Herein, we report the redox-neutral allylation of aldehydes with readily available electron-rich allyl (hetero-) arenes, β-alkyl styrenes and allyl-diarylamines. This process was enabled by the combination of photoredox and chromium catalysis, which allowed a range of homoallylic alcohols to be prepared with high levels of selectivity for the anti diastereomer. Mechanistic investigations support the formation of an allyl chromium intermediate from allylic C(sp)-H bonds and thus significantly extends the scope of the venerable Nozaki-Hiyama-Kishi reaction.

The concept of reductive radical-polar crossover (RRPCO) reactions has recently emerged as a valuable and powerful tool to overcome limitations of both radical and traditional polar chemistry.

The discovery and application of dearomative cascade photocatalysis as a strategy in complex molecule synthesis is described. Visible-light-absorbing photosensitizers were used to (sequentially) activate a 1-naphthol derived arene precursor to divergently form two different polycyclic molecular scaffolds through catalyst selective energy transfer.

The direct conversion of feedstock chemicals into value-added products is of broad interest in chemical research. Herein, we present a regioselective and diastereoselective three-component dialkylation of feedstock 1,3-dienes with Hantzsch esters and aldehydes for the synthesis of homoallylic alcohols. The reaction is enabled by dual photoredox and chromium catalysis and can also be performed enantioselectively by employing chromium-bisoxazoline complexes.

Transition-metal-catalyzed allylic substitution is one of the most powerful and frequently used methods in organic synthesis. In particular, palladium-catalyzed allylic functionalization has become a well-established strategy to construct carbon-carbon or carbon-heteroatom bonds, and its utility has been demonstrated in natural product synthesis, drug discovery and materials science. Several methods have been developed to generate -allylpalladium complexes through ionic mechanisms; however, these methods typically require either prefunctionalized starting materials or stoichiometric oxidants, which naturally limits their scope. Here we show a radical approach for the generation of -allylpalladium complexes by employing N-hydroxyphthalimide esters as bifunctional reagents in combination with 1,3-dienes. Using this strategy, we report the 1,4-aminoalkylation of dienes. The remarkable scope and functional group tolerance of this redox-neutral and mild protocol was demonstrated across > 60 examples. The utility of this strategy was further demonstrated in radical cascade reactions and in the late-stage modification of drugs and natural products.

Developing efficient and selective strategies to approach complex architectures containing (multi)­stereogenic centers has been a long-standing synthetic challenge in both academia and industry. Catalytic cascade reactions represent a powerful means of rapidly leveraging molecular complexity from simple feedstocks. Unfortunately, carrying out cascade Heck-type reactions involving unactivated (tertiary) alkyl halides remains an unmet challenge owing to unavoidable β-hydride elimination. Herein, we show that a modular, practical, and general palladium-catalyzed, radical three-component coupling can indeed overcome the aforementioned limitations through an interrupted Heck/allylic substitution sequence mediated by visible light. Selective 1,4-difunctionalization of unactivated 1,3-dienes, such as butadiene, has been achieved by employing different commercially available nitrogen-, oxygen-, sulfur-, or carbon-based nucleophiles and unactivated alkyl bromides (>130 examples, mostly >95:5 E/Z, >20:1 rr). Sequential C­(sp3)–C­(sp3) and C–X (N, O, S) bonds have been constructed efficiently with a broad scope and high functional group tolerance. The flexibility and versatility of the strategy have been illustrated in a gram-scale reaction and streamlined syntheses of complex ether, sulfone, and tertiary amine products, some of which would be difficult to access via currently established methods.

Herein, we report the synthesis of protected 1,2-amino alcohols starting from carbonyl compounds and α-silyl amines. The reaction is enabled by a Cr/photoredox dual catalytic system that allows the in situ generation of α-amino carbanion equivalents which act as nucleophiles. The unique nature of this reaction was demonstrated through the aminoalkylation of ketones and an acyl silane, classes of electrophiles that were previously unreactive toward addition of alkyl-Cr reagents. Overall, this reaction broadens the scope of Cr-mediated carbonyl alkylations and discloses an underexplored retrosynthetic strategy for the synthesis of 1,2-amino alcohols.

The catalytic dearomatization of pyridines, accessing medicinally relevant N-heterocycles, is of high interest. Currently direct, dearomative strategies rely generally on reduction or nucleophilic addition, thus limiting the architecture of the dearomatized products to a six-membered ring. We herein introduce a catalytic, dearomative cycloaddition reaction with pyridines using photoinduced energy transfer catalysis, thereby advancing dearomatization methodology and increasing the topology of pyridine dearomatization products. This unprecedented method features high yields, broad substrate scope (44 examples), excellent functional group tolerance, and facile scalability. Furthermore, a recyclable and sustainable polymer immobilized photocatalyst was employed. Computational and experimental investigations support a mechanism in which a cinnamyl moiety is promoted to its corresponding excited triplet state through visible-light-mediated energy transfer catalysis, followed by a regioselective and dearomative [4+2] cycloaddition to pyridines. This work demonstrates the contribution of visible light catalysis toward enabling thermally challenging organic transformations.