Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

Abstract

A novel reactivity of 1,1,1-trifluoroalkanones is reported, where the reaction with AlCl₃ results in the formation of 1,1-dichloro-1-alkenones. The reaction scope was found to be broad, with various chain lengths and aryl substituents tolerated. For substrates containing an electron-rich aromatic ring, further reactions take place, resulting in bicyclic and/or rearrangement products.

Keywords: Friedel–Crafts alkylation; aluminium trichloride; dichloroalkenes; rearrangement; trifluoroalkanes.

Figure 1

Examples of biologically active 1,1-dichloro-1-alkenes.

Figure 2

a) Common methods for the preparation of 1,1-dichloro-1-alkenes from aldehydes. b) This work: a two-step synthesis of 1,1-dichloro-1-alkenones from nitriles via 1,1,1-trifluoroalkanones.

Scheme 1

The initial attempt for the conversion of 1,1,1-trifluoroalkanone 5a to 1,1-dichloroalkenone 6a.

Scheme 2

Substrate scope for the reaction of 1,1,1 trifluoroalkanones with AlCl₃. ^aPurification (normal or reversed-phase chromatography) required. ^bComplex mixture. ^c5 Days.

Scheme 3

Proposed mechanism for the formation of dichloroalkene 6 from trifluoroalkanone 5.

Scheme 4

Formation of bicyclic ketones 9 and 10 from 1,1,1-trifluoroalkanone 5b using 7 equivalents of AlCl₃.

Scheme 5

Conversion of 1,1,1-trifluoroalkanone 5n to acid chloride 13 with AlCl₃, and possible mechanism.

Scheme 6

Conversion of 1,1,1-trifluoroalkane 16 to bicycle 17 upon treatment with AlCl₃, and possible mechanism.