnetic recovery of the catalyst from the crude mixture, enabling time-effective separation from the reaction environment. Evidence of the retention of species involved in the reaction into the catalyst is also pointed out, likely due to the porosity of the aerogel together with the affinity of some species towards the silica matrix. Our work contributes to the study of aerogels as catalysts for organic reactions by demonstrating their potential as well as limitations for the room-temperature synthesis of bis(indolyl)methanes. [ABSTRACT FROM AUTHOR]

A stereoselective one‐pot double derivatization of cyclobutene‐1‐carboxylic acid via a mild organic base catalyzed amidation/aza‐Michael addition of benzo[d]oxazol‐2(3H)‐ones has been developed. This unprecedented tandem reaction provides access to novel β‐N‐heterocyclic cyclobutane carboximide derivatives with a trans geometry. The carboximide moiety reacts smoothly with nucleophiles, allowing access to diverse derivatives of trans‐β‐N‐heterocyclic cyclobutanecarboxylic acid, including peptidomimetic structures. [ABSTRACT FROM AUTHOR]

A general strategy for the synthesis of 2-substituted cyclobutanone sulfides via a tandem Brønsted acid-catalyzed nucleophile addition/ring contraction/C3-C4 ring expansion reaction sequence has been exploited. The procedure led to a wide panel of four-membered cyclic ketones in good to excellent yields and with broad substrate scope. Mechanistic aspects and kinetic parameters were investigated by quantum chemical DFT calculations, allowing us to rationalize the different reactivity of 2-aryl- and 2-alkyl-substituted 2-hydroxycyclobutanones towards thiol nucleophiles in reactions mediated by sulfonic acids. NMR and in situ Raman techniques were employed to better understand the reaction kinetics and parameters that affect the desired outcome. [ABSTRACT FROM AUTHOR]

A solvent‐free organocatalyzed intermolecular cyclization reaction starting from β‐substituted γ‐hydroxy‐α,β‐unsaturated esters and aryl isothiocyanates proceeds via an aza‐Michael addition to provide previously unknown quaternary oxazolidine‐2‐thione β3‐amino ester analogs. A panel of diversely‐substituted esters was investigated, including β,γ‐disubstituted examples which provided the target molecules with very high cis diastereoselectivity. [ABSTRACT FROM AUTHOR]

A synthetically useful Z‐selective cascade formal thiyl radical addition, 1,3‐double bond isomerization, oxygen trapping reaction, can be promoted by Eosin B under visible light, leading to the construction of 2‐aryl‐ and alkylthio enone derivatives in good yields. An accurate study on the reactivity of different thiols and the screening of the reaction conditions, allowed us to extend this reaction to a large number of substrates, showing a good functional groups tolerance while highlighting the limitations of this procedure. Background experiments and mechanistic studies were also. performed to rationalize this cascade process. The usefulness of this methodology was finally demonstrated via the transformation of a series of α‐sulfanyl‐enone adducts through selected oxidation reactions, stereoselective synthesis of cyclopropyl ketones, indanones, and pyrazole compounds. [ABSTRACT FROM AUTHOR]

A general strategy for the synthesis of indolyl cyclobutanones via a tandem Brønsted acid catalyzed 2-hydroxycyclobutanone activation–indole nucleophilic addition has been exploited. The procedure leads to a wide range of 2- and 3-functionalized indole derivatives in good to high yields with broad substrate scope. [ABSTRACT FROM AUTHOR]

A novel Brønsted acid promoted condensation reaction between a primary aniline and 2-hydroxycyclobutanone provides access to diverse tryptamine derivatives in moderate to good yields. The proposed mechanism involves an α-iminol rearrangement, ring expansion, ring closure, and a depart-and-return rearrangement process. [ABSTRACT FROM AUTHOR]

We have developed one‐step protocols for the preparation of a large selection of α‐aminocyclopropyl ketones or benzo[d]imidazoles, by reacting 2‐substituted‐2‐hydroxycyclobutanones with aryl amines or o‐phenylenediamines, respectively. In most case the reactions proceed at room temperature and are catalyst‐free. The formation of benzo[d]imidazoles is rationalized in terms of an unusual ring‐closure/ring‐fission process followed by aromatization. [ABSTRACT FROM AUTHOR]

The investigation of the structure of a series of I-O bonded bis(acyloxy)iodoarenes and benzoiodoxolones in chloroform solution, which was carried out by using [super 17]O NMR spectroscopy and density functional theory (DFT) calculations is presented.

