Oxazoles, from metallated isonitriles

The mechanism of the condensation in Part D probably involves thioformylation of the metallated isocyanoacetate followed by intramolecular 1,1-addition of the tautomeric enethiol to the isonitrile. This thi2izole synthesis is analogous to the formation of oxazoles from acylation of metallated isonitriles with acid chlorides or anhydrides. " Interestingly, ethyl formate does not react with isocyanoacetate under the conditions of this procedure. Ethyl and methyl isocyanoacetate have been prepared in a similar manner by dehydration of the corresponding N-formylglycine esters with phosgene and trichloromethyl chloroformate, respectively. The phosphoryl chloride method described here was provided to the submitters by Professor U. Schollkopf and is based on the procedure of Bohme and Fuchs. The preparation of O-ethyl thioformate in Part C was developed from a report by Ohno, Koi/.uma, and Tsuchihaski. " ... 

This reaction is a modification of Schollkopf s oxazole synthesis2 from acid chlorides and a-metalated isonitriles (equation IT). 

Metalated thiazoles are only stable at low temperatures. The formation of an isonitrile in the procedure below clearly shows this poor stability (compare Ref. [189]). On the other hand the methylthio derivative of benzothiazole is formed in good yield upon addition of a methythiolation reagent to the solution resulting from the interaction between benzothiazole and sodamide in liquid ammonia. This situation may be analogous to the ambident behaviour of 2-lithio-4,5-diphenyl-oxazole [193]. 

Formatiort of Isonitriles. The reaction of butyllithium with oxazole leads to the formation of a metallated species that is in equihbrium with a ring opened isocyanide obtained through a-elimination. The a-isocyanoenolate dominates the equilibrium, and it was found that, by warming this species from —78 °C to room temperature in the presence of an acid chloride, the isolation of 2-substituted isocyanoesters is possible in good to excellent yields (eq 13). These compounds were prepared on multi-gram scale and applied in Ugi reactions. Unlike most isonitriles, they do not exhibit a foul odor. 

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