Quinones Michael reactions

The most extensive mechanistic studies of quinone Michael addition chemistry involve the arylsufinic acids, which yield reduced product (50,51). The sulfones produced in such reactions have been examined electrochemicaHy (48) and kineticaHy (52). The influence of substitutents in the quinone has... 

If an even broader definition of a Michael reaction is used, iminoquinones (19), quinone iminium ions (20), quinone methides (21), etc. can also be viewed as Michael... 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

The Addition of the NH-Gtroup ofPyrazoles to Activated Double Bonds Pyrazoles undergo Michael addition to a,j3-unsaturated acids and esters,618,736,737,737 acrylonitrile,104,483,738 maleic anhydride, acetylene dicarboxylic ester,282,737 a,j8-unsaturated ketones,736 and quinones.104 Alkaline catalysts667 are not essential in this reaction,104 at least for addition to unsaturated nitriles, maleic anhydride, and quinones. The reaction is reversible, and V-pyrazolyl propionic... 

A quinone methide is a relatively unstable species the unsubstituted case has been reported to have a lifetime of 15 seconds in methanol at room temperature [47], However, more substituted, more hindered quinone methides can be prepared in the presence of water and can have long lifetimes (years) in chloroform solutions [48], The instability of quinone methides can be attributed to facile reactions that regenerate an aromatic system. An anion (nucleophile) can add to the a-carbon to rearomatize the system via a familiar Michael reaction [49], The added anion can also be a leaving group (Figure 10.6, step 1) in other words, quinone methide formation is a reversible reaction... 

Michael reactions. 2-Alkylidene derivatives of 1,3-dicarbonyl compounds behave as donors in Michael reactions. Of particular interest is the formation of biaryl precursors with quinones. ... 

The most interesting reactions of the natural quinone-hydroquinone pairs are (a) their reversible one-electron redox reactions, (b) the Michael reactions of quinones, and (c) the formation of polyquinones. Oxidation of tocopherol with FeClj leads to a cleavage of the enol ether and quinone formation (Scheme 7.2.2). 

The nucleophilic reactivity of cysteine has been exploited in Michael reactions with quinones. One example is a water-soluble naphthoquinone, which has been entrapped in chlorophyll-containing vesicles in order to study light-induced electron transfer through a membrane from glutathione to the quinone (Fore, 1983). Another example is an asymmetrical vesicle membrane made of a cysteine quinone carboxylate bolaamphiphile, where all the quinone is localized on the outer surface of the vesicle (see Scheme 7.2.6 Scheme 9.5.1). 

An interesting variation of this reaction is shown in Scheme 2.21 and consists of a Michael reaction between aldehydes and quinones, which results in a procedure for carrying out the formal a-arylation of aldehydes. In this case, the activation of the Michael donor as the corresponding enamine takes place followed by the conjugate addition to the highly electrophilic quinone reagent... 

Scheme 2.21 Enantioselective intermolecular Michael reaction between aldehydes and quinones.

Addition Reactions. The addition of nucleophiles to quinones is often an acid-catalyzed, Michael-type reductive process (7,43,44). The addition of benzenethiol to 1,4-benzoquinone (2) was studied by A. Michael for a better understanding of valence in organic chemistry (45). The presence of the reduced product thiophenyUiydroquinone (52), the cross-oxidation product 2-thiophenyl-1,4-benzoquinone [18232-03-6] (53), and multiple-addition products such as 2,5-(bis(thiophenyl)-l,4-benzoquinone [17058-53-6] (54) and 2,6-bis(thiophenyl)-l,4-benzoquinone [121194-11-4] (55), is typical ofmany such transformations. 

At least two pathways have been proposed for the Nenitzescu reaction. The mechanism outlined below is generally accepted." Illustrated here is the indolization of the 1,4-benzoquinone (4) with ethyl 3-aminocrotonate (5). The mechanism consists of four stages (I) Michael addition of the carbon terminal of the enamine 5 to quinone 4 (II) Oxidation of the resulting hydroquinone 10 to the quinone 11 either by the starting quinone 4 or the quinonimmonium intermediate 13, which is generated at a later stage (HI) Cyclization of the quinone adduct 11, if in the cw-configuration, to the carbinolamine 12 or quinonimmonium intermediate 13 (IV) Reduction of the intermediates 12 or 13 to the 5-hydroxyindole 6 by the initial hydroquinone adduct 7 (or 8, 9,10). 

The best yields of 5-hydroxyindoles are obtained when equimolar amounts of the quinone and enamine are used. An excess of enamine gives rise to non-indolic products derived from reaction of two enamine units and one quinone unit or the product which results from the initial Michael addition of the enamine to the quinone. Use of excess quinone has been reported less frequently, but limited studies indicate no advantage. When 2,5-dichloro-l,4-benzoquinone (32) was treated with a 50% excess of ethyl 3-... 

The mercaptol alcohol rac-14 undergoes facile Michael addition reaction with quinone ketal 13 which is commercially available or can be readily prepared. 

Michael additions to quinones. In the presence of TrC104, enol silyl ethers undergo 1,4-addition to benzoquinone to give adducts that cyclize to benzofurans.1 A similar reaction with diimidoquinones produces indole derivatives. 

The diquinone 300 has been shown to react with a variety of primary amines producing carbazole quinones 301, a process which presumably involves an intermediate such as 302 formed by Michael-type addition. Alkyl-, aryl-, and heteroarylamines and amino acids have been utilized. The reaction failed with p-nitro- and p-acetylanilines neutral and acidic amino acids required base catalysis. Hydroxyl-... 

Closure of the nonaromatid ring of the anthracycline system has been effected by condensation of a 2-(3-oxobutyl)anthraquinone with nitromethane [135]. After the initial Henry reaction, a Michael-type reaction is induced by the quinone carbonyl in spite of the high electron density of the aromatic ring to be attacked, and the site of attack being a donor. 

Addition of water to quinones. The yields of the known Michael addition of water or an alcohol to a 1,4-naphthoquinone such as 5,8-dimethoxy-l,4-naphtho-qninonc arc improved by addition of an oxidant such as Fe2(S04)3 to convert the initial 2-hydroxynuphlhohydroquinone to the corresponding quinone. The presence til ll 1 rcc pert-hydroxy group interferes with the reaction. 

Pyridines add to quinones in Michael-type reactions to give phenolbetaines (64). Many other Michael acceptors behave similarly, e.g. acrylate esters and acrylamides in the presence of acid yield quaternary ions py+CH2CH2COY. Pyridazine at room temperature with maleic anhydride gives the 2 1 adduct (65). 

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