A new Brønsted acid catalysed solvent‐free cascade reaction consisting of a ring closure‐ring fission process between α‐arylaminocyclobutanones and alcohols has been established, providing highly functionalised 3‐(2‐alkoxyethyl)indoles in good to excellent yields. [ABSTRACT FROM AUTHOR]

A general strategy for the synthesis of arylthio cyclopropyl carbaldehydes and ketones via a Brønsted acid catalyzed arylthiol addition/ring contraction reaction sequence has been exploited. The procedure led to a wide panel of cyclopropyl carbaldehydes in generally high yields and with broad substrate scope. Mechanistic aspects and synthetic applications of this procedure were investigated. [ABSTRACT FROM AUTHOR]

We describe a photochemical reaction using two starting materials, a cyclopent-2-enone and an alkene, which are transformed in a controlled manner via the initial [2+2]- photocycloaddition adducts into cyclobutene aldehydes (conveniently trapped as stable acetals) or unprecedented angular tricyclic 4:4:4 oxetane-containing skeletons. These compounds are formed through tandem or triple cascade photochemical reaction processes, respectively. Small libraries of each compound class were prepared, thus suggesting that this photochemistry approach opens new opportunities for synthesis design and for widening molecular diversity. [ABSTRACT FROM AUTHOR]

The Paternò-Büchi reaction between benzaldehyde and trimethylsilyloxycyclopentene gave access to an unprecedented silyl ether derivative of 6-oxabicyclo[3.2.0]heptan-1-ol. The bicyclic structure underwent selective reductive ring opening and acid-catalyzed pinacol-type rearrangement reactions with complete regioselectivity, accompanied by moderate to excellent mechanism-dependent diastereoselectivity. [ABSTRACT FROM AUTHOR]

An original synthetic protocol has been developed for the preparation of highly functionalized tryptamines from 2-hydroxycyclobutanone and secondary arylamines via a solvent-free Brønsted acid catalysed two-step reaction sequence. [ABSTRACT FROM AUTHOR]

An organocatalytic enantioselective synthesis of α-(benzylamino)cyclobutanones has been achieved by employing a tandem condensation/intramolecular rearrangement/proton transfer reaction and starting from racemic α-hydroxycyclobutanone and a selection of benzylamines. This reaction sequence afforded the products in good to high yields with moderate to high enantioselectivities. [ABSTRACT FROM AUTHOR]

The organocatalytic synthesis of new α-acyloxy-3-arylpropionic thioesters has been accomplished providing some enantioenriched important aryllactic acid derivatives in good yield and enantioselectivities. [ABSTRACT FROM AUTHOR]

A variety of enantiomerically enriched tetrahydrofuran spirocyclic derivatives have been synthesised by a sequential enantioselective proline-induced stereospecific resolution through aldol reaction of ( E/ Z)-(phenylsulfanyl)cycloalkanecarbaldehydes followed by a ketone reduction, acid-catalysed [1,2]-SPh stereospecific migration, and ring-closure reaction. [ABSTRACT FROM AUTHOR]

The oxidation of organosulphides catalysed by hydrogen bonding donors derived from aminotetrazole has been studied. The oxidation reaction was performed in a H2O solution using H2O2 as a versatile, green and chemoselective new approach to sulphoxides. Sulphoxide compounds are obtained in high yields and excellent selectivity through a new and easy to perform oxidation protocol. Aminotetrazole derivatives can be recycled by filtration and reused several times without expensive purification procedures. [ABSTRACT FROM AUTHOR]

