Reactions of thebaine derivatives with trifluoroacetyl acetylenes: [4+2]-addition solely

•Trifluoroacetyl acetylenes produce [4+2]-adducts solely with thebaine derivatives.•N-Acyl derivatives of thebaine must be used to produce the [4+2]-adducts.•The trifluoroacetyl substituted [4+2]-adducts easily rearrange to benzazocines.•The rearrangement can be prevented by the addition of a nucleophile.•Thebaine itself reacts with trifluoroacetyl acetylenes via a nucleophilic pathway.

Trifluoroacetyl acetylenes, highly reactive dienophiles and electrophiles, were used as the probe for study competitive [4+2] vs nucleophilic addition reactions in thebaine series. Unlike thebaine itself that reacts with these electron deficient acetylenes giving rise to the adducts resulted from the nucleophilic attack of the nitrogen at the alkyne carbon, the reactions of N-acyl-N-northebaines with trifluoroacetyl acetylenes furnished the [4+2]-adducts solely. The last ones readily rearranged to the corresponding 3H-furo[4,3,2-fg][3]benzazocine derivatives. So, the use of N-acyl-N-northebaines as the starting materials in the reactions with acetylenic dienophiles provides the general methodology to avoid a formation of the undesirable “nucleophilic” adducts typical for the reactions of the natural alkaloid thebaine.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide