Synthesis of (E)-2-(1-ferrocenylmethylidene)malonic acid derivatives by a cobalt-catalyzed domino reaction of ethyl diazoacetate, carbon monoxide and ferrocenylimines

The domino reaction of ethyl diazoacetate, carbon monoxide and ferrocenylimines was investigated in the presence of Co2(CO)8 as catalyst. In most cases the main products are 2-(1-ferrocenylmethylidene) malonates formed by an N(1)–C(4) cleavage of the primarily derived β–lactams. The latter compounds could only be isolated when the reaction was carried out at relatively low CO pressure, using an excess of ethyl diazoacetate. trans-N-(tert-Butyl)-3-ethoxycarbonyl-4-ferrocenyl-β-lactam proved to be the most stable one among these compounds and could be isolated in 55% yield. N-alkyl β-lactams were shown to undergo acidic cleavage leading to the E isomers of 2-(1-ferrocenylmethylidene) malonates as the main products. The structures of the two new compounds, (E)-2-ethoxycarbonyl-3-ferrocenyl-N-((R)-1-phenylethyl)-2-propenamide and trans-N-(tert-butyl)-3-ethoxycarbonyl-4-ferrocenyl-β-lactam were confirmed by X-ray crystallography. The relative thermodynamical stability of the products as well as the energetics of the acid-mediated cleavage of the β-lactam ring was elucidated with DFT calculations.

A detailed investigation of the reaction of ethyl diazoacetate and ferrocenylimines was carried out in the presence of Co2(CO)8 catalyst under carbonylation conditions. Presumably, the reaction involves three steps, carbonylation, cycloaddition and cleavage of the β-lactam product of the cycloaddition reaction leading to novel 2-(1-ferrocenylmethylidene)malonic acid derivatives. In most cases the E-isomers of 2-ethoxycarbonyl-3-ferrocenyl-N-alkyl-2-propenamides are the main products. Some of the intermediate β-lactams could also be isolated.Figure optionsDownload as PowerPoint slideHighlights
► Novel ferrocenyl- propenamides were produced by a domino cobalt-catalyzed reaction.
► By the proper choice of conditions, the intermediate β-lactams were also isolated.
► A mechanism is proposed for the cleavage of β-lactams.
► The structures of two products were confirmed by X-ray crystallography.