2,5-Disubstituted oxazoles are synthesized from the corresponding propargylcarboxamides under mild reaction conditions via homogeneous catalysis by AuCl(3). While monitoring the conversion via (1)H NMR spectroscopy, an intermediate 5-methylene-4,5-dihydrooxazole can be observed and accumulated up to 95%, being the first direct and catalytic preparative access to such alkylidene oxazolines. The intermediate was fully characterized and can be trapped at -25 degrees C for several weeks. Deuteration experiments show a stereospecific mode of the two first steps of the reaction.

Dedicated to Professor Johann Mulzer on the occasion of his 60th birthdayThe catalysis of organic reactions by gold compounds has been recently shown to be a powerful tool in synthesis. [1, 2] When gold(i) compounds are used as precatalysts, ligands such as phosphanes [3][4][5][6][7][8] or phosphites [9] can be applied. The gold(iii) precatalysts are mainly simple halides; [2] other examples include one thioether-containing, [10] one phosphite-containing, [9] and organogold(iii) [11] compounds. For the gold-catalyzed phenol synthesis, [12] AuCl 3 usually delivers good results with simple substrates, but with more complicated ones a significant loss of activity is observed. At lower temperature, kinetic studies with our most simple testsubstrate 1 (see Scheme 1) showed that the problem with regard to the loss of activity occurs even with as much as 5 mol % of catalyst ( Figure 1). With small amounts of catalyst, the conversion remains incomplete.We have now tested several gold(i) and gold(iii) complexes with different ligands as catalysts for this reaction. Gold(i) complexes showed low selectivity and led to several side products. Satisfactory results in terms of activity, long-term stability and product-selectivity were obtained only with gold(iii) complexes with pyridine derivatives, some of which contained chelating oxygen functionalities. The most interesting complexes were precatalysts 3-6.[13] The complexes did not suffer deactivation, as shown in Figure 2 for 3-the activity even holds in a second catalytic run. Unlike with AuCl 3 , a mechanistically interesting induction period was observed for 3-6, clearly proving that here the complexes are precatalysts. This is also the reason for the higher activity in the second run, since the catalytically active species is already present and does not have to be formed in a slow reaction.With as little as 0.07 mol % of 3 a complete conversion could be achieved; this corresponds to 1180 instead of the usual 20-50 turnovers. The complexes 4-6 are also highly stable catalysts; a comparison of their activity is depicted in Figure 3: the acceptor-substituted pyridine carboxylate 5 is the most reactive one, followed by the unsubstituted 4 and the donor-substituted 6. Nevertheless, the initial activity of 3, 4, and 6 is lower than that of AuCl 3 . In part, this problem can be solved by switching to dichloromethane/acetonitrile mixtures or even pure dichloromethane (as shown for 3 in Figure 4). In

The substrate scope, the mechanistic aspects of the gold-catalyzed oxazole synthesis, and substrates with different aliphatic, aromatic, and functional groups in the side chain were investigated. Even molecules with several propargyl amide groups could easily be converted, delivering di- and trioxazoles with interesting optical properties. Furthermore, the scope of the gold(I)-catalyzed alkylidene synthesis was investigated. Further functionalizations of these isolable intermediates of the oxazole synthesis were developed and chelate ligands can be obtained. The use of Barluenga's reagent offers a new and mild access to the synthetically valuable iodoalkylideneoxazoles from propargylic amides, this reagent being superior to other sources of halogens.

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