Robert F. Wilkins

THE GENERATION OF IMINIUM IONS USING CHLOROSILANES AND THEIR REACTIONS WITH ELECTRON RICH AROMATIC HETEROCYCLES

Abstract Dichlorodimethylsilane and trichloromethylsilane have been used to generate iminium ions from aminals and aminol ethers derived from secondary alkylamines, including glycine derivatives, in aprotic media which were shown to undergo reactions with electron rich aromatic heterocycles, including furan, to give mono-aminoalkylation products in good yields. Whereas chlorotrimethylsilane has been shown to generate iminium ions from aminol ethers, no evidence was adduced for the involvement of iminium ions using aminals. 2,5-Disubstitution of N-methylpyrrole was the major result in reactions of N-methylpyrrole with aminals in the presence of chlorotrimethylsilane where no build up of hydrogen chloride occurs and where chlorotrimethylsilane can function catalytically. Experimental results, including the use of bis(trimethylsilyl)acetamide as a proton scavenger, and some relative rate data, are presented that allow possible mechanisms to be evaluated.

Mannich reactions of furan and 2-methylfuran using pre-formed imonium salts

Summary Good yields of 2-dialkylaminomethylfurans are obtained when N , N -dialkylmethylene-imonium chlorides are allowed to interact with furan in acetonitrile at room temperature; similar results are obtained using 2-methylfuran.

Mannich reactions of π-excessive heterocycles using bis-(dialkylamino)methanes and alkoxydialkylaminomethanes activated with acetyl chloride or sulphur dioxide

Abstract Π-Excessive heterocycles react rapidly with bis(dialkylamino)methanes (aminals) and alkoxydialkylaminomethanes (aminol ethers) in acetonitrile to afford Mannich bases in good yields when activated by means of an acidic reagent such as acetyl chloride or sulphur dioxide: the principal compound studied was N -methylpyrrole.

Mannich reactions of nucleophilic aromatic compounds involving aminals and α-amino ethers activated by chlorosilane derivatives; catalysis by chlorotrimethylsilane

Aminals and α-amino ethers afford N,N-dialkylmethyleneammonium salts by reaction with dichloro(dimethyl)- and trichloro(methyl)-silanes, but whereas chlorotrimethylsilane interacts with α-amino ethers to yield iminium salts, the reaction of the latter silane with aminals does not: in situ Mannich reactions may be carried out using these systems, and in the case of the reactions using chlorotrimethylsilane and aminals the reactions can be catalytic with respect to the silane.

A new route to secondary amines from bis-(alkoxymethyl)-alkylamines - the activation of an aminomethyl group and protection of the product by the same functional group☆

Treatment of N,N-bis(alkoxymethyl)alkylamines with a variety of acidic reagents affords good yields of N-alkoxymethyl-N-alkylmethyleneiminium salts which react with trimethylsilyl enol ethers, and nucleophilic aromatic substrates to form protected secondary amines or tertiary amines by domino reactions; silyl ketene acetals afford tertiary amines only.

Mannich reactiohs of aryltrialkylstannunes in aprotic solvents

Abstract Aryltributyl- and aryltrimethyl-stannanes react with a range of N , N -dialkylmethylene-imonium salts to afford N , N -dialkylaminomethyl derivatives in good yields. The method can be used to obtain regloisomers that are not available using classical procedures. “In situ” reactions can also be carried out using alkoxydialkylaminomethanes (aminol ethers) and bis(dialkylamino)methanes (aminals) together with chlorotrimethyl- and trichloromethyl-silanes as the source of the electrophile. However, the “in situ” reactions do not afford good yields in the majority of cases, as a result of the inhibition of imonium salt formation by trialkylchlorostannane.

Mannich reactions of oxazolidines

Abstract 3-Methyl-1,3-oxazolidine and 3,4-dimethyl-5-phenyloxazolidine react with acidic reagents under aprotic conditions to afford reactive intermediates that interact with nucleophilic aromatic substrates and enolsilyl ethers to afford good yields of Mannich bases.

Retro-Mannich reactions of 3-alkyl-3,4-dihydro-2H-1,3-benz e oxazines and the synthesis of axially chiral resorcinarenes

Intermediates involved in the conversion of 3-alkyl-3,4-dihydro-2H-1,3-benz[e]oxazines into 2-N,N-dialkylaminomethylphenol derivatives, using morpholine and other high boiling secondary amines, have been identified and characterised. Additional experiments have established the involvement of o-quinone methide intermediates in the retro-Mannich reactions. Axially chiral resorcinarenes have been prepared by utilising the exchange reactions

The functionalisation of electron rich aromatic compounds with 1,3-oxazolidines and 1,3-dimethylimidazolidine

Abstract N-Phenyl- and N-alkyl-oxazolidines react with alkyl chlorosilanes in the presence of electron rich aromatic compounds with the formation of the expected Mannich bases: 2-methoxycarbonyl-3-methyloxazolidine also reacts with 2-methylfuran in the presence of thionyl chloride to give an α-amino acid derivative: the iminium salt derived from 1,3-dimethylimidazolidine was also shown to react with 2-methylfuran.

The effect of sulphur dioxide on the mannich reactions of phenols

Abstract Regioselectivity in the ortho -dialkylaminomethylation of phenols is greatest, for example in reactions of 2,5-dimethylphenol, when a mixture of the phenol and sulphur dioxide is allowed to stand for several hours before the addition of a bis-(dialkylamino)methane (aminal) or an alkoxydialkylaminomethane (aminol ether).