A practical method for the synthesis of optically active α-amino cyclobutanones has been developed, via an organocatalytic asymmetric condensation reaction between racemic 2-hydroxycyclobutanone and chiral N-alkyl-α-amino acid ester derivatives. [ABSTRACT FROM AUTHOR]

BACKGROUND The gypsy moth Lymantria dispar L. is a widespread pest that causes economic damage to cork oak forests. Females produce the sex pheromone (+)-(7 R,8 S)-epoxy-2-methyloctadecane, known as (+)-disparlure [(+)D], for long-distance attraction of conspecific males. A (+)D analogue, 2-decyl-1-oxaspiro[2.2]pentane ( OXP-01), neither stimulating nor attractive by itself, causes short-time inhibition of male response in a 1:1 blend with (+)D. The authors investigated whether and how the biological activity of the natural pheromone is affected by OXP-01 on a long-time basis (up to 16 days), also by looking at possible physicochemical reciprocal interactions. RESULTS Blending of (+)D with OXP-01 decreased, under low evaporation rate, the pheromone effectiveness, as assessed by electroantennogram recordings. In male trappings, within the first 24 h, OXP-01 decreased and later enhanced the blend attractiveness, but only under high evaporation rate. Gas chromatography-mass spectroscopy indicates that quantitative retrieval of (+)D from blend cartridges is higher than for pure pheromone, and nuclear magnetic resonance measurements show that OXP-01 produces, possibly by Van der Waals interactions, a bimolecular entity with pheromone causing retention and lengthening of its attractiveness over time. CONCLUSION The biological and physicochemical interactions between (+)D and OXP-01 may provide valuable information for the optimisation of pheromone-based control strategies for gypsy moths. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

A catalytic enantioselective synthesis of α-arylaminocyclobutanones from racemic α-hydroxycyclobutanone and a selection of N-alkylanilines has been established, via a tandem condensation/keto-enol tautomerization process reminiscent of the Amadori and Heyns rearrangements. [ABSTRACT FROM AUTHOR]

An overview of the most important synthetic strategies currently available for the preparation of cyclopent-2-enones is presented and illustrated with recent applications. [ABSTRACT FROM AUTHOR]

In the last decade a certain number of new cyclobutane and cyclobutanone synthesis and functionalization protocols have been published. Organo- and biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have been developed with interesting results. Also, successful new total synthesis of bioactive compounds and drugs have been recently reported where a four membered ring represented the key intermediate. Therefore, the rising interest in this field represents a great point of discussion for the scientific community, disclosing the synthetic potential of strained four membered ring carbocyclic compounds. Herein we report a critical survey on the literature concerning the enantiocontrolled synthesis and functionalization of cyclobutane derivatives, with particular attention to metal-free, low impact methodologies, published during the period 2000-2013. [ABSTRACT FROM AUTHOR]

The stereoselective solvent-free organocatalyzed aldol reaction of 2-hydroxycyclobutanone with a selection of aromatic aldehydes has been investigated. Using L-threonine (20 mol%), deracemized aldol adducts featuring a chiral quaternary center were obtained in yields up to 72%, with syn selectivity up to 85:15 and ee up to 84%. The title compound has markedly superior reactivity to other α-hydroxy ketones. [ABSTRACT FROM AUTHOR]

L-Tryptophan has been shown to catalyse the enantioselective aldol reaction between 2-hydroxycyclobutanone and an aromatic aldehyde in DMF solution. The reaction is completely regioselective and gives the 2,2-disubstituted cyclobutanone in up to 80% yield. The major adduct is obtained with ee values up to 67%, and has an anti relative configuration which contrasts with the selectivity of organocatalysed aldol reactions conducted on acyclic hydroxyacetone substrates. [ABSTRACT FROM AUTHOR]

An organocatalyzed enantioselective desymmetrization reaction for converting 3-substituted cyclobutanones into 4-substituted 5-hydroxy-γ-lactams is presented. This involves a ring-expanding O-nitroso aldol-cyclization domino sequence. This synthetic protocol provides access to five-membered ring systems in good yields with the generation of two new stereogenic centers. [ABSTRACT FROM AUTHOR]