Fluorine as a Traceless Directing Group for the Regiodivergent Synthesis of Indoles and Tryptophans

Abstract

Despite ample evidence for the unique reactivity offered by hypervalent F-iodanes, mechanistic investigations fall far behind. In order to shed light on the unusual behavior of such F-reagents, we conducted computational and experimental studies on the chemodivergent transformation of styrenes. We identified the spirocyclic F-cyclopropane as the common intermediate for both the C, H-fluorination and C, H-amination pathways. The fate of this key compound is determined by the extent of cationic charge delocalization controlled by the N-substituents. Exploiting this phenomenon, a multitude of different transformations have become available, leading, i.e., to the regiodivergent synthesis of indoles and tryptophans.

Cyclic Haloiodanes: Syntheses, Applications and Fundamental Studies

“…Moreover, omission of molecular sieves results in the formation of benzylic ketones ( Scheme 17 ,b ). This reaction is shown to work smoothly for a range of substrates, including ones with amides [40] …”

“…Treatment with a strong acid afforded the corresponding aza‐indole ( Scheme 15). Gulder , Rehbein and co‐workers later reported that the same kinds of products could be obtained directly in absence of carbonyl as internal nucleophile from 2‐aminostyrene derivatives in good to quantitative yields ( Scheme 16 ,a ) [40] . An excess of pyridinium p ‐toluenesulfonate (PPTS) was added for some substrates.…”

“…Gulder and co‐workers later tested chloroiodane 2b and bromoiodane 2c in the same conditions, but the six‐membered rings were formed instead ( Scheme 14). [40] Use of 2b lead to a low conversion of the starting material; use of Willgerodt ’s reagent (PhICl 2 ) instead afforded complete conversion exclusively into the corresponding six‐membered ring 49 , isolated with a 78 % yield.…”

Hypervalent Iodine‐Mediated and Traceless Fluorine‐Oriented: Synthesis of 5‐Methyl‐1,2,3,4‐tetrahydropyridine from Unactivated Alkenes

“…Moreover, as a Lewis acid, BF 3 ⋅ Et 2 O can realize the selective activation of C−F bonds, which can fulfil some special coupling reactions [9a–c] . Therefore, we envisage that this strategy of “traceless guide group” can provide a basis [8b] for the intramolecular oxidative coupling reaction of alkenes by hypervalent aryl‐iodine. In this article, we firstly reported the intramolecular coupling reaction for the formation of Csp 2 −N bond via hypervalent iodine‐mediated and traceless fluorine‐oriented, which provided a facile synthesis strategy to the 5‐methyl‐1,2,3,4‐tetrahydropyridine skeleton directly from unactivated alkenes.…”

Synthesis of Functionalized Indoles via Palladium-Catalyzed Cyclization of N-(2-allylphenyl) Benzamide: A Method for Synthesis of Indomethacin Precursor

“…Substituted N-benzoylindole is one of the most attractive skeletons, since it is a privileged structure of many pharmacologically active compounds such as indomethacin. Besides, the only method reported to construct substituted N-benzoyl indole is the C-H-amination of styrenes using hypervalent iodine as the oxidant (Figure 2b) [35,36]. However, it should be noted that the oxidants of these two methods are not commercially available.…”