Electrophilic cyclization of α- and β-geranyl acetates by mercury(II) trifluoroacetate

Abstract

Etectrophilic cyclization of !3-geranyl acetate promoted by mercury(u) trifluoroacctate leads to mixtures of ct-and 7-5ctH-eyclogeranyl acetate derivatives and 6a-hydroxy-Sc~//-and 6~-hydroxy-513H-cyclogeranyl acetate derivatives mereurated at the C-3 atom. The ratio of the unsaturated and hydroxymercurated products depends on the reaction conditions. cL-Geranyl acetate reacts with mercury(u) trifluoroacetate to give a mixture of 6c~-hydroxy5all-and 6a-hydroxy-513H-geranyt acetates, mereurated at C-9, with an equatorial mercurated methylene group at C-4. The mercury-containing groups in mercurated cyclogeranyl derivatives can easily be reduced or replaced by an oxygen-containing functional group; this constitutes a convenient route to polyfunctional cyclogeranyl derivatives that are difficult to obtain.Key words: electrophilic cyclization, ct-and 13-geranyl acetates, mercury(n) trffiuoroacetate, cyclogeranyl derivatives.Electrophilic cyclization of ct-(1) and J3-geranyl acetates (2) promoted by mercury salts is of certain synthetic interest, because, owing to the possibility of easy replacement of the mercury-containing residue by an oxygen-containing functional group, 1 it opens a way to difficultly accessible cyclogeranyl derivatives with functional groups in the gem-dimethyl position or at the C-3 atom (from here on, the steroid numbering of atoms is used). The alternative pathway to cyclogeranyl derivatives hydroxylated at the above-mentioned positions, which involves cyclization of the corresponding atiphatic epoximonoterpenoids with a terminal epoxide ring is of low efficiency. [2][3][4][5] In this paper, we report the results of a study of the cyclization of ct-and 13-geranyl acetates 1 and 2 promoted by Hg(OCOCF3)2. It should be noted that cyclization of 13-geranyl acetate 2 in the presence of this reagent has been carried out earlier; 6 ct-(3a) and , [-(4a) cyclogeranyl acetates mercurated at the C-3 atom were isolated in an overall yield of 24%.By the reaction of 13-geranyl acetate 2 with Hg(OCOCF3) 2 at room temperature in l-nitropropane followed by treatment of the reaction mixture with a solution of NaCI, we obtained a mixture of compounds, which was separated by chromatography on a column with silica gel. The least polar fraction contained unreacted geranyl acetate 2. The next fraction in order of polarity consisted of a mixture (1 : 7) of mercurated cyclic compounds 3b and 4b (overall yield 45.7%) (Scheme I), whose structures are confirmed by the fact that the mixture of 3b and 4b was reduced by NaBH4 under standard conditions 7 to give a mixture (1 : 7,