Preparation of the conjugated polyene chains with the 1,4-dimethyl substitution

Allylic sulfones undergo the conjugate addition to diethyl chloroisopropylidenemalonate, followed by intramolecular cyclopropanation. DBU-promoted ring opening and subsequent desulfonation reactions of the resulting adduct produce the conjugated polyene chains with the 1,4-dimethyl substitution.     

Ring-fluorinated isoquinoline and quinoline synthesis: intramolecular cyclization of o-cyano- and o-isocyano-beta,beta-difluorostyrenes

o-Cyano-beta,beta-difluorostyrenes react with organolithiums selectively at the cyano carbon to generate the corresponding sp(2) nitrogen anions, which in turn undergo intramolecular replacement of the vinylic fluorine to afford 3-fluoroisoquinolines. Similarly, the reaction of beta,beta-difluoro-o-isocyanostyrenes with organomagnesiums or -lithiums generates the corresponding sp(2) carbanions on the isocyano carbon. Subsequent cyclization via substitution of the fluorine leads to 3-fluoroquinolines. [reaction: see text]     

Synthesis of substituted tetrahydrofurans via intermolecular reactions of γ-chlorocarbanions of 3-substituted 3-chloro-propylphenyl sulfones with aldehydes

Carbanions of 3-substituted-3-chloropropyl phenyl sulfones add to carbonyl groups of aldehydes to produce aldol type adducts that undergo 1,5-intramolecular substitution giving 2,3,5-trisubstituted tetrahydrofurans. The effect of substituents in the 3-position of these sulfones on the relative rates of 1,3-intramolecular substitution of the corresponding γ-chlorocarbanions and their intramolecular addition are disclosed.     

Hydrogen/deuterium exchange in gas phase reactions of anions with some alkyl phenyl ethers

The gas phase reactions of anions with methyl and ethyl phenyl ether have been studied by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. ¹⁸O-Labelling has shown that part of the reactions of OH^- with methyl phenyl ether proceed via ipso-substitution, the main reaction channel being S_N2 substitution. Deuterium labelling has shown that extensive inter- and intramolecular hydrogen/deuterium exchange can precede the final substitution reaction. Hydrogen atoms originating from the methoxy substituent are involved in this exchange process. The reactions of anions with ethyl phenyl ether proceed mainly via an elimination mechanism. Deuterium labelling has shown that in some cases hydrogen/deuterium exchange takes place prior to elimination.     

Intramolecular cyclopropanation of unsaturated terminal aziridines

[STRUCTURE: SEE TEXT] Regio- and stereoselective deprotonation of bishomoallylic terminal N-Bus (Bus=tert-butylsulfonyl)-protected aziridines generate aziridinyl anions that undergo diastereoselective intramolecular cyclopropanation giving trans-2-aminobicyclo[3.1.0]hexanes in good to excellent yields.     

Reactions of γ-acyloxy-β-ketophosphonates: New routes to 3(2h)- and 2(3h)-dihydrofuranones

Depending on the reaction conditions, γ-acyloxy-β-ketophosphonate anions can undergo either an intramolecular Wittig-like condensation or an unexpected rearrangement which affords an enol ester product.     

Competition between vinylic substitution and conjugate addition in the reactions of vinyl selenoxides and vinyl selenones with nucleophiles in DMF

Vinyl selenoxides and vinyl selenones present a different reactivity towards thiolate or alkoxide anions in DMF. In the case of selenoxides the addition of the nucleophiles regioselectively occurs at the α-carbon leading to the formation of the vinylic substitution products with complete retention of configuration. These reactions occur under very mild conditions indicating that the seleninyl group markedly enhances nucleophilic vinylic substitution rates. The results obtained with vinyl selenones are consistent with competitive nucleophilic attack at the α- and at the β-carbon. The former yields irreversibly the vinylic substitution products, whereas attack at the β-carbon leads to the reversible formation of selenonyl stabilized carbanions. The fate of these intermediates depends upon the nucleophilic reagent employed. With thiolate anions the vinyl selenones are rapidly subtracted from the equilibrium and the carbanion does not give any other product. With methoxide anions, on the contrary, the vinylic substitution is a slow process and the carbanion can give rise to conjugate addition products also. Malonate anions react only at the β-carbon of vinyl selenones and the resulting carbanions suffer proton transfer and intramolecular displacement of the selenonyl group to afford cyclopropane derivatives.     

Regiocontrolled synthesis of the trimeric quinone framework of conocurvone

[reaction: see text] The trimeric quinone framework of conocurvone is crucial for its potent anti-HIV activity. A new synthesis of trimeric quinones based on stepwise substitution of the halogens in 2,3-dihaloquinones by hydroxyquinone anions is described. Chlorinated biquinones are key intermediates that undergo regiospecific substitution reactions to yield trimeric quinone monomethyl ethers.     

Synthesis of cyclopropanes via iodine-magnesium exchange between 3-iodomethyl-1-oxacyclopentanes and organomagnesium reagents

Iodine-magnesium exchange occurs upon treatment of 3-iodomethyl-1-oxacyclopentanes with alkyl Grignard reagents or trialkylmagnesate. The resulting organomagnesium compounds undergo intramolecular nucleophilic substitution in ether to afford cyclopropane skeletons in a stereoselective manner.     

