Marschalk alkylation

Marschalk alkylation (8, 456). The intramolecular Marschalk alkylation is useful in syntheses of the tetracyclic ring system of the cytostatic anthracycline antibiotics. A bimolecular version of the reaction involves condensation of 1 with glyoxylic acid and alcoholic KOH. The product of this reaction is reduced and esterified to afford 2 in 33% overall yield. Less than 5% of the isomeric product 3 is obtained. 9-Deoxy-e-rhodomycinone 4 is available from 2 in two steps (details not provided). ... 

Marschalk alkylation of unsymmetrical leuco compounds such as 83 under alkaline conditions occurs selectively at the 2-position [69,70], while reaction in the presence of piperidinium acetate (Lewis conditions) [71] occurs at the 3-position [70]. This allows regiospecific syntheses in which the regiochemistry of formation of ring A is controlled by the distant 4-hydroxyl function. This is... 

Manchalk reaction. Some years ago Marschalk et al. found that leucoquinizarin (1), prepared in situ by reduction of quinizarin with alkaline dithionite, reacts with aldehydes to form 2-alkylquinizarins (2). It is not possible to obtain 2,3-disubstituted quinizarins in this way. Lewis found that pyridinium acetate with isopropyl alcohol as solvent is superior to a base or an acid catalyst for this reaction yields as high as 90% of 2 can be obtained. In addition, aromatic aldehydes can be used successfully. The leuco forms of 2 can be alkylated in this way to give 2,3-dialkylquinizarins in 40-70% yields. 

Annelation of hydroxyanthraquinones. Leucoquinizarin (2), the reduction product of quinizarin with sodium dithionite, reacts with sucdndialdehyde (excess) to give, after oxygenation, the naphthacenequinone derivative 3 in 62% yield. This annelation is related to the Marschalk reaction by which an alkyl group is introduced into the 2-position of a 1-hydroxyanthraquinone by reaction of an aldehyde with the leuco derivative of the quinone. 

Electrophilic reactions on the electron-deficient anthraquinone are normally not possible. However, in 1936 Marschalk described the facile alkylation of the anthraquinone nucleus by aldehydes after reduction of the quinone to the electron-rich hydroquinone using dithionite [34]. This strategy might be called a redox Umpolung , since the chemical reactivity of the anthracene core is reversed by the redox reaction. 

---