Ugo Azzena

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.

Reductive Cleavage of Benzannelated Cyclic Ethers and Amines: Synthetic Applications

Abstract Reduction of symmetrical intramolecular diarylmethyl ethers (3a and 8a) and amines (3b and 8b) with alkali metals in THF allows the generation of unsymmetrical oxy- or amino-functionalised arylmethyl organometallics. Such intermediates were successfully trapped with various electrophiles, allowing a new access to unsymmetrically 2,2′-disubstituted-1,1′-biaryls (5aa–5bf) and 1,8-disubstituted naphthalenes (10aa–10be).

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.

Reductive lithiation of arylalkyl methyl ethers

Abstract We have investigated the reductive cleavage of arylalkyl methyl ethers with an excess of lithium metal and a catalytic amount of naphthalene. The reaction proceeds regioselectively in the presence of various substituents on the aromatic ring, allowing access to a wide array of arylalkyl lithium derivatives, some of which are not easily accessible by conventional methods.

Tuning the Reducing Properties of 1,2-Diaryl-1,2-disodiumethanes

We investigated the reducing properties of a series of 1,2-diaryl-1,2-disodiumethanes by means of equilibration reactions. The electron-donor power of these vic-diorganometals is strongly affected by the nature of substituents present either on the aromatic ring(s) or on the carbanionic centers, and it can be correlated with their ability to delocalize the arylmethyl carbanions. These findings are supported by electrochemical analysis of the reduction behavior of the parent 1,2-diarylalkene. Applications of these results to the reduction of selected substrates are described.

Metalation of arylmethyl alkyl ethers

Abstract Arylmethyl alkyl ethers 1a-11 were metallated with n-BuLi or sec-BuLi in THF at different temperatures, affording α-alkoxy-substituted arylmethyllithium derivatives. At low temperature, the organometallics derived from methyl and isopropyl ethers are sufficiently stable to react with added electrophiles affording the expected products 4aa-4jb. On the contrary, under similar conditions, lithium derivatives of primary alkyl benzyl ethers rapidly decay to benzyl alcohol 3.

Metalation of arylmethyl methyl ethers and connection with their reductive electrophilic substitution

Abstract Stable α-methoxy arylmethyl carbanions can be generated by metalation of arylmethyl methyl ethers, 1 , with n -BuLi in THF at −40 °C, avoiding Wittig rearrangement to the corresponding alkoxides 2 . Reaction of these carbanions with various electrophiles afforded the expected products 3 in satisfactory yields. Connection between the metalation procedure and the reductive electrophilic substitution of arylmethyl methyl ethers allowed the transformation of compounds 1 into 2-arylpropanoic acids, 5 .

Generation and Reactivity of α-Amino-Substituted Arylmethyllithium Organometallics

Abstract Reductive cleavage of open chain and cyclic α- N , N -dialkylamino-substituted benzyl alkyl ethers 1a – f with a dispersion of Li metal and a catalytic amount of naphthalene in THF, allowed easy access to a wide array of α- N , N -dialkylamino-substituted benzyllithium derivatives. Reaction of these organometallics with various electrophiles afforded the expected products in satisfactory yields.

BH3-promoted stereoselective β-lithiation of N-alkyl-2-phenylaziridines.

BH(3) complexes of N-alkyl-2-phenylaziridines have been synthesized and their structure and stereochemistry proved with DFT calculations and NMR experiments. It has been demonstrated that the Lewis acid complexation is able to promote a regioselective β-lithiation in 2-phenylaziridino-borane complexes. The lithiated intermediates were configurationally stable, allowing an enantioselective preparation of cis-2,3-disubstituted aziridines.

Reductive electrophilic substitution of pyrogallol derivatives: Synthesis of 2,3-disubstituted phenols

Abstract 1-2-Dimethoxy-3-methoxymethoxybenzene, 1 , was used as the starting material for the transformation of a 1,2,3-trioxybenzene into various 1-oxy-2,3-dicarbobenzenes, via regioselective reductive electrophilic substitution of the 2-methoxy group followed by Pd-catalyzed cross-coupling reaction.