Michael addition acceptors

Critical position/ factor Effect on carcinogenic potential Rationale 

Substitution t if a, 3-double bond, or Stabilizing the reactive group 

Size 1 with increase of alkyl chain Decrease of alkylating/cross- 

Functionality t if bifunctional or multifunctional Cross-linking potential 

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Fluorme-containing Michael addition acceptors have been used as synthons, a portion of a molecule recognizably related to a simpler molecule, for the introduction of fluorine into the organic molecules Their reactions with enamines and ketones lead to a condensarion-cyclization process... 

The trifluorinated a, J-ethylenic ketone shown in equation 36 was prepared by two different methods and behaves like a Michael addition acceptor in reactions... 

Figure 14.21 Michael addition acceptors (i) carbonyl, (ii) sulfonyl, and (iii) phosphoryl group.

Table 14.15 Critical structural features which can affect the carcinogenicity of Michael addition acceptors.

Reduce the cross-linking potential by avoiding bi- or polyfunctional Michael addition acceptors. 

The use of heteroaryl vinyl sulfides and vinyl dithiocarbamates (166) as hetero-Michael addition acceptors has been described. Combined chelating and electron-withdrawing effects were postulated to stabilize the transient anionic species and allow smooth Michael-induced ring closure to produce C-glycosides (167).191... 

The trifluorinated a./ -unsaturatcd ketone 43 can be prepared by two different methods and behaves like a Michael addition acceptor in reaction with nucleophilic species.1 Is reaction with an enamine gives an annulation product 44. This sequence constitutes a method to build up a ring bearing a trifluoromethyl group. 

It has been shown that benzils (323) react with Michael addition acceptors (324) in the presence of a catalytic amount of cyanide ion to yield 1,4-diketones (325). The authors proposed that (325) are produced through the formation of the O-aroylmandelonitrile anion, followed by Michael addition and rearrangement of the aroyl group with decyanation (see Scheme 77). The mechanism of the base-catalysed ring fission of 2,2-dihydroxyindane-l,3-diones has been investigated and the pathway set out in Scheme 78 has been proposed for the transformation. The base-catalysed ring... 

Another category of reactive enones is 4-deoxy-l,2-0-isopropylidene-L-glycero-pent-4-enopyrano-3-ulose, originally synthesized by Klemer and Jung (25) and currently explored by us as an extremely useful new chiral building block for stereoselective functionalization reactions, especially as Michael addition acceptors (Scheme 6). 

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