Synthesis of (R)-3-Methylphthalide by Reductive Cyclization of a 2-Acylarylcarboxylate Using the Chiral Boronic Ester TarB-H and Sodium Borohydride

Title:Synthesis of (R)-3-Methylphthalide by Reductive Cyclization of a 2-Acylarylcarboxylate Using the Chiral Boronic Ester TarB-H and Sodium Borohydride

Volume: 13 Issue: 9

Author(s): Aline Aparecida Nunes de Souza and Jason Guy Taylor

Affiliation:

Keywords: Phthalides, asymmetric reduction, sodium borohydride, TarB–H, cyclization, lactonization.

Abstract: Background: Phthalides are pervasive benzolactone structural frameworks in nature and have a broad profile of biological activities. Catalytic asymmetric reduction with the in situ lactonization of 2-acylarylcarboxylate compounds is an efficient strategy for chiral phthalide synthesis. The tartaric acid-derived reagent TarB–X is capable of mediating the asymmetric reduction of aromatic ketones using either LiBH₄ or NaBH₄ as the reductant. Up until now, the asymmetric reduction by Tarb- H/NaBH₄ had not been applied to the synthesis of chiral phthalides.

Methods: The requsite substrate, methyl 2-acetylbenzoate was obtained by a two step reaction starting from phthalic anhydride and maloninc acid. Tarb-H was obtained by treatment of L-(+)-tartaric acid with phenylboronic acid. The catalyst and NaBH₄ were reacted with methyl 2-acetylbenzoate at room temperature for 1 h. The structure of (R)-3-Methylphthalide was established by NMR and mass spectrometry and its enantiomeric excess was determined by HPLC. The relative configuration was deduced by comparison of the optical rotation with data given in the literature.

Results: (R)-3-Methylphthalide was obtained in moderte yield and high enantiomeric excess.

Conclusion: (R)-3-methylphthalide was prepared in high enantiomeric excesses using an inexpensive and easily synthesized tartaric acid derived boronic ester (TarB–H) with sodium borohydride. The chiral phthalide was obtained in an open flask by reductive cyclization of a 2-acylarylcarboxylate.

Cite this article as:

Souza Aparecida Nunes de Aline and Taylor Guy Jason, Synthesis of (R)-3-Methylphthalide by Reductive Cyclization of a 2-Acylarylcarboxylate Using the Chiral Boronic Ester TarB-H and Sodium Borohydride, Letters in Organic Chemistry 2016; 13 (9) . https://dx.doi.org/10.2174/1570178613666161021154112

DOI https://dx.doi.org/10.2174/1570178613666161021154112	Print ISSN 1570-1786
Publisher Name Bentham Science Publisher	Online ISSN 1875-6255