Bismuth has recently been shown to be able to maneuver between different oxidation states, enabling access to unique redox cycles that can be harnessed in the context of organic synthesis. Indeed, various catalytic Bi redox platforms have been discovered and revealed emerging opportunities in the field of main group redox catalysis. The goal of this perspective is to provide an overview of the synthetic methodologies that have been developed to date, which capitalize on the Bi redox cycling. Recent catalytic methods via low-valent Bi(II)/Bi(III), Bi(I)/Bi(III), and high-valent Bi(III)/Bi(V) redox couples are covered as well as their underlying mechanisms and key intermediates. In addition, we illustrate different design strategies stabilizing low-valent and high-valent bismuth species, and highlight the characteristic reactivity of bismuth complexes, compared to the lighter p -block and d -block elements. Although it is not redox catalysis in nature, we also discuss a recent example of non-Lewis acid, redox-neutral Bi(III) catalysis proceeding through catalytic organometallic steps. We close by discussing opportunities and future directions in this emerging field of catalysis. We hope that this Perspective will provide synthetic chemists with guiding principles for the future development of catalytic transformations employing bismuth.

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The endoplasmic reticulum (ER) is an essential compartment of the biosynthesis, folding, assembly, and trafficking of secretory and transmembrane proteins, and consequently, eukaryotic cells possess specialized machineries to ensure that the ER enables the proteins to acquire adequate folding and maturation for maintaining protein homeostasis, a process which is termed proteostasis. However, a large variety of physiological and pathological perturbations lead to the accumulation of misfolded proteins in the ER, which is referred to as ER stress. To resolve ER stress and restore proteostasis, cells have evolutionary conserved protein quality-control machineries of the ER, consisting of the unfolded protein response (UPR) of the ER, ER-associated degradation (ERAD), and autophagy. Furthermore, protein quality-control machineries of the ER play pivotal roles in the control of differentiation, progression of cell cycle, inflammation, immunity, and aging. Therefore, severe and non-resolvable ER stress is closely associated with tumor development, aggressiveness, and response to therapies for cancer. In this review, we highlight current knowledge in the molecular understanding and physiological relevance of protein quality control of the ER and discuss new insights into how protein quality control of the ER is implicated in the pathogenesis of cancer, which could contribute to therapeutic intervention in cancer.

Radical cross-coupling reactions represent a revolutionary tool to make C(sp3)–C and C(sp3)–heteroatom bonds by means of transition metals and photoredox or electrochemical approaches. However, the use of main-group elements to harness this type of reactivity has been little explored. Here we show how a low-valency bismuth complex is able to undergo one-electron oxidative addition with redox-active alkyl-radical precursors, mimicking the behaviour of first-row transition metals. This reactivity paradigm for bismuth gives rise to well-defined oxidative addition complexes, which could be fully characterized in solution and in the solid state. The resulting Bi(III)–C(sp3) intermediates display divergent reactivity patterns depending on the α-substituents of the alkyl fragment. Mechanistic investigations of this reactivity led to the development of a bismuth-catalysed C(sp3)–N cross-coupling reaction that operates under mild conditions and accommodates synthetically relevant NH-heterocycles as coupling partners.

The synthesis and redox reactivity of pentacoordinate phosphorus compounds incorporating a redox-active ONO amidodiphenoxide scaffold [ONO = N,N-bis(3,5-di-tert-butyl-2-phenoxide)amide] are described. Dichloro- and diphenylphosphoranes, 2·Cl and 2·Ph, respectively, are synthesized and crystallographically characterized. Cyclic voltammograms of 2·Cl show only a single irreversible oxidation (E = +0.83 V vs CpFe), while the diphenyl analogue 2·Ph is reversibly oxidized at lower applied potential (E = +0.47 V vs CpFe). Chemical oxidation of 2·Ph with AgBF produces the corresponding radical cation [2·Ph], where electron paramagnetic resonance spectroscopy and density functional theory calculations reveal that the unpaired spin density is largely ligand-based and is highly delocalized throughout the ONO framework of the paramagnetic species. The solid-state structures indicate only minor geometrical changes between the neutral 2·Ph and oxidized [2·Ph] species, consistent with fast self-exchange electron transfer, as observed by NMR line-broadening experiments.