Synthesis of N-Acylsulfenamides from Amides and N-Thiosuccinimides.

Herein is reported a robust and general method for the preparation of N-acylsulfenamides, important functionalities that have recently been utilized as central inputs for the asymmetric synthesis of high oxidation state sulfur compounds. This straightforward transformation proceeds by reaction of primary amides, carbamates, sulfonamides, sulfinamides, and ureas with stable N-thiosuccinimides or N-thiophthalimides, which in turn are prepared in a single step from commercial thiols. The use of stable N-thiosuccinimide and N-thiophthalimide reactants is desirable because it obviates the use of highly reactive sulfenyl chlorides.

Visible Light-Mediated, Highly Diastereoselective Epimerization of Lactams from the Most Accessible to the More Stable Stereoisomer.

Most known methods to access δ-lactams with stereogenic centers at the α- and ß-positions are highly selective for the contra-thermodynamic syn diastereomer, typically via hydrogenation of the corresponding pyridinones or quinolinones. We describe here the development of a photoredox-mediated hydrogen atom transfer (HAT) approach for the epimerization of δ-lactams to access the more stable anti diastereomers from the contra-thermodynamic syn isomers. The reaction displays broad functional group compatibility, including acid, ester, 1°, 2° and 3° amide, carbamate, and pyridyl groups, and was effective for a range of differently substituted monocyclic and bicyclic lactams. Experimentally observed diastereoselectivities are consistent with the calculated relative stabilities of lactam diastereomers. Convergence to the same diastereomer ratio from the syn- and anti- diastereomers establishes that reversible epimerization provides an equilibrium mixture of diastereomers. Additionally, deuterium labeling and luminescence quenching studies shed further light on the mechanism of the reaction.

C-H bond activation and sequential addition to two different coupling partners: a versatile approach to molecular complexity.

Sequential multicomponent C-H bond addition is a powerful approach for the rapid, modular generation of molecular complexity in a single reaction. In this approach, C-H bonds are typically added across π-bonds or π-bond isosteres, followed by subsequent coupling to another type of functionality, thereby forming two σ-bonds in a single reaction sequence. Many sequential C-H bond addition reactions have been developed to date, including additions across both conjugated and isolated π-systems followed by coupling with reactants such as carbonyl compounds, cyanating reagents, aminating reagents, halogenating reagents, oxygenating reagents, and alkylating reagents. These atom-economical reactions transform ubiquitous C-H bonds under mild conditions to more complex structures with a high level of regiochemical and stereochemical control. Surprising connectivities and diverse mechanisms have been elucidated in the development of these reactions. Given the large number of possible combinations of coupling partners, there are enormous opportunities for the discovery of new sequential C-H bond addition reactions.

Synthesis of α-Branched Amines by Three- and Four-Component C-H Functionalization Employing a Readily Diversifiable Hydrazone Directing Group.

Efficient syntheses of α-branched amines by three- and four-component C-H functionalization employing a diversifiable hydrazone directing group have been developed. The hydrazone in the α-branched amine products has been readily converted to multiple desirable functionalities such as a nitrile, a carboxylic acid, alkenes, and heterocycles using diverse heterolytic chemistry and homolytic transition metal- or photoredox-catalyzed processes. This study represents the first example of a four-component C-H functionalization reaction.

Three-Component 1,2-Carboamidation of Bridged Bicyclic Alkenes via RhIII-Catalyzed Addition of C-H Bonds and Amidating Reagents.

A three-component method is described for the preparation of syn-1,2-disubstituted bridged bicyclic compounds. The reaction was demonstrated for readily available aromatic and heteroaromatic C-H bond substrates with tertiary and secondary amide, lactam, pyrazole, and triazole directing groups and a variety of bridged bicyclic alkenes, including norbornene, benzonorbornadiene, oxygen- and nitrogen-bridged analogs, and an unsaturated tropinone. A broad dioxazolone scope was also observed. The use of a chiral Cp-derived RhIII catalyst enables asymmetric synthesis of products.