Electrophilic Rearrangement Research Articles

Vilsmeier-Haack-Initiated Formylative Rearrangement of Spirodioxo-lan-5-ones into Functionalized 4,5,6,7-Tetrahydrobenzofurans.

Pharmaceutically relevant bicyclic furans can be synthesized in a single step from substituted dioxolan-5-ones by reacting with Vilsmeier-Haack reagents. These reagents are generated from POCl3 or PBr3 and DMF. The reaction cascade is mechanistically complex and involves deoxyhalogenation, iminomethylation, and electrophilic rearrangement steps, which are facilitated by the DMF solvent. The synthesis of hard-to-access 4,5,6,7-tetrahydrobenzofurans and substituted aliphatic furans is particularly useful. These compounds are potential isosteres of 2,3-dihydrobenzofuran pharmacophores and could be of interest for drug discovery.

Novel examples of electrophilic rearrangement of substituted pyrimidin-4-ones under Vilsmeier-Haack reaction condition

The critical influence of the size of aliphatic annulated cycles in 2,2-disubstituted pyrimidin-4-ones on the conditions of rearrangement under the action of Vilsmeier-Haack reagent was established. Compounds with a 5-membered ring cycle to pyrimidin-4-one require heating at 1100C for 2 h due to the coplanar arrangement of dimethyliminium and chloriminium groups in intermediates, which leads to placement of a positive charge on the nitrogen atom of the dimethylamino group, which is unfavorable for the reaction. In the case of 6- and 7-membered annulated cycles, there is interatomic repulsion in the intermediates from the hydrogen atoms of methyl and methylene groups, as well as hydrogen atoms of CH and NH, which contributes to placement of a positive charge on the endocyclic atom of nitrogen and chloriminium salt and easier rearrangement. The size of aliphatic annealed and spirocycles to the pyrimidine framework affects not only the reaction conditions but also the formation of products.

Стереоконтролируемые внутримолекулярные превращения (-)-α сантонина

Chemical transformations of eudesmane sesquiterpene γ-lactones, leading to new biologically active compounds, have become an important direction in medicinal chemistry. This article discusses the stereoscopic intramolecular transformations of the sesquiterpene γ-lactone of the eudesmanic structure (-)-α santonin, a perspective natural compound characterized by a wide spectrum of biological activity.Stereoselective synthesis of new practically significant cis-condensed keto-eudesmane esters and ethylated santonin derivatives was carried out at room temperature in an argon atmosphere by the reaction of α-santonin with methyl and ethyl alcohols and alkyl halides in the presence of the Me3CONa-DMF base. It was revealed that, under the reaction conditions, the initial stage of santonin carbanion formation initiates subsequent stages of intramolecular electrophilic rearrangements with the formation of anenolate ion, which futhur interacts stereoselectively with nucleophilic and electrophilic reagents.It was shown that the synthesis of C4-α-ethyl-santonin with a six-membered ring configuration in the form of a distorted chair-chair can serve as a confirmation of the proposed mechanism of formation of practically valuable 6-keto-eudesmane ethers. In this article, the structure and spatial structure of the synthesized compounds is established using modern physicochemical and spectroscopic (1H NMR, 2D COZY NMR, NOESY, mass-spectrometry and X-ray structural analysis) research methods.

Novel rearrangement of substituted spiroimidazolidinones into quinoline derivatives via Vilsmeier-Haack reagent

A novel rearrangement was discovered by reacting 1,4-diazaspiro-[4,5]-decan-2-ones with a Vilsmeier-Haack reagent to give previously unknown aminoquinoline derivatives. The reaction proceeds as an electrophilic rearrangement under mild conditions with a satisfactory yield of reaction products.

Cleavage of the Inert C(sp2)-Ar σ-Bond of Alkenes by a Spatial Constrained Interaction with Phosphinidene.

