Diversificação estrutural tardia via arilação de heckmatsuda: síntese e caracterização estrutural de arilcanfenos

Abstract

Late-stage diversification (LSD) of natural products (NP) is a way to change the structure of NP that has been studied by researchers who want to find functions that are like those of natural compounds. Heck-type reactions such as Heck-Matsuda enable the structural diversification of these compounds in a regioselective manner. The Heck-Matsuda arylation (HM) is a crosscoupling that uses arenediazonium salts as arylating agents and palladium(II) sources as precatalysts in a catalytic process capable of forming carbon-carbon bonds. Given the importance of this event, we decided to employ it as a tool for structural diversification of natural products abundant in nature and with relevant biological potential, such as camphene (1). Camphene (1) is a monoterpene found in essential oils from several plants and shows antiviral, antibacterial, and antifungal biological value. In this sense, the studies described in this work include the investigation of the Heck-Matsuda-type arylation process using arene diazonium tetrafluoroborate salts (2), which contain both electron-donating and electron-withdrawing groups to verify the generality and scope of occurrence for a substrate with a non-active olefin, as in the case of camphene (1). These efforts made it possible to synthesize a small semisynthetic compound library of camphene (1) herein called camphene HM adducts (4) and predict the bioactive potential of the compiled ones through in silico testing with free software. All the products formed were characterized using 1D NMR (1H and 13C) and infrared (IR) spectroscopy, and the geometry of the double bond was assigned as E from the 2D NMR studies (COSY, NOESY, HMQC, and HMBC) performed for one of the prepared adducts.