Giovanni Melloni

REDUCTIVE ELECTROPHILIC SUBSTITUTION OF PHTHALANS AND RING EXPANSION TO ISOCHROMAN DERIVATIVES

Reductive cleavage of phthalun, 1a, with Li metal in the presence of a catalytic amount of naphthalene leads to the formation of a stable aromatic dilithium compound. The adducts of the latter with CO2, aldehydes or ketones undergo ring closure to isochroman derivatives, leading to ring expansion of the original heterocycle. The reductive electrophilic substitution procedure was successfully extended to the substituted phthalans 1b and 1c, to afford the corresponding isochroman-3ones in satisfactory yields.

1,2-Bis(phenylsulfonyl)alkenes as versatile groups in organic synthesis: the preparation of alkyl- and aryl-substituted norbornadienes via the Diels-Alder cycloaddition-Grignard reaction-desulfonylation sequence

Abstract A synthetic methodology for the preparation of the formal Diels-Alder cycloadducts of alkyl- and aryl-substituted acetylenes which exemplifies the utility of bis(phenylsulfonyl)alkenes 1 in organic synthesis is presented. The procedure entails [4+2]-cycloaddition of ( E )-1,2-bis(phenylsulfonyl)-1-chloroethylene ( 4 ), Grignard reaction and desulfonylation; each step occurs in high yield.

Electrochemical reduction of activated carbon–carbon double bonds. Part 2. Mechanism and stereochemistry of the reduction of self-protonating indenes

The reduction at a mercury electrode in dimethylformamide of five variously substituted indenes bearing at least one (acidic) hydrogen at C(1) was carried out, under self-protonation conditions and in the presence of phenol as a proton donor. Reduction occurred exclusively at the C(2)–C(3) double bond of the five-membered ring and afforded the corresponding indans of various configurations, with a marked predominance of the cis isomer, under kinetic control. The stoicheiometry was in agreement with a two-electron, two-proton reduction process involving all indene in the case of the presence of phenol or 1/3 indene under self-protonation conditions, the remaining 2/3 acting as a proton donor. Under both conditions direct protonation of the radical anion rather than the dianion formed by disproportionation was observed. Voltammetric and kinetic behaviour of the indenes was found to be dependent on the structure of the substrates, with differences in rate constants of 3–4 orders of magnitude; the balance between the acidity of the indene and the basicity of the corresponding radical anions was discussed. The stereochemistry observed was rationalised in terms of steric effects on the direction(s) of protonation of the intermediates.

Regioselectivity in the reductive cleavage of pyrogallol derivatives: reductive electrophilic substitution of acetals of 2,3-dimethoxyphenol

Acetals of 2,3-dimethoxyphenol were used as the starting materials for the transformation of 1,2,3-trioxygenated benzenes into various 1-oxygenated-2,3-dicarbon-substituted benzenes, via regioselective reductive electrophilic substitution of the 2-methoxy group, followed by conversion into the corresponding triflates and a Pd-catalysed cross-coupling reaction. The regioselectivity of the reductive cleavage is ascribed to twisting of the leaving methoxy group out of the plane of the aromatic ring by the two ortho substituents. According to this methodology, a new synthesis of lunularic acid is presented.

Reactivity of unsaturated substrates under reductive electron transfer conditions. Part 1. Reduction of 1,2,3-triphenyl-1H-indene with sodium metal in various solvents

The reduction of 1,2,3-triphenyl-1H-indene 1 with sodium metal in various solvents was carried out in order to compare the results with those previously obtained in the electrochemical reduction of 1(Hg cathode, dimethylformamide, Bu4N+ ClO4– as supporting electrolyte). The most general reaction observed was reduction of the double bond of the pentatomic cycle to afford the corresponding indanes of different configurations. In two cases (1,2-dimethoxyethane, dioxane) this reaction was accompanied by reduction of the C(1 )–H bond of 1 with formation of the corresponding anion and hydrogen. No rearrangement or cleavage of groups was observed. In a protic solvent (pentan-1-ol) the results are consistent with a reduction process occurring via protonation of the radical anion of 1, affording quantitatively the isomeric indanes with a slight preference for those of cis-configuration around the C(2)–C(3) bond. In liquid ammonia, in contrast, the results are indicative of a reduction process occurring via protonation of dianionic species, leading to the almost exclusive formation of indanes of trans-configuration around the C(2)–C(3) bond. The self-protonation reaction, which is the characteristic process of reduction of 1 under electrochemical conditions in the absence of specific proton donors, was found to be followed only in the case of tetrahydrofuran, where a pseudo-unimolecular decay of a paramagnetic species, likely the radical anion of 1, could be followed in an EPR cavity.

Vinyl cations in organic synthesis. Part 2. A novel synthesis of methylene-1H-indenes (benzofulvenes) by cyclisation of phenyl-substituted but-1-en-3-ynes

A series of phenyl-substituted but-1-en-3-ynes has been prepared and their reactivity toward acid catalysed cycloisomerisation investigated. In boiling dichloromethane or 1,2-dibromoethane, in the presence of a catalytic amount of methanesulfonic acid, 1,1,2,4-tetraphenylbutenyne, 1,1,4-triphenylbutenyne, and (Z)-1,2,4-triphenylbutenyne afforded 1-benzylidene-2,3-diphenyl-1H-indene, (E)- and (Z)-1-benzylidene-3-phenyl-1H-indene and (E)- and (Z)-1-benzylidene-2-phenyl-1H-indene, respectively, in fair to good yields. Under the same conditions, (E)-1,2,4-triphenylbutenyne and (E)- and (Z)-1,4-diphenylbutenyne did not afford cyclisation products and were recovered unchanged. The cycloisomerisation reaction is rationalised in terms of formation of vinyl cation intermediates by exclusive protonation at the 4-position of the butenyne chain followed by intramolecular electrophilic attack on a suitably located and orientated phenyl nucleus in the 1-position.

Electrophilic additions to acetylenes. Part VI. Addition of t-butyl chloride and benzyl chloride to alkynes

The zinc chloride catalysed addition of t-butyl and benzyl chloride to some mono- and di-substituted alkynes has been studied. The reactions afforded the 1 : 1 addition products, with predominant formation of the isomers of E-configuration. This suggested the intervention of a stepwise electrophilic addition mechanism, with the formation of α-alkyl-substituted vinyl cations and the subsequent preferential attack of the nucleophilic Cl– from the less hindered side of the intermediates. However, some discrepancy in the E : Z ratios of the addition products and comparison with analogous stereochemical data obtained in the addition of acids to the same substrates suggested that other mechanisms could be involved, though to a small extent. Discussion of the competition among these mechanisms is given.