Trifluoroethanol Promoted Castagnoli-Cushman Cycloadditions of Imines with Homophthalic Anhydride
Thibault Bayles1, Catherine Guillou1
1Institut de Chimie des Substances Naturelles CNRS, Université de Paris-Saclay, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Abstract:
Lactams are essential compounds in medicinal chemistry and key intermediates in the synthesis of natural products. The Castagnoli-Cushman reaction (CCR) of homophthalic anhydride with imines is an exciting method for accessing cyclic densely substituted lactam products. Most CCRs need to be catalyzed or heated. Herein, we report a new, efficient, metal and catalyst-free CCR for the synthesis of poly-substituted 3,4-lactams utilizing the unique properties of trifluoroethanol (TFE). This procedure provides high-speed and smooth access to a broad range of densely substituted 3,4-lactams in good yields and a 100% atom-economical fashion.
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