Copper catalysis carbene insertion

Lactams, and /S-lactams in particular, are interesting owing to their occurrence in biologically active compounds such as antibiotics related to penicillines. Insertion reactions of carbenes offer useful access to poly heterocyclic systems contain a -lactam nucleus, particularly when using rhodium and copper catalysis. Moreover, palladium catalyzed carbonyla-tion of azirines affords )S-lactam derivatives [93] in one step. 

Insertion of a ketocarbene moiety into a C—O bond of orthoesters is normally performed with catalysis by BF3 Et20. Copper(II) trifiouromethanesulfonate was found to be a similarly efficient catalyst also, at least in some cases, whereas Rh2(OAc)4 was much less suited to promote this transformation l60). Besides the C/O insertion product 343, the alcohol insertion product 344 and, in reactions with ethyl diazoacetate, the formal carbene dimers were obtained. In agreement with BF3 EtzO, Cu(OTf)2 did not bring about insertion into a C—O bond of trimethyl... 

Cycloaddition of the carbene derived from 205 to bis(trimethylsilyl)acetylene yields the expected cyclopropene in low yield both photochemically (20%) and under catalysis by copper triflate at 80 °C (10-13%)119. The latter version of the reaction is accompanied by [3 + 2] cycloaddition of the diazo compound to the alkyne, and the photochemical route yields a by-product which obviously comes from carbenic C,H insertion at a SiMe3 group of the alkyne. 

Diazo compounds, with or without metal catalysis, are well-known sources of carbenes. For synthetic purposes a metal catalyst is used. The diazo compounds employed are usually a- to an electron-withdrawing group, such as an ester or a ketone, for stability. In the early days, copper powder was the catalyst of choice, but now salts of rhodium are favoured. The chemistry that results looks very like the chemistry of free carbenes, involving cyclopropanation of alkenes, cyclopropenation of alkynes, C-H insertion reactions and nucleophilic trapping. As with other reactions in this chapter, free carbenes are not involved. Rhodium-carbene complexes are responsible for the chemistry. This has enormous consequences for the synthetic applications of the carbenes - not only does the metal tame the ferocity of the carbene, but it also allows control of the chemo-, regio- and stereoselectivity of the reaction by the choice of ligands. 

A three-component cross-coupling of A-tosylhydrazones, terminal alkynes and allyl halides yields allyl allenes, using copper(I) catalysis a copper carbene migratory insertion is proposed. 27... 

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