The synthesis of 2,4-dienyl fluoroalkyl ketones by a tandem three-stage sequence of propargyl 2-fluoroalkylvinyl ether formation, Claisen rearrangement, and allene-to-conjugated diene isomerization

A tandem three stages process to a series of trifluoromethyl and halodifluoromethyl 2,4-unsaturated ketones is described. This process started with the preparation of 2-fluoroalkyl substituted propargyl vinyl ether by treatment of a mixture of individual ethyl α-per(poly)fluoroalkyl acetates and propargyl alcohol in CH2Cl2 with the mixed base (Na2CO3/TEA) at ambient temperature. When heated in toluene at 80°C, these ethers readily underwent a tandem propargyl-allenyl Claisen rearrangement and isomerization of the resultant 3,4-dienone to give 2,4-unsaturated fluoroalkyl ketones (Z/E mixture). The reaction of ethyl α-per(poly)fluoroalkyl acetate with 1-phenyl propargyl alcohol in refluxing CH2Cl2 in the presence of the mixed base (Na2CO3/TEA) directly afforded the corresponding unsaturated fluoroalkyl ketone in one pot. In the presence of NaH, the reaction of ethyl 3-halo-3-fluoroalkylacrylates with 1,1-dimethyl propargyl alcohol at −50°C to 0°C also gave the unsaturated fluoroalkyl ketones in one pot. The difluorovinyl propargyl ether produced by reduction of 2-bromodifluoromethyl substituted propargyl vinyl ether rearranged in hot benzene to give the corresponding allene bearing a gem-difluoromethylene group in the middle of the aliphatic chain.