A Ni/photoredox dual catalytic cross-coupling is disclosed in which a diverse range of (hetero)aryl bromides are used as electrophiles, with 1,4-dihydropyridines serving as precursors to Csp3-centered alkyl radical coupling partners. The reported method is characterized by its extremely mild reaction conditions, enabling access to underexplored cores.

A mechanistically distinct, Ni/photoredox-catalyzed arylation of unprotected, native thiols (e.g., cysteine residues) is reported – a process initiated through a visible light-promoted, hydrogen atom transfer (HAT) event under ambient conditions.

Carbon dioxide exhibits many of the qualities of an ideal reagent – it is nontoxic, plentiful, and inexpensive. Unlike other gaseous reagents, however, it has found limited use in enantioselective synthesis. Moreover, unprecedented is a tool that merges one of the simplest biological approaches to catalysis – Brønsted acid/base activation – with this abundant reagent. We describe a metal-free small molecule catalyst that achieves the three component reaction between a homoallylic alcohol, carbon dioxide, and an electrophilic source of iodine. Cyclic carbonates are formed enantioselectively.

Alkyl xanthate esters are perhaps best known for their use in deoxygenation chemistry. However, their use in cross-coupling chemistry has not been productive, which is due, in part, to inadequate xanthate activation strategies. Herein, we report the use of O-benzyl xanthate esters, readily derived from alcohols, as radical pronucleophiles in Csp3–Csp2 cross-couplings under Ni/photoredox dual catalysis. Xanthate (C–O) cleavage is found to be reliant on photogenerated (sec-butyl) radical activators to form new carbon-centered radicals primed for nickel-catalyzed cross-couplings. Mechanistic experiments support the fact that the key radical components are formed independently, and relative rates are carefully orchestrated, such that no cross reactivity is observed.

The finding by scientists at Hoffmann-La Roche that cis-imidazolines could disrupt the protein–protein interaction between p53 and MDM2, thereby inducing apoptosis in cancer cells, raised considerable interest in this scaffold over the past decade. Initial routes to these small molecules (i.e., Nutlin-3) provided only the racemic form, with enantiomers being enriched by chromatographic separation using high-pressure liquid chromatography (HPLC) and a chiral stationary phase. Reported here is the first application of an enantioselective aza-Henry approach to nonsymmetric cis-stilbene diamines and cis-imidazolines. Two novel mono(amidine) organocatalysts (MAM) were discovered to provide high levels of enantioselection (>95% ee) across a broad range of substrate combinations. Furthermore, the versatility of the aza-Henry strategy for preparing nonsymmetric cis-imidazolines is illustrated by a comparison of the roles of aryl nitromethane and aryl aldimine in the key step, which revealed unique substrate electronic effects providing direction for aza-Henry substrate–catalyst matching. This method was used to prepare highly substituted cis-4,5-diaryl imidazolines that project unique aromatic rings, and these were evaluated for MDM2-p53 inhibition in a fluorescence polarization assay. The diversification of access to cis-stilbene diamine-derived imidazolines provided by this platform should streamline their further development as chemical tools for disrupting protein–protein interactions.