Unexpected Racemization in the Course of the Acetalization of (+)-( S )-5-Methyl-Wieland-Miescher Ketone with 1,2-Ethanediol and TsOH under Classical Experimental Conditions.

Autor: Leonelli F; Dipartimento di Biologia Ambientale, Università degli Studi La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy., Piergentili I; Dipartimento di Chimica, Università degli Studi La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy., Lucarelli G; Dipartimento di Chimica, Università degli Studi La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy., Migneco LM; Dipartimento di Chimica, Università degli Studi La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy., Marini Bettolo R; Dipartimento di Chimica, Università degli Studi La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2019 Dec 05; Vol. 20 (24). Date of Electronic Publication: 2019 Dec 05.
DOI: 10.3390/ijms20246147
Abstrakt: (+)-( S ) and (-)-( R )-5-methyl-Wieland-Miescher ketone (+)- 1 and (-)- 1 , are important synthons in the diastereo and enantioselective syntheses of biological and/or pharmacological interesting compounds. A key step in these syntheses is the chemoselective C(1)O acetalization to (+)- 5 and (-)- 5 , respectively. Various procedures for this transformation have been described in the literature. Among them, the classical procedure based on the use of 1,2-ethanediol and TsOH in refluxing benzene in the presence of a Dean-Stark apparatus. Within our work on bioactive natural products, it occurred to us to observe the partial racemization of (+)- 5 in the course of the acetalization of (+)- 1 by means of the latter methodology. Aiming to investigate this drawback, which, to our best knowledge, has no precedents in the literature, we acetalized with 1,2-ethanediol and TsOH in refluxing benzene and in the presence of a Dean-Stark apparatus under various experimental conditions, enantiomerically pure (+)- 1 . It was found that the extent of racemization depends on the TsOH/(+)- 1 and 1,2-ethanediol/(+)- 1 ratios. Mechanism hypotheses for this partial and unexpected racemization are provided.
Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Databáze: MEDLINE
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