Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

Abstract

Hypervalent iodine-mediated olefin functionalization provides a rapid gateway towards accessing both various heterocyclic cores and functional groups. In this regard, we have developed a Ritter-type alkene functionalization utilizing a PhI(OAc)2 ((diacetoxyiodo)benzene, PIDA)/Lewis acid combination in order to access isoxazoline and pyrazoline cores. Based on allyl ketone oximes and allyl ketone tosylhydrazones, we have developed an alkene oxyamidation and amido-amidation protocol en route to accessing both isoxazoline and pyrazoline cores. Additionally, acetonitrile serves as both the solvent and an amine source in the presence of this PIDA/Lewis acid combination. This operationally straightforward and metal-free protocol provides an easy access to isoxazoline and pyrazoline derivatives.

Alkene Difunctionalization Using Hypervalent Iodine Reagents: Progress and Developments in the Past Ten Years

“…Additionally, their systematic evaluation of amine functional groups provided evidence that the (benzene)sulfonyl group is the key moiety for the amination reaction. Another interesting Ritter-type amidation reaction was also reported by Hong and coworkers (Scheme 16b) [66]. The PIDA/BF 3 ·OEt 2 combination in CH 3 CN provided the unusual Ritter amidation adduct 82 after acetonitrile addition.…”

Hypervalent iodine-mediated synthesis and late-stage functionalization of heterocycles

“…Acetonitrile plays dual role of solvent and the amine source (Scheme 17). 54 Notably, activation of PhI(OAc)2 6 by BF3•OEt2 generates active iodine(III) species in situ, that reacts with 69 to form electrophilic iodonium intermediate 71 which could give desired product 70 through sequential 5-exo-type cyclization and Ritter-typesubstitution using excess acetonitrile as the nucleophile. A variety of ketone oximes with aryl, heteroaryl and alkyl substituents were well tolerated.…”

Synthesis of Oxazoline and Oxazole Derivatives by Hypervalent-Iodine-Mediated Oxidative Cycloaddition Reactions

“…The isoxazoline ring is present in many important heterocycles that are widely used in several areas of chemistry and biomedical sciences. [24][25][26]52 Hypervalent iodine reagents such as (diacetoxyiodo)benzene, [115][116][117][118][119][120][121][122][123][124][125][126][127][128][129] [hydroxy(tosyloxy)iodo]benzene, 130,131 iodosylbenzene, [132][133][134][135] [bis(trifluoroacetoxy)iodo]benzene, 136 (dichloroiodo)benzene, 137 and also in situ generated iodine(III) species, [138][139][140][141] can be used as efficient tools for construction of the isoxazoline ring.…”

“…The oxidative cyclization of allyl ketoximes using (diacetoxyiodo)benzene can produce the corresponding isoxazolines bearing various functional groups. [126][127][128][129] For example, the reaction of allyl ketoximes 81 using (diacetoxyiodo)benzene in the presence of HF•Py as the fluoride source gave the corresponding oxyfluorination compounds 82 (Scheme 23). 128 The obtained isoxazolines 82 can be converted into the monofluoromethyl-substituted -hydroxy ketones via a ring-opening reaction.…”