SYNTHESIS OF INDIVIDUAL ISOMERS OF 2-(3-CHLOROPROP-2-EN-1-YL)CYCLOHEXANONE

Recently, vinyl chlorides has been increasingly used as electrophilic partners in various cross-coupling reactions. In contrast to inaccessible and expensive vinyl bromides and iodides, in many cases vinyl chlorides are highly active in the presence of not only traditional palladium complexes, but also economical and safe compounds of iron, cobalt and nickel. Earlier, we reported on the development of new approaches to the getting of stereochemically pure (E)- and (Z)-vinyl chlorides and their successful use at the synthesis of medicines and insect pheromones. Continuing this work, an effective method of the synthesis of (E)- and (Z)-isomers of 2-(3-chloroprop-2-en-1-yl)cyclohexanone - convenient precursors of 2-(alk-2-en-1-yl)cyclohexanones, known flavors and intermediates in the synthesis of polycyclic compounds was developed. In the reaction of ethyl 2-oxocyclohexanecarboxylate with the (E)- and (Z)-isomers of 1,3-dichloropropene under the phase-transfer catalysis conditions in the presence of K2CO3, the corresponding (E)- and (Z)-isomers of ethyl 1-(3-chloroprop-2-en-1-yl)-2-oxocyclohexanecarboxylate were obtained in high yields (80-86%), without allyl rearrangement. The complete retention of the configuration of the chlorovinyl group is observed. Standard methods of the decarboxylation of isomers of ethyl 1-(3-chloroprop-2-en-1-yl)-2-oxocyclohexanecarboxylate under acidic or basic conditions result in very average yields of the corresponding chlorovinyl ketones. The best results were obtained by their decarbalkoxylation in slightly modernized Krapcho conditions. Carrying out reaction in N-methylpyrrolidone at 140-150 °C in the presence of 3 eq. LiCl and 2 eq. of H2O leads to individual (E)- and (Z)-isomers of 2-(3-chloroprop-2-en-1-yl)cyclohexanone in 79-82% yields and a stereochemical purity of ~ 99%. The structure of the obtained compounds were confirmed by HRGC, NMR, and GC/MS data. The configuration of the vinyl group was proved by the coupling constants of the vinyl hydrogens, equal to 13.2-13.4 and 7.0-7.3 Hz for the (E)- and (Z)-products, respectively, as well as by the downfield shift of the allyl carbon atom of trans-isomers by ~4 ppm as compared to the cis-analogs.