Methyleneiminium salts Mannich reaction

Enolate-Mediated Mannich Reactions with Methyleneiminium Salts... 

The Mannich reaction has been reviewed comprehensively by Blicke (1942), Reichert (1959), Hell-mann and Opitz (1960), and Tramontini (1973). These reviews also include synthetic applications of Mannich bases. Mechanistic studies of the Mannich reaction have been reviewed by Thompson (1968). Some variants of the Mannich reaction have been covered as subtopics in other reviews for example. Layer (1963) and Harada (1970) have reviewed general additions of stabilized carbanions to imines, while Bdhme and Haake (1976) have reviewed similar additions to methyleneiminium salts. In more specific reviews, Pai and coworkers (1984) have summarized stabilized carbanion additions to 3,4-dihy-droisoquinolines and 3,4-dihydroisoquinolinium salts in connection with the total synthesis of protober-berines and phthalide isoquinolines, and Evans et al. (1982) " have analyzed the stereochemical aspects of ester enolate and silyl ketene acetal additions to imines. 

Competition data for the trifluoroacetylation of a number of heterocycles using trifluoroacetic anhydride at 75 C give the relative rates thiophene (1.0), furan (1.4 x 10 ), 2-methylfuran (1.2 x 10 ) and pyrrole (5.3 x 10 ). Similar values, thiophene (1.0), furan (3.0 x 10 ) and pyrrole (5.0 x 10 ) are obtained for reactions with [C6H7Fe(CO)3]. We have already discussed the fact that thiophene does undergo the Mannich reaction using preformed methyleneiminium salts and therefore it is not surprising that furan also affords the aminomethyl derivatives in reactions with iminium salts. 

The yields of the Mannich bases obtained when a number of methyleneiminium salts were allowed to interact with furan in acetonitrile at room temperature ranged from 66 to 74%. ° A representative example is shown in equation (28). The reasons for the earlier failures remain obscure but the amine would not have been lost under the aqueous reaction conditions. 

A A -Dialkylarylamines react under classical conditions at C-4 if that position is unsubstituted. For example, A. )V-dimethylaniline reacts with formaldehyde and dimethylamine to afford 4-)V, A -dimethyl-amino-A, Af-dimethylbenzylamine in 82% yield (equation 20). Under acidic conditions fragmentation of the initial product can occur, leading to the formation of diarylmethanes. In the reaction of A A -dimethy-laniline with formaldehyde and pyrrolidine the best yield of the Mannich base (44%) is obtained in the presence of 1.5 mol equiv. of acetic acid with 4.0 mol equiv. the yield is only 7%. The reaction of N-methylenemorpholinium chloride with 4-A -morpholinylmethyl-)V,A -dimethylaniline results in the introduction of a second A -morpholinylmethyl residue at the 2-position, but with other iminium chlorides quaternary salts are formed by reaction with the nitrogen of the 4-dialkylaminomethyl group. There is dso a brief report of the use of the mixed A. Af-dialkylmethyleneiminium salt, A -f-butyl-A -methyl-methyleneiminium perchlorate, with A. Af-dimethylaniline. °... 

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