Mannich base methiodide condensation

An attempt has been made to synthesize the morphinane ring-system in this way, and l-(/3-diethylaminoethyl)-2-keto-1 2 3 4-tetrahydro-naphthalene was converted to [oxxvm] by condensation with the appropriate Mannich base methiodide, the product brominated with N-bromosuccinimide, and finally converted to the quaternary salt [cxxix]. Work on the corresponding N-dimethyl series was abandoned when it was found impossible to obtain the requisite substituted /3-tetralone in a state even approaching purity. The synthesis of [cxxx] has been accomplished by the same method, its production being accompanied by the production of [cxxxi] as a result of further ring-extension [43]. 

Steroid synthesis. In developing a method of cyclization which has been of immeasurable -walue in the total synthesis of steroids, Robinson at first experimented with the condensation of ketones with methyl vinyl ketone itself, but encountered difficulties associated with the tendency of the ketone to polymerize. He then turned to possible prectnsors and met with some success with methyl /3-chloroacetyl ketone, CHsCOCHzCH CI. Still better, however, was the methiodide (2) of the Mannich base (1), l-diethylamino-3-butanone. Treated with a strong base such as sodamide in... 

The Robinson annulation is the reaction of alkali metal derivatives of cyclohexanones with a-,p>unsaturated methyl ketones to produce cycloketones and polycycloketones. The standard method for Robinson annulation is exemplified in the mechanism shown above. For the synthesis of the 1,5-diketone side chain, the enolate nucleophile reacts with a Michael acceptor this Michael acceptor is usually a substituted vinyl ketone or the parent methyl vinyl ketone (MVK), although the latter gives low yield due to its propensity to polymerize under the standard reaction conditions. To overcome the drawbacks for using MVK, Robinson, McQuillin and Du Feu introduced the Robinson-Mannich variation of the annulation reaction. This modification uses a quatemized Mannich base formed from the vinyl entity the Maimich base is made in situ and acts as a methyl vinyl ketone precursor after it is converted to its methiodides. The formed methiodides of the Mannich adduct 4-(trimethylamino-2-butanone) is condensed with sodioderivatives of ketones or with the parent ketone in the presence of sodium ethoxide. 

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