Ketone-Olefin Coupling of Aliphatic and Aromatic Carbonyls Catalyzed by Excited-State Acridine Radicals.

Ketone-olefin coupling reactions are common methods for the formation of carbon-carbon bonds. This reaction class typically requires stoichiometric or super stoichiometric quantities of metal reductants, and catalytic variations are limited in application. Photoredox catalysis has offered an alternative method toward ketone-olefin coupling reactions, although most methods are limited in scope to easily reducible aromatic carbonyl compounds. Herein, we describe a mild, metal-free ketone-olefin coupling reaction using an excited-state acridine radical super reductant as a photoredox catalyst. We demonstrate both intramolecular and intermolecular ketone-olefin couplings of aliphatic and aromatic ketones and aldehydes. Mechanistic evidence is also presented supporting an "olefin first" ketone-olefin coupling mechanism.

Deoxy-Arylation of Amides via a Tandem Hydrosilylation/Radical- Radical Coupling Sequence.

Vaska's complex is a prominent catalyst for the hydrosilylation of amides. The O-silyl hemiaminal intermediate formed in these processes has been demonstrated as an electrophile for nucleophilic additions. More recently, these intermediates have been shown to be suitable for single electron reduction to generate α-amino radicals. Leveraging the ability to generate α-amino radicals from these hemiaminals, we describe a two-step, one-pot, deoxy-arylation of amides utilizing iridium-catalyzed hydrosilylation and photoredox catalysis. This transformation can be tailored toward the late-stage functionalization of biologically relevant molecules, with drug discovery applications as shown in the streamlined synthesis of an NPY Y2 inhibitor.

Photoredox-Catalyzed Multicomponent Synthesis of Functionalized γ-Amino Butyric Acids via Reductive Radical Polar Crossover.

Multicomponent radical polar crossover (RPC) reactions are useful for leveraging both radical and polar bond-forming steps to rapidly build molecular complexity in a single transformation. However, multicomponent RPC reactions that utilize carbonyl π-bond electrophiles are underrepresented in the literature. Herein, we describe a mild, photoredox-catalyzed decarboxylative multicomponent RPC reaction that couples carboxylic acids, Michael acceptors, and carbonyl electrophiles for the formation of diversely functionalized γ-amino butyric acid derivatives. This transformation also facilitates the synthesis of complex and biologically relevant γ-lactam compounds.

Cation Radical-Accelerated Nucleophilic Aromatic Substitution for Amination of Alkoxyarenes.

Nucleophilic aromatic substitution (SNAr) is a common method for arene functionalization; however, reactions of this type are typically limited to electron-deficient aromatic halides. Herein, we describe a mild, metal-free, cation-radical accelerated nucleophilic aromatic substitution (CRA-SNAr) using a potent, highly oxidizing acridinium photoredox catalyst. Selective substitution of arene C-O bonds on a wide array of aryl ether substrates was shown with a variety of primary amine nucleophiles. Mechanistic evidence is also presented that supports the proposed CRA-SNAr pathway.

Nondirected, Cu-Catalyzed sp3 C-H Aminations with Hydroxylamine-Based Amination Reagents: Catalytic and Mechanistic Studies.

This work demonstrates the use of hydroxylamine-based amination reagents RSO2NH-OAc for the nondirected, Cu-catalyzed amination of benzylic C-H bonds. The amination reagents can be prepared on a gram scale, are benchtop stable, and provide benzylic C-H amination products with up to 86% yield. Mechanistic studies of the established reactivity with toluene as substrate reveal a ligand-promoted, Cu-catalyzed mechanism proceeding through Ph-CH2(NTsOAc) as a major intermediate. Stoichiometric reactivity of Ph-CH2(NTsOAc) to produce Ph-CH2-NHTs suggests a two-cycle, radical pathway for C-H amination, in which the decomposition of the employed diimine ligands plays an important role.