Chemoselective CaO-Mediated Acylation of Alcohols and Amines in 2-Methyltetrahydrofuran

Authors

  • Dr. Vittorio Pace,

    Corresponding author
    1. Department of Drug and Natural Product Synthesis, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna (Austria), Fax: (+43) 1-4277-9556
    • Department of Drug and Natural Product Synthesis, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna (Austria), Fax: (+43) 1-4277-9556
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  • Dr. Pilar Hoyos,

    1. Organic and Pharmaceutical Chemistry Department, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28049 Madrid (Spain)
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  • Prof. Dr. Andrés R. Alcántara,

    1. Organic and Pharmaceutical Chemistry Department, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28049 Madrid (Spain)
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  • Prof. Dr. Wolfgang Holzer

    1. Department of Drug and Natural Product Synthesis, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna (Austria), Fax: (+43) 1-4277-9556
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Abstract

Calcium oxide is proposed as an innocuous acid scavenger for the chemoselective synthesis of amide- and ester-type compounds. Although these molecules have wide spread applications in organic and pharmaceutical chemistry, and a large number of routes have been designed for their synthesis, the development of more efficient and environmentally friendly acylation strategies remains an ongoing challenge. The use of CaO allows for the stoichiometric acylation of primary alcohols in the presence of phenols or tertiary alcohols; amines can also be subjected to acylation reactions in the presence of hydroxyl groups. Chirality is obtained through acylation if the starting material is an optically pure alcohol or if a chiral acylating agent is used. Furthermore, the use of 2-methyltetrahydrofuran (2-MeTHF), a more ecofriendly solvent, leads to maximized yields. This protocol is successfully applied to the synthesis of an interesting N-aryloxazolidin-2-one intermediate for the preparation of linezolid-type compounds.

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