Understanding and Modulating Indolyne Regioselectivities

Abstract

Heterocyclic arynes hold much promise for applications in modern synthetic chemistry. One particular class of hetarynes is those derived from the indole heterocycle (i.e., indolynes). Indolynes can be generated under mild fluoride-based reaction conditions using silyltriflate precursors. Indolyne-trapping experiments provide access to benzenoid-substituted indoles in a controlled manner with synthetically useful yields. Regioselectivities can be predicted prior to experiments using simple calculations, ultimately allowing for the modulation of selectivities by careful design. This strategy has enabled a concise synthesis of indolactam V.

A Synthetic Route to Tetrahydro-1H-azepino[4,3,2-cd]indoles via Ring-Opening Cyclization of Activated Azetidines with 4-Bromoindole: Toward a Vasopressin V2 Receptor Antagonist

“…Alkaloids with 3,4-fused indole tricyclic moieties including 6-, 7-, 8-, 9-, and 12-ring sizes having various carbon, nitrogen, and oxygen linkages are found in nature and exhibit high biological activities. Many attempts have been made to synthesize them. − Functionalization at the 4-position of indole is a difficult task under the normal electrophilic reaction, as 3-, 5-, or 7-positions are preferred for this purpose. , Among indole derivatives, azepinoindole-based alkaloids and other related natural products possess azepinoindoles as the core structures in many drug molecules ,, and show remarkable antifungal, antibacterial, antimicrobial, anti -HIV, antimalarial activities along with some metabolic activity against hypertension and act as a receptor antagonist . In the past few decades, azepinoindoles attracted synthetic organic and medicinal chemists because of their wide applicability, such as (+)- syn -clavicipitic acid, , (−)- anti -clavicipitic acid, , (−)-aurantioclavine, vasopressin V2 receptor antagonist, etc.…”

Total Synthesis of Phenanthroindolizidines Using Strained Azacyclic Alkynes

“…One promising tactic involves the use of heterocyclic arynes, such as 1 – 3 (Figure ). These short-lived intermediates can be manipulated in ways reminiscent of aryne functionalization processes − but come with the added benefit of having a heteroatom incorporated in their core. , Pyridynes (e.g., 1 ) have been most thoroughly studied and have been used in a number of total syntheses. , For example, total syntheses of ellipticine ( 6 ) were enabled by Diels–Alder reactions with in situ-generated pyridynes. , Indolynes (e.g., 2 ) and their π-extended carbazolyne counterparts (e.g., 3 ) are also highly valuable synthetic building blocks, with several applications in total synthesis being reported. − For example, the interception of an indolyne and carbazolyne, respectively, was instrumental in enabling the total syntheses of N -methylwelwitindolinone C isothiocyanate ( 7 ) and tubingensin B ( 8 ) …”