Quinones, Michael addition, aldehyde

Most examples of quinone dehydrogenations adjacoit to have been earned out on steroidal ketones and are essentially limited to readily enolizable species. Reactions on esters and amides (Table 8) are far less common and, because of their relatively low ease of enolization, require hanh conditions. Thus, unless stabilization of the intermediate carbonium ion is possible, - elevated temperatures and prolonged reaction times are required (Table 8), which increases the incidence of unwanted side reactions. Frequent by-products are those arising as a result of Diels-Alder reactions or Michael addition to the quinone." Allylic alcohols may be rapidly oxidized to aldehydes or ketones under these conditions and requite prior protection. 

As is well known, quinones are easily converted to the corresponding phenol compounds. By using the enantioselective Michael addition of aldehydes to quinones, J0rgensen and co-workers [21] developed the first organocatalytic a-arylation of aldehydes. In the presence of diphenylprolinol silyl ether 7, the a-arylation proceeds well under environmentally friendly conditions (EtOH and H2O as solvent), affording the optically active a-arylated products with high yields and excellent enantioselectivities (Scheme 5.10). 

ThefoUowingdominoreactiondevelopedbyj0rgensenandco-workers [44a] involves enamine activation of aldehydes by diphenylprolinol silyl ether promoting an enantioselective Michael addition onto quinones, followed by an intramolecular hemiacetaliza-tion (Scheme 16.22). The resulting dihydrobenzofiirans were obtained with high yields... 

Perumal has described a four-component sequential protocol that allows the synthesis in good yields of antitubercular 2-aryl-5-methyl-2,3-dihydro-l/f-3-pyrazolones 18 from atylhydrazines, methyl acetoacetate, aromatic aldehydes and 5-naphthol in the presence of / -TSA in water under reflux conditions [13], The reaction proceeds by an initial acid-catalyzed cyclocondensation of the hydrazine and dicarbonyl components to give pyrazolinone 19. A parallel acid-catalyzed condensation between p-naphthol and the aromatic aldehyde affords the intermediate quinone methide 20, and Michael addition of the enol form of 19 onto the exocyclic double bond of 20 furnishes the final product (Scheme 1.9). 

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... 

In 2013, the Chi group realized an NHC-catalyzed asymmetric p-functional-ization reaction of aldehydes via the transformation of saturated aldehydes to formal Michael acceptors via double oxidation. By using the catalyst derived from the chiral amino indanol triazolium salt in combination with quinone as the oxidant, the p-aryl substituted saturated aldehydes were converted to the o,p-unsaturated acyl azolium intermediates which further reacted with 1,3-dicarbonyl compounds or p-keto esters to generate the corresponding 5-lactones. It was found the use of LiCl and 4 A MS as additives was beneficial to improve the ee s of the products. Notably, the p-alkyl substituted saturated aldehydes were not viable substrates, probably due to the reduced acidity of the p-C—H bonds (Scheme 7.118). 

Class III, the reactive chemicals, include epoxides, aldehydes, aziridines, quinones (generally, all alkylating agents) (Hermens Verhaar, 1995). These chemicals (or their activated metabolites) react covalently with nucleophilic sites in cellular biomacromolecules (e.g., through nucleophilic substitution, Michael-type addition, or Schiff-base reactions) or gain an oxidative stress through redox cycling to derive toxic effects (Bradbury et al., 2003). 

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