Tosylmethyl isocyanide TosMIC , pyrrole

Isonitrile cyclization provides a useful alternative method of the Knorr type cyclization for pyrrole synthesis. In 1972, Leusen and coworkers reported pyrrole synthesis based on the reaction of tosylmethyl isocyanide (TosMIC) with electron-deficient alkenes (Eq. 10.12).15... 

The stabilised anion of tosylmethyl isocyanide (TosMIC) (or of benzotriazol-l-ylmethyl isocyanide -BetMlC ") adds in Michael fashion to unsaturated ketones and esters, with subsequent closure onto isocyanide carbon, generating the ring. Proton transfer, then elimination of toluenesulfinate generates a 3//-pyrrole that tautomerises to an aromatic pyrrole that is unsubstituted at both a-positions. Addition of the TosMIC anion to unsaturated nitro-compounds gives rise to 2,5-unsubstituted-3-nitropyrroles. ... 

Tosylmethyl isocyanide (TosMIC) was employed in a key step for the synthesis of bicyclic heterocycles from L-glutamic acid <01H(55)2099>, while benzyl isocyanoacetate was utilized for reaction with a-acetoxynitro compound 41 to yield the pyrrole 42, an intermediate in the synthesis of (+)-deoxypyrro oline, a putative cross-link of bone collagen <01JOC11>. 

Van Leusen and co-workers also demonstrated the utility of dilithio-tosylmethyl isocyanide (dilithio-TosMIC) to extend the scope of the application. Dilithio-TosMIC is readily formed from TosMIC and two equivalents of n-butyllithium (BuLi) in THF at -70"C. Dilithio-TosMIC converts ethyl benzoate to oxazole 14 in 70% yield whereas TosMIC monoanion does not react. In addition, unsaturated, conjugated esters (15) react with dilithio-TosMIC exclusively through the ester carbonyl to provide oxazoles (16). On the other hand, use of the softer TosMIC-monoanion provides pyrroles through reaction of the carbon-carbon double bond in the Michael acceptor. 

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