A new synthesis of highly functionalized 2H-pyran derivatives

Ethyl oxo-(2-oxo-cycloalkyl)-ethanoates undergo a smooth reaction with triphenylphosphine and dialkyl acetylenedicarboxylates via intramolecular Wittig reaction to produce spiro-cyclobutene derivatives. These spiro systems undergo electrocyclic ring opening reaction to produce electron-deficient 1,3-dienes, which spontaneously cyclize to 2H-pyran derivatives.     

An unusual substitution reaction directed by an intramolecular re-arrangement

Secondary amines and thiols undertake a substitution reaction on the side chain of 2-bromoethyl-pyridinium derivatives ‘directed’ by an intramolecular re-arrangement. Experimental investigations strongly indicate that the reaction is initiated by an alpha addition of the nucleophile onto the iminium moiety of the N-heteroaromatic cation, followed by a cyclisation and an oxidative ring opening. This novel substitution process is able to occur with less reactive nucleophiles that would not undergo conventional substitution with ‘isolated’ bromoethyl moieties.     

Intramolecular electrophilic displacement of acyl by nitro group during attempted synthesis of 3-nitrocoumarins

2-Hydroxyacetophenones undergo upon nitration in acetic acid a substitution of the acyl by nitro group followed by an intramolecular 1,3-acyl shift reminescent of a retro-Fries rearrangement to yield phenyl esters.     

Fluorescence sensing of anions based on inhibition of excited-state intramolecular proton transfer

Condensation of 2-(2'-aminophenyl)benzoxazole with p-toluenesulfonyl chloride and phenyl isocyanate yields two new anion sensors (TABO and PUBO), which can undergo excited-state intramolecular proton transfer (ESIPT) upon excitation. For the acid receptor TABO, the ESIPT process can be readily disturbed by basic anions such as F-, CH3COO-, and H2PO4- by deprotonating the sulfonamide unit, whereas in the case of PUBO, a good hydrogen-bonding donor, the ESIPT process is inhibited either by the fluoride-induced deprotonation of the urea unit or by the formation of a strong CH3COO--urea intermolecular hydrogen bond complex, and these two types of inhibition mechanisms consequently result in different ratiometric responses. But other anions with less hydrogen-bonding acceptor abilities cannot inhibit the ESIPT. Interestingly, the different inhibition abilities of F-, CH3COO-, and H2PO4- produce different spectral behaviors in PUBO, so this new sensor successfully distinguishes the subtle difference in these three anionic substrates of similar basicity and surface charge density.     

On assistance in β-elimination reactions

It has been shown that organomercury compounds containing strongly electro-negative groups in the β-position and which are not capable of inter- and intramolecular interaction with the mercury atom, undergo symmetrization and substitution reactions rather than β-elimination in the presence of nucleophiles.     

Intramolecular cyclization of acyl radicals onto the azido group: a new radical approach to cyclized lactams

[reaction: see text] Aryl- and alkyl-derived azidoacyl radicals, generated from thiolesters by intramolecular homolytic substitution at the sulfur, can undergo five- and six-membered cyclization onto the azido moiety to give cyclized lactams.     

Vinyl diazophosphonates as precursors to quaternary substituted indolines and cyclopentenes

Vinyl diazophosphonates can be stereoselectively synthesized and, depending upon their substitution pattern, undergo intramolecular C-H insertion reactions or sulfonium ylide rearrangements when exposed to Rh(2)(OAc)(4).     

Cyclization of lithiated pyridine and quinoline carboxamides: synthesis of partially saturated pyrrolopyridines and spirocyclic beta-lactams

Lithiation of N-benzyl pyridine and quinoline carboxamides alpha to nitrogen gives anions that undergo intramolecular attack on the pyridine or quinoline ring, either directly or on activation of the ring by N-acylation. The resulting four-, five-, or six-membered-ring-containing compound may be oxidized, protonated, alkylated, or acylated to give a range of polycyclic heterocycles, including pyrrolopyridines, pyrroloquinolines, benzonaphthyridines, and azaspirocyclic beta-lactams. [reaction: see text]     

Intramolecular Allylations of Carbonions

In the general centaxt of examining a variety of organic, reactions which probably proceed via cyclic transition stares, we predicted scme years ago² that the aniens (II) produced by the action of appropriate bases on allylic esters(I) would undergo intramolecular rearrangement to form the iscmeric carboxylate anions (III).     

A facile route to diastereomeric phosphorus ylides. Chemoselective synthesis of dialkyl (E)-2-[1-(2-oxocyclopentylidene)ethyl]-2-butenedioates

2-Acetylcyclopentanone undergoes a smooth reaction with triphenylphosphine and dialkyl acetylenedicarboxylates to produce dialkyl 2-(1-acetyl-2-oxocyclopentyl)-3-(1,1,1-triphenyl-lambda(5)-phosphanylidene)succinates. These compounds undergo intramolecular Wittig reactions in boiling benzene to produce highly strained spirocyclobutene derivatives, which spontaneously undergo ring-opening reactions to produce dialkyl (E)-2-[1-(2-oxocyclopentyliden)ethyl]-2-butenedioates.     

Intramolecular homolytic aromatic substitution of alkyl 2-benzimidazolyl sulfones as a means of entry into alkyl radicals for organic synthesis

The intramolecular radical aromatic substitution of heteroaryl sulfones by tethered aryl radicals has been investigated as a source of alkyl radicals. The 1-(2-iodobenzyl)benzimidazole-2-sulfonyl system was found to be the most effective, while a tetrazole-based system did not undergo the desired radical aromatic substitution at all. Application of the benzimidazole-based system to the generation of alkyl radical and their subsequent use in radical cyclizations was demonstrated.