The 1,4-Benzoxathiane, 2- or 3-substituted, scaffold is an important moiety, present in a wide number of therapeutic agents. Despite its abundance in bioactive molecules, it is chemically unexploited and there are only a couple of examples in literature reporting the benzoxathiane in its enantiopure form. In the present communication, taking advantage of the established synthetic method used for the synthesis of 1,4-benzodioxane carboxamides [1], we report a completely innovative and easy method for the preparation of both 2- and 3- substituted 2,3-dihydro-1,4-benzoxathiine [2]. By using the (S)-phenylethylamine, we defined for the first time the absolute configuration of each amide and, after hydrolysis, of its corresponding acid. This was possible thanks to the significant differences in terms of 1H-NMR spectra and of other physical chemical properties. Two peculiar synthetic pathways were developed and followed for the achievement of the two regioisomeric carboxamides, due to the liability of the 3- substituted moiety. To do so, we also considered how the regioselectivity in the benzoxathiane ring closure strongly relies on the nature of both solvent and substrate [3]. 2-Mercaptophenol was ad hoc condensed, achieving the two enantiopure amides, which were further hydrolyzed in acid conditions, letting to the achievement of the corresponding 1,4-benzoxathian carboxylic acids. [1] Fumagalli L, Bolchi C, Bavo F, Pallavicini M., Tetrahedron Lett. 2016;57(18):2009-2011. [2] Straniero V, Lodigiani G, Suigo L, Valoti E., Chirality., 2022;34(8):1053‐1064. [3] Casiraghi A, Valoti E, Suigo L, Artasensi A, Sorvillo E, Straniero V. J Org Chem. 2018;83(21):13217-13227.

RESOLUTION VIA DIASTEREOMERIC AMIDES OF ENANTIOPURE 1,4-BENZOXATHIAN-2- AND 3-CARBOXYLIC ACIDS AND DETERMINATION OF THEIR CONFIGURATION / G. Lodigiani, V. Straniero, L. Suigo, E. Valoti. ((Intervento presentato al 21. convegno Merck Young Chemists' Symposium 2022 tenutosi a Rimini : 21-23 novembre nel 2022.

RESOLUTION VIA DIASTEREOMERIC AMIDES OF ENANTIOPURE 1,4-BENZOXATHIAN-2- AND 3-CARBOXYLIC ACIDS AND DETERMINATION OF THEIR CONFIGURATION

G. Lodigiani;V. Straniero;L. Suigo;E. Valoti
2022

Abstract

The 1,4-Benzoxathiane, 2- or 3-substituted, scaffold is an important moiety, present in a wide number of therapeutic agents. Despite its abundance in bioactive molecules, it is chemically unexploited and there are only a couple of examples in literature reporting the benzoxathiane in its enantiopure form. In the present communication, taking advantage of the established synthetic method used for the synthesis of 1,4-benzodioxane carboxamides [1], we report a completely innovative and easy method for the preparation of both 2- and 3- substituted 2,3-dihydro-1,4-benzoxathiine [2]. By using the (S)-phenylethylamine, we defined for the first time the absolute configuration of each amide and, after hydrolysis, of its corresponding acid. This was possible thanks to the significant differences in terms of 1H-NMR spectra and of other physical chemical properties. Two peculiar synthetic pathways were developed and followed for the achievement of the two regioisomeric carboxamides, due to the liability of the 3- substituted moiety. To do so, we also considered how the regioselectivity in the benzoxathiane ring closure strongly relies on the nature of both solvent and substrate [3]. 2-Mercaptophenol was ad hoc condensed, achieving the two enantiopure amides, which were further hydrolyzed in acid conditions, letting to the achievement of the corresponding 1,4-benzoxathian carboxylic acids. [1] Fumagalli L, Bolchi C, Bavo F, Pallavicini M., Tetrahedron Lett. 2016;57(18):2009-2011. [2] Straniero V, Lodigiani G, Suigo L, Valoti E., Chirality., 2022;34(8):1053‐1064. [3] Casiraghi A, Valoti E, Suigo L, Artasensi A, Sorvillo E, Straniero V. J Org Chem. 2018;83(21):13217-13227.
Settore CHIM/08 - Chimica Farmaceutica
Società Chimica Italiana
RESOLUTION VIA DIASTEREOMERIC AMIDES OF ENANTIOPURE 1,4-BENZOXATHIAN-2- AND 3-CARBOXYLIC ACIDS AND DETERMINATION OF THEIR CONFIGURATION / G. Lodigiani, V. Straniero, L. Suigo, E. Valoti. ((Intervento presentato al 21. convegno Merck Young Chemists' Symposium 2022 tenutosi a Rimini : 21-23 novembre nel 2022.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/948489
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