Studies on the reactions of fluoroalkanesulfonyl azide with aromatic compounds

The thermal decomposition reactions of fluoroalkanesulfonyl azides R_fSO₂N₃ (1) in the presence of various substituted benzene X_nC₆H_6−n [X: CH₃ (n=1, 2, 4, 6), OCH₃ (n=1, 2), C₆H₅CH₂ (n=1), F, Cl, Br] were studied in detail. The N-aryl fluoroalkanesulfonyl amides [R_fSO₂NHC₆H_5−nX_n] were produced as the major products. The ortho/para ratio resembled that of an electrophilic aromatic substituted reaction. An ionic π- or σ-complex was postulated as the intermediate for these reactions.     

Sulfur-mediated radical cyclisation reactions on solid support

Two methods for effecting radical cyclisation reactions of solid-supported 1,6-dienes are described. Additions of thiophenol and p-tolyl benzeneselenosulfonate have each been achieved with a concomitant 5-exo-trig radical cyclisation leading to the formation of highly functionalised cyclopentanes.     

Radical cyclisation reactions with indoles

Several radical cyclisation reactions involving indoles are described. Most notably, we have shown that radical additions to C3 of an indole are frequently facile. A dichotomy in the course of radical cyclisation reactions to C2 of the indole has also been exposed wherein 6-endo-trig cyclisations are propagated by the loss of a hydrogen atom from C2 while 5-exo-trig cyclisations are propagated by hydrogen atom abstraction at C3 from tributyltin hydride. Cyclisations involving the addition of indolyl radical intermediates to arenes have also been demonstrated.     

Keto-alkyne cyclisation reactions: heterocyclic prostacyclin analogues

Simple furan, thiophene and pyrrole analogues of prostacyclin have been prepared from readily-available 4-alkvnyl ketones; the cyclohexa[b]-furano-prostacyclin analogue $\text{3}$ has also been synthesised using the keto-alkyne cyclisation procedure.     

A study into asymmetric Nicholas cyclisation reactions

Three systematic approaches have been employed to investigate asymmetric Nicholas reactions. We found that the use of a chiral N-enoyl derivative provided acceptable levels of selectivity for an intermolecular Nicholas reaction, however, we were unable to identify an auxiliary that could be utilized in an asymmetric conjugate addition and a tandem inter/intramolecular series of Nicholas reactions. The use of chiral pool non-racemic propargyl alcohols, derived from citronellal, provided enhanced levels of selectivity. As a result of these studies we developed a series of Nicholas cyclisations derived from chiral non-racemic salicylaldehyde derivatives. These underwent an extremely rapid and highly efficient cyclisation, under Nicholas conditions, to afford a range of benzopyrans. The adjacent stereogenic centres appear to be formed with high levels of stereocontrol.     

Stereodivergent radical cyclisation reactions of cyclohexa-1,4-dienes

Derivatives of cyclohexa-1,4-diene diol 5 undergo highly diastereoselective free-radical cyclisation reactions. Selective reaction of either double bond is possible depending on the protecting groups used.     

Gas-phase generation and cyclisation reactions of imidoyl radicals

Some 1,2-diarylimidoyl radicals were generated in the gas-phase by intramolecular radical translocation from ortho-imino-aryloxyl radicals, in turn generated under flash vacuum pyrolysis (FVP) conditions. The imidoyls reacted with XR ortho'-substituents in the N-aryl group to give (in most cases) modest yields of cyclisation products. Depending on the nature of the bridging atom (X), the formation of these products was initiated either by a further hydrogen atom translocation (X = CH(2)), or by ipso-attack onto the aryl group (R = Ph), or by direct substitution at the heteroatom (X = S). With XR = N(Me)Ph, the major reaction product was probably the result of a competing pathway not involving the corresponding imidoyl.     

Thermodynamically controlled cyclisation reactions with double phenylsulfanyl migration

Enantiomerically enriched C2-symmetric tetrols were synthesised by a route involving a 'self-metathesis' reaction with Grubbs' second-generation ruthenium catalyst; these tetrols produced interesting bicyclic products when rearranged under acidic conditions.     

Some cyclisation reactions of 2,2′-disubstituted-N-arylpyrroles

Tricyclic products were derived from N-(2-methoxycarbonylphenyl)pyrrole-2-carboxaldehyde ( 2 ) and N-(2-chloromethylphenyl)pyrrole-2-carboxaldehyde ( 8 ).     

The synthesis and reactions of certain pyridazine 1-oxides

Nucleophilic displacement reactions under acidic and basic conditions have been studied with 4,6-dinitro-3-methoxypyridazine 1-oxide ( 1 ) and with 6-chloro-3-methoxy-4-nitropyridazine 1-oxide ( 2 ). Depending on the nature of the nucleophilic reagent and the conditions of the reaction we have found that the chloro group, the nitro group, as well as the methoxy group of 1 and 2 may be displaced by the nucleophile. This type of compound possesses significant in vitro antifungal activity.     

