Convenient synthesis of new functionalized cyclopropanes from monoterpenic olefines

Five new cyclopropyl-ketoacids were prepared in good yields from monoterpenic olefines using solid-liquid phase transfer catalysis (SL-PTC) dichlorocyclopropanation reaction followed by oxidative cleavage with RuCl 3 -NaIO 4 system. The nonchlorinated cyclopropanes were obtained by sodium/methanol reduction of the corresponding gem -dichlorocyclopropanes


Introduction
The enormous importance of functionalized cyclopropanes, in various scientific fields, lies in their diverse biological activity 1 and their usefulness as valuable building blocks in organic synthesis. 2Recently [3][4][5] , we have reported the synthesis of new functionalized cyclopropanes from terpenic olefins.This synthesis involves a periselective gem-dihalocyclopropanation reaction (under SL-PTC conditions) 6 of one of the terpenic olefine double bounds followed by an oxidative cleavage of the other, using RuCl 3 -NaIO 4 catalytic system. 7This facile and convenient methodology has been adapted for the preparation of five new cyclopropyl-ketoacids which are reported herein.sodium hydroxide concentration and temperature, the dichlorocarbene addition reaction to limonene 1 always gives the nondesired product 7 15 .In order to direct the dichlorocyclopropanation reaction towards the exocyclic double bound, 1 was first epoxidized under aerobic epoxidation conditions described recently 16 .The resulting epoxylimonene 8 16 , obtained as cis/trans (40/60) diastereomeric mixture in 91 % yield, was then treated with dichlorocarbene (generated in-situ under the same conditions described above) to provide the diclorocyclopropane 9 17 in 90 % yield, as a mixture of four stereoisomers (two faces of the double bond in 8 are likely not sterically equivalent) (Scheme 3).

Scheme 3
All the obtained products 5-9 were fully characterised by their mass and NMR spectroscopic data.
Before oxidation of obtained cyclopropanes 10, 11 and 12, we have first checked the oxidative cleavage reaction on compound 12 in order to optimize the reaction conditions.Table 1 summarises some representative results obtained with 12 using freshly prepared RuO4 as catalyst and NaIO4 (stoichoimetric) as oxidant.An increase of the substrate/catalyst ratio (100 instead 50) led as expected to a slower reaction but interestingly high yield into the acid.With a substrat/catalyst ratio 500, only 10% of ketoacid 15 were obtained after 48 hours (entry 6).On the other hand a decrease in the NaIO4/substrate ratio had a very detrimental effect on conversion (entry 4).The best result (85% yield) was obtained at room temperature after 30 hours with 8 equivalent of NaIO 4 and substrate/catalyst ratio 50 (entry 2).
The spectroscopic data of the three newly prepared cyclopropyl-ketoacids 13, 14 and 15 are consistent with the assigned structures, mainly characterized by 1 H NMR spectroscopy; the signals for cyclopropanic protons are ranged between 0.1-0.6 ppm and the signals for ethylenic protons disappeared.Their 13 C NMR spectra reveal carbonyl groups resonance at about 209-213 ppm (ketone carbonyl group) and 178-179 ppm (acid carbonyl group).Their spectroscopic data are in full accordance with the attributed structures which were mainly characterized by 13 C NMR spectroscopy.The cyclopropanic CCl 2 groups appeared at 70-75 ppm, whereas acid and ketone carbonyl groups signals revealed at 176 ppm and 208-212 ppm respectively.

Conclusion
We have described a simple and convenient synthesis of new cyclopropyl-ketoacids starting from limonene, terpinolene and γ-terpinene.The nonchlorinated cyclopropyl-ketoacids 13-15 were prepared by a periselective dichlorocyclopropanation reaction (under SL-PTC conditions) of the corresponding monoterpenes followed by a sodium/methanol reduction of the gemdichlorocyclopropanes 5, 6 and 9.The oxidative cleavage of the obtained cyclopropanes 10-12 with system RuCl 3 -NaIO 4 , afforded the desired cyclopropyl-ketoacids 13-15 in 53-67 % overall yields.It is worth mentioning that in the case of limonene, we were compelled to epoxidize the internal double bound in order that the ensuing dichlorocyclopropanation reaction would occur at the exocyclic one.The dichlorocyclopropyl-ketoacids 16 and 17 were similarly obtained via a direct oxidative cleavage from the corresponding precursors 5 and 6 in 56% and 62 % overall yields, respectively.