Selective Cleavage of Lignin Model Compounds via a Reverse Biosynthesis Mechanism.

Selective depolymerization of lignin remains a significant challenge in biomass conversion. The biosynthesis of lignin involves the polymerization of monolignol building blocks through oxidative radical coupling reactions. A strategy for lignin degradation leverages photoredox deoxygenative radical formation to trigger reverse biosynthesis, which cleaves model compounds of the ß-O-4 and ß-5-ß-O-4 linkages to produce monolignols, precursors to flavoring compounds. This mild method preserves important oxygen functionality and serves as a platform for achieving selective lignin depolymerization.

Late-Stage Modification of Oligopeptides by Nickel-Catalyzed Stereoselective Radical Addition to Dehydroalanine.

Radical addition to dehydroalanine (Dha) represents an appealing, modular strategy to access non-canonical peptide analogues for drug discovery. Prior studies on radical addition to the Dha residue of peptides and proteins have demonstrated outstanding functional group compatibility, but the lack of stereoselectivity has limited the synthetic utility of this approach. Herein, we address this challenge by employing chiral nickel catalysts to control the stereoselectivity of radical addition to Dha on oligopeptides. The conditions accommodate a variety of primary and secondary electrophiles to introduce polyethylene glycol, biotin, halo-tag, and hydrophobic and hydrophilic side chains to the peptide. The reaction features catalyst control to largely override substrate-based control of stereochemical outcome for modification of short peptides. We anticipate that the discovery of chiral nickel complexes that confer catalyst control will allow rapid, late-stage modification of peptides featuring nonnatural sidechains.

Rh(III)-Catalyzed Selective Olefination of N-Carboxamide Indoles with Unactivated Olefins at Room Temperature via an Internal Oxidation.

A mild, convenient, and effective Rh(III)-catalyzed site-selective C2-alkenylation of N-carboxamide indoles with unactivated alkenes at room temperature via an internal oxidation is described. The present olefination reaction was well-studied with plentiful indole N-carboxamides as well as unfunctionalized/functionalized unactivated alkenes. In this reaction, the directing group containing N-OMe acts as an internal oxidant. A possible reaction mechanism involving C-H activation/insertion/internal oxidation followed by protonation is proposed and supported by the deuterium-labeling studies.

Aerobic Oxidative C-H Olefination of Arylamides with Unactivated Olefins via a Rh(III)-Catalyzed C-H Activation.

An efficient Rh(III)-catalyzed aerobic oxidative C-H alkenylation of arylamides with unactivated alkenes is described. The olefination reaction was compatible with various substituted arylamides including primary, secondary, and tertiary as well as functionalized unactivated olefins. Meanwhile, ortho mono/bis-alkylated arylamides were synthesized in the reaction of arylamides with norbornene. In the alkenylation reaction, molecular oxygen along with organic acid was used to regenerate the active catalyst for the next catalytic cycle. A possible reaction mechanism involving C-H activation/insertion/ß-hydride elimination followed by aerobic oxidation was proposed and supported by the deuterium labeling studies.

Rhodium(III)-Catalyzed C-H Olefination of Aromatic/Vinyl Acids with Unactivated Olefins at Room Temperature.

A Rh(III)-catalyzed COOH-assisted C-H alkenylation of aromatic acids with unactivated alkenes at room temperature is described. Further, the highly challenging ß-C-H olefination of acrylic acids with unactivated olefins was also demonstrated. In these reactions, ortho-alkenylated aromatic/vinylic acids were prepared in good to excellent yields. A possible reaction mechanism involving ortho C-H activation and a five-membered rhodacycle formation was proposed and supported by the deuterium-labeling studies and isolation of a key rhodacycle intermediate.

Rhodium(III)-Catalyzed Redox-Neutral Weak O-Coordinating Vinylation and Allylation of Arylacetamides with Allylic Acetates.

An efficient Rh(III)-catalyzed redox-neutral weak O-coordinating vinylation and allylation of arylacetamides with allylic acetates are described. A wide variety of arylacetamides containing primary, secondary, and tertiary amides and substituted allylic acetates was compatible for the reaction. The synthesized ortho-vinylated arylacetamides were converted into ortho-vinylated phenyl acetic acid and biologically useful 3-isochromanones. A possible reaction mechanism involving π-allyl rhodium intermediate was suggested and further confirmed through deuterium labeling studies.

Ruthenium(II)-Catalyzed Distal Weak O-Coordinating C-H Alkylation of Arylacetamides with Alkenes: Combined Experimental and DFT Studies.

The C-H alkylation of arylacetamides with activated alkenes such as substituted acrylates and vinyl sulphone in the presence of a ruthenium catalyst and organic acid via the weak O-coordination under the redox free version is described. The present protocol was effective with different substituted arylacetamides including secondary and tertiary amides. The reaction mechanism including the ortho C-H bond activation, migratory insertion, and protonation by acetic acid was suggested and supported by the deuterium labeling experiments, competitive experiments, and DFT calculations including TS analysis.

Aerobic Oxidative Alkenylation of Weak O-Coordinating Arylacetamides with Alkenes via a Rh(III)-Catalyzed C-H Activation.

A versatile and site-selective rhodium(III)-catalyzed aerobic oxidative alkenylation of arylacetamides including primary, secondary, and tertiary amides having a weak O-coordinating acetamide directing group with alkenes is described. In the reaction, air was utilized as a sole oxidant. The reaction was compatible with activated alkenes and maleimides.

Ruthenium(II)-Catalyzed Cyclization of Aromatic Acids with Allylic Acetates via Redox-Free Two-Fold Aromatic/Allylic C-H Activations: Combined Experimental and DFT Studies.

A Ru(II)-catalyzed, redox-free, two-fold aromatic/allylic C-H bond activation of aromatic acids with allylic acetates to give ( Z)-3-ylidenephthalides is described. In the reaction, H2 was formed as a side product. The detailed mechanistic investigation and DFT studies including the transition-state analysis support the postulate that the C-H allylation takes place at the ortho position of aromatic acids with allylic acetates followed by intramolecular cyclization at the allylic C(sp3)-H via a π-allylruthenium intermediate.