Studies in vinyl isonitrile and thiophenium ylid chemistry

Abstract

A method for the reductive formylation of ketoximes was sought. Anhydrous titanium (III) chloride was ineffective, but reaction of cyclohexanone oxime with anhydrous titanium (III) acetate and acetic-formic anhydride in N, M-dimethylformamide solution gave 1-(N-formylamino)cyclohexene(12)in 90% yield. Difficulties in reproducing this reaction were ultimately overcome, and a further 8 one-formamides were prepared by this method. Dehydration of these formamides with phosgene and volatile amines gave azeotropic mixtures of isonitriles and amines. Replacement of the volatile amines with DABCO gave vinyl isonitriles in moderate yield. 8 examples were prepared. A strategy for the synthesis of xanthocillin X was formulated. Condensation of p-hydroxybenzaldehyde with nitromethane followed by borohydride reduction and acetylation gave p-acetoxyphenylnitrosthane(49). Reaction of this with phenyl isocyanate gave the furoxan (47), which was hydrogenated to the oxime (44). This material was inert to the reductive formylation procedure. Reaction of cyclohaxane-1,3-dione with ammonia followed by formylation and dehydration gave l-isocyano-3-hydroxycyclohexa-l,3-diene (67). The rearrangement of thiophenium ylids to thiophene-2-malonates was investigated. 2*-thiopyrans were identified as intermediates in this reaction. The kinetics of the rearrangements were studied. The rearrangement of thiophenium ylids to 2*-thiopyrans was discovered to have first-order kinetics with no long-lived intermediates. The rearrangement of 2*-thiopyrans to thiophene-2-malonates was a two-step process with an unknown long-lived intermediate being formed. A possible mechanistic pathway was proposed.