Atom transfer radical cyclisation reactions mediated by copper complexes

This article describes recent advances in the use of copper complexes in mediating atom transfer radical cyclisation reactions (ATRC). Recent developments have included the design of activated complexes which mediate the cyclisation of tri-, di-, and mono-halo derived substrates at ambient temperatures. Using this methodology, cyclisation to give a variety of ring sizes (4-18 membered rings) has been demonstrated. In addition tandem and radical-polar crossover reactions have also been developed. The design of solid supported and perfluorous complexes that mediate cyclisations may make this approach to the synthesis of rings more attractive towards industrial applications.     

Amides as precursors of imidoyl radicals in cyclisation reactions

Amides have been successfully used as precursors of imidoyl radicals for radical cyclisation. The amides have been converted to imidoyl selanides via reaction with phosgene to yield imidoyl chlorides followed by reaction with potassium phenylselanide. Imidoyl selanides were reacted with tributyltin hydride (Bu₃SnH) as the radical mediator with triethylborane or AIBN as initiators to yield imidoyl radicals for cyclisation reactions. Imidoyl radicals have been cyclised onto alkenes to yield 2,3-substituted-indoles and -quinolines and also onto pyrroles and indoles to give bi- and tricyclic heteroarenes.     

Studies on pyridazine derivatives. IV Mesylation reaction of pyridazinylpyrazoles

On mesylation, 1-pyridazinylpyrazoles ( 1 ), give, depending on the substituents and reaction conditions, O-mesylpyrazoles ( 2 ) and O-mesyl-4-N-mesyl-1,4-dihydro-4-pyridyl-pyrazole derivatives ( 3 ). The structures of these compounds were confirmed by ir and ¹H nmr spectral data.     

Synthesis of substituted dihydrobenzothiopyrans and dihydrobenzopyrans by cation-mediated cyclisation reactions

Treatment with acid of thiosalicylaldehyde- and salicylaldehyde-derived phenyl 3-phenyl-2-propenyl thioethers and ethers possessing latent oxonium ion functionality triggers simple or tandem cyclisation to give substituted dihydrobenzothiopyrans and dihydrobenzopyrans. Some derivatisation reactions of the products are described.     

Pyridazines. LXXXIV. Studies on borohydride reduction of pyridazine compounds

Imidazo[1,2-b]pyridazine, s-triazolo[4,3-b]pyridazine and tetrazolo[1,5-b]pyridazine and some derivatives thereof were reduced with sodium borohydride to give the corresponding 5,6,7,8-tetrahydro derivatives. A mechanism for these reductions is proposed and reduction at the C₇-C₈ bond occurs before the reduction of the C₆? N₅ bond. Substituents at position 7 and/or 8 cause a significant decrease in the extent of reduction or lead to a 5,6-dihydro derivative by competitive attack at the 6 position.     

The syntheses of pyridazino[1,2-a] pyridazine derivatives of furan,pyridazine and pyrrole by diels-alder reactions

Diels-Alder adducts were formed in the lead tetraacetate oxidations of substituted cyclic hydrazides of furan, pyridazine and pyrrole dicarboxylic acids in the presence of 1,3-cyclo-hexadiene or 1,3-cyclopentadiene. The products resulting were furo[3,4-g]pyridazino[1,2-a]-pyridazine-6,10-diones, pyridazino[4,5-g]pyridazino[1,2-a]pyridazine-6,11-diones, and pyrrolo-[3,4-g]pyridazino[1,2-a]pyridazine-6,10-diones, respectively. Some hydrogenations and ring opening reactions were studied.     

New indium-mediated cyclisation reactions of tethered haloenynes in aqueous solvent systems

The intramolecular cyclisation of tethered allyl bromides onto terminal alkynes mediated by metallic indium proceeds smoothly and cleanly in mixtures of THF and H₂O to give unsaturated carbocycles and heterocycles in good yield. Alternatively, the cyclisation may be carried out in anhydrous THF with the aid of acid catalysis. The reaction is also mediated by a range of indium salts and proceeds with substoichiometric quantities of indium in the presence of a co-reductant. Deuteration studies show that the reaction proceeds via a concerted syn carboindination of the carbon-carbon triple bond to give an intermediate, which is protonated in situ.     

Intramolecular reactions of 2-indolylacyl radicals: cyclisation upon aromatic rings

The generation of 2-indolylacyl radicals from the corresponding selenoesters under reductive (tributyltin hydride-AIBN) and nonreductive (hexabutylditin, 300 W) conditions and their behaviour in cyclisation reactions upon benzene rings attached either to the indole nitrogen or the C-3 ring position have been studied.