Chemoselective cycloisomerization of O-alkenylbenzamides via concomitant 1,2-aryl migration/elimination mediated by hypervalent iodine reagents.

As an ambident nucleophile, controlling the reaction selectivities of nitrogen and oxygen atoms in amide moiety is a challenging issue in organic synthesis. Herein, we present a chemodivergent cycloisomerization approach to construct isoquinolinone and iminoisocoumarin skeletons from o-alkenylbenzamide derivatives. The chemo-controllable strategy employed an exclusive 1,2-aryl migration/elimination cascade, enabled by different hypervalent iodine species generated in situ from the reaction of iodosobenzene (PhIO) with MeOH or 2,4,6-tris-isopropylbenzene sulfonic acid. DFT studies revealed that the nitrogen and oxygen atoms of the intermediates in the two reaction systems have different nucleophilicities and thus produce the selectivity of N or O-attack modes.

Stereospecific Dehydroxytrifluoromethylthiolation of Alcohols Promoted by a Combination of Hypervalent Trifluoromethylthio-iodine(III) Reagent and N-Heterocyclic Carbene.

Direct dehydroxytrifluoromethylthiolation of alcohols is an attractive strategy for accessing CF3S-containing compounds. Herein, we report a method for dehydroxytrifluoromethylthiolation of alcohols by using the combination of hypervalent iodine(III) reagent TFTI and N-heterocyclic carbenes. This method shows excellent stereospecificity and chemoselectivity to give a product with clean inversion of the configuration of hydroxyl groups as well as can be used for late-stage modification of structurally complex alcohols. The reaction mechanism is proposed with experimental and computational evidence.

Late-Stage Dehydroxyazidation of Alcohols Promoted by Trifunctional Hypervalent Azido-Iodine(III) Reagents.

The development of convenient new methods for the synthesis of organic azides is highly desirable. Herein, we report a practical method for dehydroxyazidation of alcohols via an SN 2 pathway involving PPh3 and trifunctional benziodazolone-based hypervalent azido-iodine(III) reagents, which function as an electrophilic center, an azido source, and a base. This mild, chemoselective method was used for late-stage azidation of structurally complex alcohols, as well as for a new synthetic route to the antiepileptic drug rufinamide. The reaction mechanism was also investigated both experimentally and computationally.

Ring Expansion Fluorination of Unactivated Cyclopropanes Mediated by a New Monofluoroiodane(III) Reagent.

Herein, we report a new strategy for carbon-carbon bond scission and intramolecular ring expansion fluorination of unactivated cyclopropanes, which was accomplished with a new hypervalent fluoroiodane(III) reagent 1. This novel method delivers medicinally relevant 4-fully substituted fluoropiperidines in moderate to high yields with excellent regio- and diastereoselectivity. Reagent 1, which has an N-acetylbenziodazole framework, was readily synthesized via three steps in 76 % overall yield and was characterized by NMR spectroscopy and X-ray crystallography. Owing to the presence of a secondary I⋅⋅⋅O bonding interaction between the λ3 -iodane atom and the carbonyl oxygen of the acetyl group of the N-acetylbenziodazole framework, 1 has excellent stability and can be stored at ambient temperature for 6 months without any detectable decomposition. Density functional theory calculations and experimental studies showed that the reaction proceeds via a carbocation intermediate that readily combines with a fluoride ion to generate the product.