Carbonylation of Propargyl Carbamates with Palladium(II) Bisoxazoline Catalysts: Efficient Synthesis of 5‐Methoxy‐3(2H)‐furanones

3(2H)-Furanones are well known as basic components of natural products which display a wide range of characteristic physiological properties. A number of synthetic strategies and pharmaceutically active substances have been reported. The transition metal catalyzed reaction of unsaturated systems has recently proven to be a powerful method for the construction of a variety of carboand heterocycles. Recently, we reported the cyclization/carbonylation/cyclization-coupling reaction (CCC-coupling reaction) of propargyl acetates, amides, ureas, g-propynyl-1,3-diketones, Npropargylanilines, and o-alkynylphenols catalyzed by palladium(II) bisoxazoline (box) complexes (Scheme 1a). Symmetrical ketones bearing two oxazoles, cyclic orthoesters, oxabicyclic groups, quinolones, and benzofurans were obtained in a one-step procedure. The triple bond of the substrate coordinates to palladium(II) and undergoes nucleophilic attack by the intramolecular nucleophilic oxygen atom with subsequent CO insertion to produce either the acyl palladium intermediate A1 or A2. Coordination of the triple bond of the second molecule induces the second cyclization. Reductive elimination then leads to formation of a ketone with two heterocyclic groups. In the absence of the box ligand, methanolysis of the acyl palladium intermediate (L=MeO , neutral complex) occurs predominantly. We believe that the box ligand enhances the p-electrophilicity of palladium(II), and thus promotes coordination of the second triple bond to the acyl palladium intermediateA1 orA2, thus leading to the dimerization reaction. At the same time, methanolysis of the acyl palladium intermediate A1 or A2 is suppressed by coordination of the second triple bond. To extend the concept of this tandem reaction, we planned to investigate the [(box)Pd]-catalyzed carbonylation reaction of analogous substrates, that is, carbamates 1 (Scheme 1b). Based on our earlier results, the acyl palladium intermediate A3 should be produced by a similar reaction of the carbamates 1, and methanolysis of A3 should be suppressed by coordination of the triple bond of a second molecule. If the rate of decarboxylation of A3 is fast compared to that of the CCC-coupling reaction, a new type of cascade reaction is expected. Consequently, we report herein a new preparation of the 5-methoxy-3(2H)-furanones 2 by the cyclization/ carbonylation/decarboxylation/cyclization sequence of the propargyl carbamates 1 catalyzed by [(box)Pd] complexes. Initially, we selected 1a as a standard substrate to search for potential catalysts (Table 1). The reaction of 1a with [(CH3CN)2PdCl2] (5 mol%) in the presence of p-benzoquinone (1.5 equiv) in methanol under a carbon monoxide atmosphere (balloon) generated the acrylate 3a in 40% yield along with a mixture of unidentified compounds (Table 1, entry 1). The structure of 3a was determined by X-ray crystallographic analysis. The use of [(Ph3P)2PdCl2] and Pd(tfa)2 afforded 3a in poor yields (entries 2 and 3). In addition, [{( )-sparteine}Pd(tfa)2] and [(2,2’-bipyridine)PdCl2] did not show catalytic activity. An attempt was then made to use the box ligand according to our hypothesis, and thus resulted in a new reaction pathway to afford the 5methoxy-3(2H)-furanones 2. Although the use of the box ligands L2 and L3 (Figure 1) resulted in the formation of 2a in Scheme 1. a) Previous work on CCC-coupling reaction. b) This work.