Additions acid chlorides, oxazole

In 1972, van Leusen, Hoogenboom and Siderius introduced the utility of TosMIC for the synthesis of azoles (pyrroles, oxazoles, imidazoles, thiazoles, etc.) by delivering a C-N-C fragment to polarized double bonds. In addition to the synthesis of 5-phenyloxazole, they also described reaction of TosMIC with /7-nitro- and /7-chloro-benzaldehyde (3) to provide analogous oxazoles 4 in 91% and 57% yield, respectively. Reaction of TosMIC with acid chlorides, anhydrides, or esters leads to oxazoles in which the tosyl group is retained. For example, reaction of acetic anhydride and TosMIC furnish oxazole 5 in 73% yield. ... 

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. " ... 

The reaction of acylsilanes with acid chlorides in the presence of A1C13 leads to furans (Table 9.41) [45]. In these reactions an acyl cation initiates the addition with ensuing silyl migration yielding an intermediate vinyl cation. Attack of the carbonyl oxygen followed by proton loss affords the observed products (Scheme 9.16). An analogous reaction with nitrosyl fluoroborate provides a route to oxazoles (Table 9.42) [65]. The nitrosyl cation serves as the electrophile in this application. 

An especially difficult acylation of the resin-bound, stericaUy hindered D-Piz(Z) derivative 3 (Scheme 3) was achieved by using silver cyanide as additive. While Fmoc-Ile-Cl itself led to a yield of only 50%, the efficiency was increased when the reaction was carried out in the presence of silver cyanide. The exact mechanism of silver cyanide catalysis is not clear, but it was shown that silver cyanide effects conversion of the acid chloride to the oxazol-5(4//)-one. Although the hydrogen cyanide formed during this process may catalyze the reaction of the oxazol-5(4//)-one, the results of separate hydrogen cyanide catalyzed coupling of preformed oxazol-5(4//)-one did not match exactly the silver cyanide catalyzed reaction of the acid chloride. ... 

Recently, Addie and Taylor extended the synthetic utility of TosMIC by developing conditions to effect desulfonylation of a 5-substituted 4-tosyloxazole 405 (Scheme 1.109, p. 90). Their plan was to generate the dianion of 5-methyl-4-tosyloxazole 402 followed by quenching with an electrophile to produce a 5-substituted-4-tosyloxazole 404. Desulfonylation of 404 would provide a novel entry to 5-substituted oxazoles 405, thereby avoiding the use of toxic methyl isocyanide. In addition, desulfonylation of the 5-substituted 4-tosyloxazoles 406 normally obtained from reaction of TosMIC with an ester, acid chloride, or acid anhydride would further broaden the scope and use of this reaction. 

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