An Arylative Aziridination Process toward Aspidosperma Alkaloids

Abstract

An arylative aziridination process has been developed from dibrominated phenols containing a Fukuyama sulfonamide on the lateral chain. A two-step procedure involving the formation of a dienone by a phenol oxidation reaction mediated by a hypervalent iodine reagent (Kita reaction) followed by an intramolecular arylative aziridination process was used. This second step occurred under mild conditions via a Michael-Smiles ring-closure cascade, producing sulfur dioxide as the only byproduct. Additionally, a stereoselective approach was observed with tyrosine derivatives. This transformation respects the rules of green chemistry and atom economy. These new polyfunctionalized scaffolds could offer several synthetic possibilities for the total synthesis of natural products such as the main core of Aspidosperma alkaloids.Aziridines 1a-f are small heterocycles that can be used to produce a variety of more complex structures, including natural products. With epoxides 1g and cyclopropanes, 1h they represent the most important three-membered ring systems. 1 Therefore, they have attracted the attention of the synthetic community and several processes have been described in the literature. Currently, the consensus is that sustainable, environmentally benign routes to desirable synthetic targets should be atom economical and free of protecting groups 2 to respect the concept of "green chemistry." With this idea in mind, we were recently interested in the development of new processes enabling the rapid formation of functionalized heterocycles promoted by a Michael-Smiles tandem process 3 as well as their extension to halogen-dienone systems to yield cyclopropanes. 4 Encouraged by these results, we decided to extend this approach to a nitrogen nucleophile to yield aziridines. These heterocycles were produced from reactive dienones that were readily

Iodanes as multi-tools for the total synthesis of complex natural products

“…As an alternative for this α-arylation process to produce the indole core present in such alkaloids, we developed a method 51 in tandem with a phenol dearomatization reaction that enables the ortho -nitro-aryl subunit to be transferred from a nosyl protecting group. This strategy using a functional protecting group approach 52 a is an alternative to the protecting group-free method.…”

Hypervalent‐Iodine(III)‐Mediated Tandem Oxidative Dearomatization/Aziridination of Phenolic Amines: Synthesis of Functionalized Unactivated Aziridines

“…To explore the synthetic utility of this protocol, a gram-scale reaction of 1 a was performed by using finely ground PhI(OAc) 2 to afford tricyclic aziridine 2 a with analogous efficiency in 69 % yield (entry 2). In an attempt to increase the structural diversity of functionalized aziridines, as shown in Scheme 2, tandem oxidative aziridination involving p-quinone monoketal intermediate was investigated, [16] and the reaction of meta-phenolic amine 1 p having γ-methoxy instead of α'-methoxy in 1 a under the standard conditions resulted in the formation of sterically congested, chemically unstable homoallylic aziridine 2 p, which was reduced in situ to give the hydroxy-aziridine 2 p-a in 58 % yield and 4 : 1 dr. Structurally, the stereochemistry of β-2 p-a as major isomer was clearly assigned by X-ray crystallographic analysis.…”