How the Structural Elucidation of the Natural Product Stephanosporin Led to New Developments in Aryl Radical and Medicinal Chemistry

Abstract

The intent of this account is to provide a focused overview of recent developments in aryl radical chemistry, especially extensions and applications of the Meerwein arylation and the Gomberg-Bachmann reaction. Although most of the reactions and methods described were discovered on the basis of earlier findings made by our group or logically depend on newly discovered reactivities or mechanistic principles, the rapid evolution of radical chemistry can nevertheless be traced back to the behavior of the natural product stephanosporin, which is capable of liberating 2-chloro-4-nitrophenol via an aryl radical intermediate.

Development of immunoliposomes containing cytotoxic gold payloads against HER2-positive breast cancers

“…Here, we chose gold( i ) chloro derivatives [AuCl(PR 3 )] containing PR 3 as ligands: PPh 3 ( 1 ) and PEt 3 ( 2 ), 36 as the compounds to be encapsulated into liposomes (structures in Fig. S1‡).…”

“…Compounds ([AuCl(PPh 3 )] ( 1 ), [AuCl(PEt 3 )] ( 2 ) and [AuCl(BODIPY-PPh 2 )] ( 3 ) respectively), were all synthesized as reported. 36,55,58 2-Iminothiolane (Traut's reagent) and the ELISA kit were purchased from Sigma-Aldrich. Trastuzumab and pertuzumab were purchased in-house at Memorial Sloan Kettering Cancer Center.…”

Recent Development of Aryl Diazonium Chemistry for the Derivatization of Aromatic Compounds

“…The aryl radical addition to aromatic compounds with aryl diazonium salts, which was first discovered by Gomberg and Bachmann, is a highly useful method for synthesizing unsymmetrical biaryls. Several outstanding reviews have discussed biaryl synthesis with arene diazonium salts over the past six years. − This radical-type C–H bond arylation has attracted interest from the synthetic community. , Recent advances in this area mainly focus on developing transition-metal-catalyzed, organic initiator-mediated, photoinduced, and electrolysis processes (Scheme ). The transition-metal-catalyzed C–H bond functionalization and dual photoredox/transition-metal-catalyzed approaches will be summarized in the following section.…”

“…58−63 This radical-type C−H bond arylation has attracted interest from the synthetic community. 64,65 Recent advances in this area mainly focus on developing transitionmetal-catalyzed, organic initiator-mediated, photoinduced, and electrolysis processes (Scheme 23). The transition-metalcatalyzed C−H bond functionalization and dual photoredox/ transition-metal-catalyzed approaches will be summarized in the following section.…”

Boronic Acid Mediated Carbocyanation of Olefins and Vinylation of Alkyl Iodides

“…We report herein the development of a tin‐free strategy that uses phenylboronic acids to mediate the three‐component carbocyanation of olefins and the vinylation of alkyl halides under radical conditions. It has been shown that alkyl radicals may be selectively generated through the rapid abstraction ( k ≈ 10 9 m –1 s –1 ) of the iodine atom from an alkyl iodide by an aryl radical, which is formed by the fragmentation of arylboronic acids under oxidative conditions . This fast abstraction outperforms other competitive processes that might occur in the medium, including the addition to sulfonyl derivatives or the olefin partner .…”