Stoichiometric and catalytic intermolecular Pauson-Khand reactions (PKRs) of dissymmetric fluorinated alkynes were performed, affording regioselectively α-fluorinated cyclopentenones. Ethyl 4,4,4-trifluorobutynoate was an excellent substrate; its reaction with norbornadiene gave the corresponding PKR adduct in good yield and complete regioselectivity. Conjugate addition of nitroalkanes or cyanide to this adduct is stereospecific and entails concomitant loss of a trifluoromethyl group. This reaction can be exploited to prepare cyclopentenones featuring quaternary centers.

10A new approach to the synthesis of 4,5-disubstituted cyclopentenones is described. The strategy is based on the PausonÀKhand (PK) reaction 11 of norbornadiene and N-Boc-propargylamine as an alkyne with a masked leaving group, which can be eliminated at will. This approach to the 12 synthesis of 4,5-disubstituted cyclopentenones overcomes the problem of using the alkylation to introduce the R side chain. As an example, 13 prostane 13-epi-12-oxo-phytodienoic acid (13-epi-12-oxo-PDA) methyl ester was synthesized.

Regioselectivity in Intermolecular Pauson-Khand Reactions of Dissymmetric Fluorinated Alkynes. -The reaction proceeds strictly regioselectively: the fluorinated substituent is always found at the α-position to the enone. -(KIZIRIAN, J.-C.; AIGUABELLA, N.; PESQUER, A.; FUSTERO, S.; BELLO, P.; VERDAGUER, X.; RIERA*, A.; Org. Lett. 12 (2010) 24, 5620-5623, http://dx.

This protocol is based on the Pauson—Khand reaction of alkynes and norbornadiene yielding masked cyclopentadienones with a readily functionalizable double bond.