Silver-catalysed double decarboxylative addition-cyclisation-elimination cascade sequence for the synthesis of quinolin-2-ones.

An atom-efficient silver-catalysed double carboxylative strategy for the one-step synthesis of quinolin-2-ones via an addition-cyclisation-elimination cascade sequence of oxamic acids to acrylic acids, mediated either thermally or photochemically, is reported. The reaction was applicable to the synthesis of a broad range of quinolin-2-ones and featured a double-disconnection approach that constructed the quinolin-2-one core via the formal and direct addition of a C(sp2)-H/C(sp2)-H olefin moiety to a phenylformamide precursor.

Visible-Light-Mediated Energy Transfer Enables the Synthesis of ß-Lactams via Intramolecular Hydrogen Atom Transfer.

The synthesis of 2-azetidinones (ß-lactams) from simple acrylamide starting materials by visible-light-mediated energy transfer catalysis is reported. The reaction features a C(sp3 )-H functionalization via a variation of the Norrish-Yang photocyclization involving a carbon-to-carbon 1,5-hydrogen atom transfer (supported by deuterium labelling and DFT calculations) and can be used for the construction of a diverse range of ß-lactam products.

Low-Temperature, Transition-Metal-Free Cross-Dehydrogenative Coupling Protocol for the Synthesis of 3,3-Disubstituted Oxindoles.

A new low-temperature procedure for the synthesis of 3,3-disubstituted 2-oxindoles via cross-dehydrogenative coupling (CDC) is reported. The use of a strong, nonreversible base in these reactions has been found to effect a dramatic drop in reaction temperature (to room temperature) relative to the current state-of-the-art (>100 °C) procedure. When employing iodine as an "oxidant", new evidence suggests that this transformation may occur via a transiently stable iodinated intermediate rather than by direct single-electron oxidation.

Quaternized α,α'-Amino Acids via Curtius Rearrangement of Substituted Malonate-Imidazolidinones.

An efficient synthesis protocol is presented for accessing quaternized α-amino acids in chiral, nonracemic form via diastereoselective malonate alkylation followed by C- to N-transposition. The key stereodifferentiating step involves a diastereoselective alkylation of an α-monosubstituted malonate-imidazolidinone, which is followed first by a chemoselective malonate PMB ester removal and then a Curtius rearrangement to provide the transposition. The method demonstrates a high product ee (89-99% for eight cases) for quaternizing a range of proteinogenic α-amino acids. The stereogenicity in targets 5a-i supports previous conclusions that the diastereoselective alkylation step proceeds via an α-substituted malonate-imidazolidinone enolate in its Z-configuration, with the auxiliary in an s-transC-N conformation.

Photoredox-catalyzed procedure for carbamoyl radical generation: 3,4-dihydroquinolin-2-one and quinolin-2-one synthesis.

A reductive approach for carbamoyl radical generation from N-hydroxyphthalimido oxamides under photoredox catalysis is outlined. This strategy was applied to the synthesis of 3,4-dihydroquinolin-2-ones via the intermolecular addition/cyclization of carbamoyl radicals with electron deficient olefins in a mild, redox-neutral manner. Under a general set of reaction conditions, diversely substituted 3,4-dihydroquinolin-2-ones, including spirocyclic systems can be prepared. By using chlorine-substituted olefins, aromatic quinolin-2-ones can also be accessed.

Cross-Dehydrogenative Cyclization-Dimerization Cascade Sequence for the Synthesis of Symmetrical 3,3'-Bisoxindoles.

The synthesis of symmetrical 3,3'-bisoxindoles from simple acyclic ß-oxoanilides is reported. The described method forges three new C-C bonds in a single step via a sequential Mn(OAc)3·2H2O mediated oxidative radical cyclization-fragmentation-dimerization process. The scope of this reaction is demonstrated in the preparation of a variety of 3,3'-bisoxindoles, as well as its application toward the formal synthesis of the Calycanthaceae alkaloid, (±)-folicanthine.

Visible-Light Mediated Metal-Free 6π-Photocyclization of N-Acrylamides: Thioxanthone Triplet Energy Transfer Enables the Synthesis of 3,4-Dihydroquinolin-2-ones.

An efficient thioxanthone-catalyzed triplet energy transfer process for the synthesis of 3,4-dihydroquinolin-2-ones via a 6π-photocyclization is reported. Featuring a rare example of a metal-free formal C(sp2)-H/C(sp3)-H arylation mediated by visible-light, this work hopes to inspire further interest in these small molecules as sustainable alternatives to existing transition-metal photocatalysts in related processes.

Photoredox-Catalyzed Reductive Carbamoyl Radical Generation: A Redox-Neutral Intermolecular Addition-Cyclization Approach to Functionalized 3,4-Dihydroquinolin-2-ones.

The first reductive generation of carbamoyl radicals using photoredox catalysis for their formation is reported. This approach facilitated the development of a redox-neutral synthesis of functionalized 3,4-dihydroquinolin-2-ones via the novel intermolecular addition-cyclization of carbamoyl radicals across electron-deficient alkenes. To illustrate the versatility of this reaction, a diverse collection of 3,4-dihydroquinolin-2-ones, including fused cyclic and spirocyclic systems inspired by natural products, has been prepared.