RESUMO
The merging of photoredox and nickel catalysis has revolutionized the field of C-C cross-coupling. However, in comparison to the development of synthetic methods, detailed mechanistic investigations of these catalytic systems are lagging. To improve the mechanistic understanding, computational tools have emerged as powerful tools to elucidate the factors controlling reactivity and selectivity in these complex catalytic transformations. Based on the reported computational studies, it appears that the mechanistic picture of catalytic systems is not generally applicable, but is rather dependent on the specific choice of substrate, ligands, photocatalysts, etc. Given the complexity of these systems, the need for more accurate computational methods, readily available and user-friendly dynamics simulation tools, and data-driven approaches is clear in order to understand at the molecular level the mechanisms of these transformations. In particular, we anticipate that such improvement of theoretical methods will become crucial to advance the understanding of excited-state properties and dynamics of key species, as well as to enable faster and unbiased exploration of reaction pathways. Further, with greater collaboration between computational, experimental, and spectroscopic communities, the mechanistic investigation of photoredox/Ni dual-catalytic reactions is expected to thrive quickly, facilitating the design of novel catalytic systems and promoting our understanding of the reaction selectivity.
RESUMO
Herein we report a workflow coupling photoredox-nickel dual-catalyzed N-arylation reactions to benchtop analysis for the efficient generation of fragment-based libraries. Technological advances in photoreactor design facilitated reliable and reproducible experimentation. Knowledge on the reactivity under previously reported reaction conditions of spirocyclic and strained heterocyclic building blocks, viewed as chemistry informers, could thus be rapidly accessed, identifying privileged or challenging scaffolds and paving the way for further exploration.
RESUMO
Herein, the introduction of oxa- and azabenzonorbornadienes into photoredox/nickel dual catalysis in a regioselective and diastereoselective transformation is disclosed. The inherent advantages of this dual catalytic system allow the use of alkyl motifs forming exclusively cis-1,2-dihydro-1-naphthyl alcohol backbones using readily accessible 4-alkyl-1,4-dihydropyridines (DHPs). Whereas previous studies have emphasized the use of nucleophilic organometallic coupling partners, this protocol grants access to a rather unexplored core featuring alkyl residues, while avoiding the use of highly reactive organometallic species (i.e., M = Al, Mg, Li, Zn, Zr). DFT calculations support a oxidative addition/reductive elimination mechanism, followed by a Curtin-Hammett scenario that controls the regioselectivity of the process, unlike previously reported transformations that proceed via a carbometalation/ ß-oxygen elimination mechanism.
RESUMO
Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode for transmetalation of sp(3)-hybridized organoboron reagents enables C-C bond formation in the presence of various protected and unprotected sp(2)-hybridized organoborons. This manifold has the potential for broad application, because orthogonality is inherent to the activation mode itself. The diversification potential of this platform is shown in the rapid elaboration of a trifunctional lynchpin through various transition metal-catalyzed processes without nonproductive deprotection or functional group manipulation steps.
