Cu(I)-Catalyzed Synthesis of Polysubstituted Furans

Significance

Reported is the efficient Cu(I)-catalyzed synthesis of tri- and tetra-substituted furans 2, 3 and 5 from bis-propargylic esters 1. The proposed mechanism involves the formation of a 2-furylcarbene complex which may be trapped with a variety of electrophiles including ethyl diazoacetate (EDA), oxygen and silanes or germanes to give furan derivatives 2, 3 and 5, respectively, in moderate to excellent yield. The reaction was found to tolerate a wide range of functionality at the alkyne terminus (R^¹) including alkyl, aryl trimethylsilyl and alkenyl groups. A number of different esters (R^²) such as acetate, propanoate, pivalate and acrylate also proved amenable to cyclization.

Comment

The furan-ring system is a key feature in many natural products and pharmaceutical compounds, and is a versatile building block in synthetic chemistry (see book below). The current method represents a novel, regioselective synthesis of highly substituted furans from readily accessible starting materials, and compares favorably with the traditional synthesis of furan-3-carboxylates from 1,3-dicarbonyls (Feist-Benary reaction, see book below). The substrate scope and functional group tolerance were well studied, and preliminary studies on the reactivity of the proposed 2-furylcarbene complex are also presented.

Book: B. König, In Science of Synthesis, Vol. 9; G. Maas, Ed.; Georg Thieme Verlag: Stuttgart, New York, 2000, 183-286.