[1 + 2] cycloaddition is a classical reaction between the electrophilic phosphinidene and an alkene. However, a spatial constraint blocks this well-known reaction and enables an unprecedented chemoselective C(sp2)-Ar σ-bond insertion of the alkene. The theoretical calculations demonstrate that this C-C bond cleavage is energetically feasible and thermodynamically favored through an electrophilic rearrangement and concomitant 1,9-aryl migration without involving any strained intermediate.

Redox-Neutral α-Arylation of Alkyl Nitriles with Aryl Sulfoxides: ARapid Electrophilic Rearrangement.

A facile α-arylation of nitriles has been developed by simply introducing Tf2O and DABCO to the mixture of nitriles and aryl sulfoxides. The transformation consists of two sequential steps: (i) Tf2O-initiated electrophilic assembly and and (ii) DABCO-triggered rearrangement. Each step can be tuned independently by changing the temperature and/or base. This adjustability allows the method to accommodate a wide range of substrates. Notable features of this new protocol include remarkable efficiency (20 min, -30 °C), exclusive regioselectivity, and high functional group compatibility, which can be challenging issues in traditional approaches. NMR studies not only identified a unique, highly unstable sulfonium imine complex but also demonstrated the importance of temperature in the formation and manipulation of this key intermediate. Further DFT calculations suggested that an electrophilic assembly, followed by removal of HOTf (by base), and finally [3,3]-sigmatropic rearrangement are three key stages in the reaction. The versatile transformability of the products and easy scalability of this reaction are also exhibited here.

Investigation of cationic Claisen-type electrophilic rearrangements of amides

Herein we report an extension of the electrophilic rearrangement of amides to the preparation of α-prenyl-hydrocoumarins, indoles, isoquinolines and dihydro-isoquinolinones. An unusual competitive sulfonyl migration, uncovered upon attempted aza-Claisen rearrangement, is also described.

Reactivity of Substituted 2-Spiropyrimidin-4-Ones Under Vilsmeier–Haack Conditions

Substituted 2-spiropyrimidin-4-ones are formylated at room temperature under the conditions of the Vilsmeier–Haack reaction. When cautiously heated they undergo electrophilic rearrangement.

Synthesis and Formylation of Substituted 2-Spiropyrimidin-4-ones and Related Compounds

Treatment of cyclohexanone-2-carboxamide with cyclic ketones provides oxazine derivatives while refluxing in toluene with ammonium acetate and cyclic ketones yields substituted 2-spiropyrimidin-4-ones. Depending on the ratio of reactants, the oxazines and substituted 2-spiropyrimidin-4-ones under Vilsmeier-Haack conditions undergo formylation or an electrophilic rearrangement.

Electrophilic Rearrangements of Chiral Amides: A Traceless Asymmetric α-Allylation

A one-pot protocol for the asymmetric α-allylation reaction is reported relying on a key efficient asymmetric Claisen rearrangement, triggered by electrophilic activation of chiral pseudoephedrine amides. Subsequent reduction or hydrolysis of the resulting iminium ions provides highly enantioenriched α-allylic aldehydes or carboxylic acids in a traceless manner. Compared to traditional alternatives which make use of strongly basic conditions, the work presented herein displays unprecedented functional group tolerance.

SYNTHESIS AND FORMYLATION OF SUBSTITUTED 2-SPIROPYRIMIDIN-4-ONES AND RELATED COMPOUNDS

Treatment of cyclohexanone-2-carboxamide with cyclic ketones provides oxazine derivatives while refluxing in toluene with ammonium acetate and cyclic ketones yields substituted 2-spiropyrimidin-4-ones. Depending on the ratio of reactants, the oxazines and substituted 2-spiropyrimidin-4-ones under Vilsmeier-Haack conditions undergo formylation or an electrophilic rearrangement. Authors: V. I. Markov, O. K. Farat, S. A. Varenichenko, E. V. Velikaya, R. I. Zubatyuk, and O. V. Shishkin. English Translation in Chemistry of Heterocyclic Compounds , 2013, 49 (8), pp 1158-1165 http://link.springer.com/article/10.1007/s10593-013-1358-2

ChemInform Abstract: BF3‐Promoted Synthesis of Spiroindenyl Heterocycles.

