Mechanism and Origin of the Unexpected Chemoselectivity in Fluorocyclization of o-Styryl Benzamides with a Hypervalent Fluoroiodane Reagent

Abstract

The mechanism and origin of the unexpected chemoselectivity in fluorocyclization of o-styryl benzamide with a cyclic hypervalent fluoroiodane reagent were explored with DFT calculations. The calculations suggested an alternative mechanism that is broadly similar to, but also critically different from, the previously proposed mechanism for the formation of an unexpected structurally novel seven-membered 4-fluoro-1,3-benzoxazepine. The amide group of o-styryl benzamide was revealed to be crucial for activating the fluoroiodane reagent and facilitating C-F bond formation. In contrast to the popular electrophilic N-F reagent Selectfluor, the F atom in the fluoroiodane reagent is nucleophilic, and the I(III) atom is the most electrophilic site, thus inducing a completely different reactivity pattern. The insights reported here will be valuable for the further development of new reactions based on the hypervalent fluoroiodane reagent.

Diethylaminosulfur Trifluoride (DAST)-Mediated Intramolecular Benzannulation of o-Allylchalcones: Synthesis of 3-Fluorotetralins

“…Among them, there are few reports on the synthesis of mono-fluorinated bicycles by different fluorinating reagent-promoted intramolecular tandem cyclization/fluorination processes, as shown in Scheme 1. [14][15][16][17][18][19][20][21] These elegant synthetic routes have exhibited some advantages, including easy operation, high sitespecific selectivity, and optimal reaction conditions.…”

“…16 Cheng et al explored the possibility of Selectfluor-mediated efficient installation of the primary fluoro group on a benzo[d]oxazine skeleton via fluorocyclization of o-styryl benzamides. 17 By the addition of N-fluorobenzenesulfonimide (NFSI), Ma et al developed a stereoselective synthesis of fluorinated dihydroquinolinones via one-pot intermolecular Knoevenagel condensation of o-amino -keto esters with aryl aldehydes followed by the -fluorination of the resulting azaflavones. 18 With the use of Selectfluor and catalytic amounts of Ag(I), You et al described that one-pot intramolecular cyclization/fluorination of 2-alkynylanilines afforded a variety of structurally diverse fluorinated indole derivatives.…”

Hypervalent Fluoroiodane‐Triggered Synthesis of Fluoro‐Azabenzoxazepines and Azaindoles

“…In contrast to the common electrophilic aza fluorination agents, such as Selectfluor, employing 1 gave rise to a novel class of heterocyclic products, the fluorinated benzoxazepines 3 (Scheme d) . Their synthesis involves an unprecedented fluorination‐rearrangement‐cyclization‐cascade reaction . To explore the general applicability of this method, we set out to further explore the boundaries of this transformation by expanding the substrate scope of this fluorocyclization.…”

Cyclic Haloiodanes: Syntheses, Applications and Fundamental Studies

“…The peculiar reaction outcome depending on the nature of the fluorinating agent used raised mechanistic interest. This reaction was thus studied by Xue , Cheng and co‐workers using density functional theory (DFT) [39] . The computed mechanism suggests that fluoroiodane 2a first performs an addition reaction on the alkene to form the intermediate 44 ( Scheme 12).…”