Epoxidations carbene source

Epoxide Formation with Chalcogen-Ylides from Carbene Sources... 

Analogous to epoxides, aziridines can be prepared by the methylenation of imines. In this case, ethyl diazoacetate is the most common source of carbenes. For example, the imine derived from p-chlorobenzaldehyde 148 is converted to the c/j-aziridinyl ester 149 upon treatment with ethyl diazoacetate in the presence of lithium perchlorate <03TL5275>. These conditions have also been applied to a reaction medium of the ionic liquid l-n-butyl-3-methylimidazolium hexafluorophosphate (bmimPFe) with excellent results <03TL2409>. An interesting enantioselective twist to this protocol has been reported, in which a diazoacetate derived from (TJ)-pantolactone 150 is used. This system was applied to the aziridination of trifluoromethyl-substituted aldimines, which were prepared in situ from the corresponding aminals under the catalysis of boron trifluoride etherate <03TL4011>. 

Example 5.9 Consider the retrosynthetic analysis of TM 4.9, a key intermediate in the synthesis of the anti-asthmatic drug salbutamol, and then propose the synthesis. Use the dimsyl anion (MeSOCH2US[a as the source of carbene for cyclization of epoxide. 

Perfluoropropene oxide is a convenient, volatile, thermal source of difluoro-carbene, and its use in the preparation of fluorocyclopropanes has been further exemplified, perfluorinated, polyfluorinated, and hydrocarbon olefins being employed as substrates (see also p. 17) it has also been employed to convert perfluorobut-2-yne into 3,3-difluoro-l,2-bis(trifluoromethyl)cyclo-propene. Qose examination of the reaction between the epoxide and a mixture of cis- and rra .r-l-chloro-l,2-difluoroethylene at ca. 200°C has revealed that stereospecific addition of difluorocarbene takes place, but that loss of configuration can subsequently result from slow thermal isomerization of the cyclopropane product. Thermal decomposition of perfluoropropene oxide at 200 "C in the absence of a trap yields mainly perfiuorocyclo-propane and trifluoroacetyl fluoride together with tetrafluoroethylene, perfluoroisobutene oxide, perfluorobut-l-ene, and poly(difluoromethylene). 

Scheme 7.58 Catalytic cycle proposed for the epoxide formation catalyzed by chalcogen-ylides with diazo-derived carbene as ylide source...

---