AbstractKey step is a novel cascade intramolecular electrophilic rearrangement of crude tertiary diaryl alcohols, which are prepared from esters (I), (IV) or (VII) with arylmagnesium bromides.

ChemInform Abstract: Electrophilic 1,3-C→N- and -N→C- Migrations in Saturated Systems

A new type of intramolecular electrophilic rearrangements involving the shift of COOAlk groups from carbon to an N-anionic center is considered. Carbanionic species with COOAlk groups at anionic centers containing no acidic hydrogen react unusually with alkyl(aryl) iso(thio)cyanates giving carbamates as a result of insertion of RNCX into the C−C bond. The kinetics and mechanism of insertion of aryl isocyanates into the C−C bond of the phosphonium zwitterion obtained from triisopropylphosphine and ethyl 2-cyanoacrylate are discussed. The reaction of α-carbanions derived fromN,N-disubstituted amides with methyl trifluoromethanesulfonate results inO-methylation. Some possibilities of back N→C− migrations are considered.

ChemInform Abstract: Unexpected Electrophilic Rearrangements of Amides: A Stereoselective Entry to Challenging Substituted Lactones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Unexpected Electrophilic Rearrangements of Amides: A Stereoselective Entry to Challenging Substituted Lactones

Unexpected Electrophilic Rearrangements of Amides: A Stereoselective Entry to Challenging Substituted Lactones

Internal Alkyne-to-vinylidene Isomerization at Cationic Ruthenium and Iron Complexes

Abstract Cationic ruthenium and iron complexes [CpM(PP)]+ (Cp = η5-C5H5; M = Ru and Fe; PP = Ph2PCH2CH2PPh2, 2PPh3) can affect vinylidene rearrangement of general internal alkynes via the 1,2-migration of aryl and alkyl groups. Judging from the migratory aptitude of substituted aryl groups, the present reaction is viewed as an uncommon electrophilic rearrangement.

Formation of Vinylidenes from Internal Alkynes at a Cyclotriphosphato Ruthenium Complex

A ruthenium cyclotriphosphato (P(3)O(9)(3-)) complex with a labile MeOH ligand can affect the vinylidene rearrangement of general internal alkynes via the 1,2-migration of alkyl, aryl, and acyl groups. This provides the first internal alkyne-to-vinylidene isomerization with high generality. Several intermediary eta(2)-alkyne complexes could be isolated and were successfully transformed into the corresponding vinylidene complexes. The reaction mechanism is also discussed on the basis of a kinetic study and migratory aptitude of alkyl, aryl, and acyl groups; the present reaction proceeds via an intramolecular process and is viewed as an uncommon electrophilic rearrangement.

Regioselective Electrophilic Aromatic Substitution Reactions over Reusable Zeolites

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Regioselective Electrophilic Aromatic Substitution Reactions over Reusable Zeolites

Zeolite catalysts can play an important role in the development of greener organic syntheses through their abilities to act as heterogeneous catalysts, support reagents, entrain by-products, avoid aqueous work-ups and enhance product selectivities via shape-selectivity. We have shown that zeolites under modest conditions can have advantages in para-regioselective nitration, alkylation, acylation, methanesulfonylation and halogenation of aromatic compounds. They can also assist in the electrophilic rearrangement of aryloxiranes. The zeolites can be easily removed from reaction mixtures by filtration and regenerated by heating and can then be reused several times to give the same selectivity.

Asymmetry by Electrophilic Rearrangement of Symmetric 2-Pyridone Photodimers

[reaction: see text] Halogenation of achiral trans-2-pyridone photodimers results in 1,3-migration of an amide nitrogen and formation of a chiral structure with six stereogenic centers and well-differentiated functionality. The reactivity of this product toward nucleophiles, including the allylic halide, is dominated by participation by the amide nitrogen.