Process for preparing α-keto acids and derivatives thereof

A method, comprising:

• a) reacting an aldehyde represented by R1CHO with at least two thiols represented by R4—S—H, to give a dithioacetal;
• b) reacting the dithioacetal with a carbonyl-containing electrophile in the presence of a strong base that comprises at least one member selected from the group consisting of n-butyllithium, tert-butyllithium, sodium amide, sodium hydride, potassium hydroxide, and potassium carbonate and hydrolyzing in a solvent represented by R5OH to give an α,α-(dithio)carboxylic acid or a derivative thereof represented by formula (III):
• c) converting the α,α-(dithio)carboxylic acid or derivative thereof represented by formula (III) by acid-catalyzed solvolysis in the presence of at least one molar equivalent of water with release of thiols of the formula R4SH to give at least one of an α-keto acid represented by formula (I) and a compound represented by formula (II)
• wherein
• R1 is an optionally substituted, branched or straight-chain C1-C18-alkyl, C5-C8-cycloalkyl, vinyl, allyl, C6-C10-aryl-C1-C4-alkylene or C4-C9-heteroaryl-C1-C4-alkylene group,
• R2 is —OR′″ or —NR′R″, in which R′ and R″ are the same or different and are each a hydrogen atom or a branched or straight-chain C1-C6-alkyl group, and R′″ is a hydrogen atom, a branched or straight-chain C1-C8-alkyl, C5-C8-cycloalkyl, allyl or a benzyl group, where the alkyl in R′, R″ and R′″ is optionally substituted, or R′″ is an alkaline metal ion, alkaline earth metal ion or a mono- or divalent transition metal ion,
• R3 is the same or different and is a hydrogen atom, a branched or straight-chain C1-C8-alkyl, allyl or a benzyl group, where alkyl and/or benzyl is optionally substituted, or the two R3 radicals together are C2-C8-alkanediyl and together form a ring, or the two R3 and R′″ radicals together are part of a C3-C8-alkanetriyl group of the general formula —R3(CH—)R′″ and together form a bicyclic group,
• R4 is a branched or straight-chain, optionally substituted C1-C6-alkyl, C5-C8-cycloalkyl, allyl or benzyl group, and
• R5 is a hydrogen atom or a branched or straight-chain C1-C6-alkyl group, wherein the acid-catalyzed solvolysis in c) is carried out in the presence of a solvent that comprises at least one of:
• a diol represented by HO—R7—OH, wherein R7 is a branched or straight-chain, optionally substituted C2-C8-alkanediyl group;
• a triol represented by HOR8(CHOH)R9OH, wherein the R8 and R9 radicals together are part of a branched or straight-chain, optionally substituted C3-C8-alkanetriyl group of the general formula —R8(CH—)R9;
• and
• an amine represented by HNR10R11
• wherein R10 and R11 may be the same or different and are each a hydrogen atom or a branched or straight-chain C1-C6-alkyl group,
• with the proviso that R10 and R11 cannot both be a hydrogen atom.