Study On Cyclopropanelation Of N-alkoxy α,β-unsaturated Amide Promoted By Iodine(Ⅲ)

Cyclopropane,as the smallest carbocyclic skeleton,has large ring tension and unique bonding methods that make it significantly different from other cyclic compounds.The special structure and properties make it very important for biological activity,so it is found in many natural products.For example,in the medical field,many mature drugs also contain pharmacophores such as Odana catib（Cathepsin K inhibitor）,Singulair（anti-asthma）,and ciprofloxacin（broad-spectrum antibiotics）.Hypervalent iodine compounds are widely used in organic synthesis as an environmentally friendly reagent.Its stable properties,low toxicity,abundant species,and insensitivity to air and water have caused explosive growth in the field of hypervalent iodine chemistry in the past decade.Many reactions involving hypervalent iodine continue to appear,showing great potential in the construction of C-C bonds,C-hetero bonds,oxidation reactions,and functional group conversion.Some of them have become personal reagents,such as Togni’s reagent,Koser’s reagent,Dess-Martin’s reagent,etc.Common hypervalent iodine reagents have also been commercialized.Since Professor Yu Jinquan first used N-methoxyamide as a directing group in 2008to catalyze the activation of C-H bonds,N-alkoxyamide has been widely used as a directing group in the field of C-H bonds activation catalyzed by transition metals.In addition,N-alkoxyamide as an amide derivative also has special properties not found in ordinary amides,such as the formation of nitrenium ion,nitrogen radical,cyclization,substitution and other reactions under metal-free conditions.In this paper,N-alkoxyα,β-unsaturated amides with alkyne bonds were used as starting materials,trifluoroethanol was used as the solvent,and cheap and easily available（diacetoxyiodo）benzene was used as the oxidant.Cyclopropane pyrrolidone dihydrooxazine skeleton was efficiently constructed at room temperature under open conditions.The reaction has the advantages of mild conditions,no metal,short time,high chemical selectivity,and easy operation.31 new compounds were successfully synthesized by this method.The reaction has a good functional group tolerance,and three conversion reactions were tried on the product.The possible intermediates for the reaction were calculated by density functional theory,and for the first time,a carbocation-mediated cyclopropanation mechanism under metal-free conditions was proposed.The structures of all the target compounds have been characterized by ¹H NMR,¹³C NMR and HRMS,and the structure of the target compound was determined by the crystal X-ray diffraction of compound 2t.