Mannich radical-type

The classical Mannich aminomethylation is one of the most important ionic carbon-carbon bond forming reactions in organic chemistry [35]. However, only substituents with electron-withdrawing groups are suitable for the ionic addition. Electron-donating groups directly bonded to the carbon-centered radical favor nucleophilic radical addition to methylene-iminium salts. Thus, the radical-type Mannich reaction provides products which are complementary to those obtained with the classical ionic reaction. 

More recently, Porta and co-workers have reported a free-radical Mannich type reaction based on the selective a-CH aminomethylation of ethers by a Ti(III)/t-BuOOH system under aqueous acidic conditions (Equation 14.27) [34]. 

Finally, in the treatment of azulcne Mannich base methiodidc with zinc, the participation of a radical species of the type R—CH2- is proposed in order to explain the formation of the corresponding dimeric product. ... 

To date, no known bisindole alkaloid has been shown to be only an artefact. In addition, no experimental evidence exists which undermines the assumption that bisindole alkaloids are actually formed from the completed monomeric partners. Support for this idea is derived from the kind of reactions apparently necessary to effect such dimerisations which are known biogenetic processes amine-aldehyde condensations, Mannich reactions, Michael additions, Friedel-Craft type condensations, Diels-Alder type processes, radical coupling etc. The observation that the skeletal distribution amongst monomeric alkaloids is reflected throughout the dimeric series lends further support. 

In several instances, Mannich-type cyclizations can be carried out expeditiously under photochemical conditions. The photochemistry of iminium ions is dominated by pathways in which the excited state im-inium ion serves as a one-electron acceptor. The photophysical and photochemical ramifications of such single-electron transfer (SET) processes as applied to excited state iminium ions have been expertly reviewed. In short, one-electron transfer to excited state iminium ions occurs rapidly from one of several electron donors electron rich alkenes, aromatic hydrocarbons, alcohols and ethers. Alternatively, an excited state donor, usually aromatic, can transfer an electron to a ground state iminium ion to afford the same reactive intermediates. Scheme 46 adumbrates the two pathways that have found most application in intramolecular cyclizations. Simple alkenes and aromatic hydrocarbons will typically suffer addition processes (pathway A). However, alkenic and aromatic systems with allylic or benzylic groups more electrofugal than hydrogen e.g. silicon, tin) commonly undergo elimination reactions (pathway B) to generate the reactive radical pair. 

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