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 4a-c is described. This process started with the preparation of 2-fluoroalkyl substituted propargyl vinyl ether 3a-d by treatment of a mixture of individual ethyl alpha-per(poly)fluoroalkyl acetates 1a-d and propargyl alcohol 2 in CH2Cl2 with the mixed base (Na2CO3/TEA) at ambient temperature. When heated in toluene at 80degreesC. 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 4a-c (Z/E mixture). The reaction of ethyl (X-per(poly)fluoroalkyl acetate I with I-phenyl propargyl alcohol 5 in refluxing CH2Cl2 in the presence of the mixed base (Na2CO3/TEA) directly afforded the corresponding unsaturated fluoroalkyl ketone 6a-c in one pot. In the presence of NaH, the reaction of ethyl 3-halo-3-fluoroalkylacrylates 8a-b with 1,1-dimethyl propargyl alcohol 9 at -50degreesC to 0degreesC also gave the unsaturated fluoroalkyl ketones 10a-b in one pot. The difluorovinyl propargyl ether 11 produced by reduction of 2-bromodifluoromethyl substituted propargyl vinyl ether 3b rearranged in hot benzene to give the corresponding allene 12 hearing a gem-difluoromethylene group in the middle of the aliphatic chain. (C) 2003 Elsevier Science Ltd. All rights reserved.