ABSTRACT:The cyclization of N-alkenylamides catalyzed by iodoarenes under oxidative conditions is presented. Five-, six-and seven-membered rings with a range of substitutions can be prepared by this route. Preliminary data from the use of chiral iodoarenes as precatalysts show that enantiocontrol is feasible.Research in hypervalent iodine chemistry has gained considerable momentum in recent years.1 In particular, the emergence of catalytic and enantioselective processes with iodine(III) species is starting to make these competitive with metal-catalysis. 2Recent examples include the catalytic enantioselective spirolactonization of phenols, 3 dioxygenation of styrenes, 4 and intramolecular C-H/C-H cross-coupling.5 This ability to effect "metallike" synthetic transformations without the toxicity, supply or cost issues of transition metal salts is attractive.We have previously developed catalytic methods using insitu generated hypervalent iodine species and have reported the oxidative cyclization of δ-alkynyl β-ketoesters 6 and the enantioselective oxidative cyclization of δ-ketoacids. 7 We wished to extend this catalytic concept to the formation of useful heterocycles such as oxazolines and dihydrooxazines. Oxazolines are common structural motifs found in natural products with notable biological activities, e.g. the leupyrrins, active against fungi and eukaryotic cells, 8 and the bistratamides, which possess anticancer properties (Figure 1). 9 Dihydrooxazines are useful synthetic intermediates in organic synthesis 10 and derivatives possessing fungicidal activity have also been reported. 11In this Communication, we disclose our results on the catalytic cyclization of unsaturated amides to give oxazolines, dihydrooxazines and larger ring analogs. At the beginning of our study, Moon and Harned published the stoichiometric hypervalent iodine mediated cyclization of N-allylamides (Scheme 1). 12Their report was limited to five membered ring formation, the use of terminal alkenes and the products described were all racemic. Herein, we reveal catalytic conditions for the cyclization and expand the scope of the process to include other ring sizes and more substituted alkenes. In addition, we have achieved enantiocontrol in this cyclization using chiral iodoarenes. There are few examples in the literature of iodoarene-catalyzed reactions involving alkenes. 4,13 One issue with these processes is the potential for undesired oxidation of the olefin in preference to the iodoarene especially as common oxidants for the conversion of iodoarenes into the active iodine(III) species include peracids.

Two complementary iodoarene-catalyzed methods for the preparation of 2-oxazolines are presented. The first involves the cyclization of N-propargylamides and the second involves the cyclization of β-amidoketones. These are proposed to proceed through different mechanisms and have different substrate scopes.

Starting from N‐allyl amides, a protocol for the preparation of isoxazoline substituted methanol derivatives is elaborated.