Modular synthesis of congested ß2,2-amino acids via the merger of photocatalysis and oxidative functionalisations.

A two-step protocol for the modular synthesis of ß2- and α-quaternary ß2,2-amino acid derivatives is reported. The key steps are a photocatalytic hydroalkylation reaction, followed by an oxidative functionalisation to access N-protected ß-amino acids, esters, and amides. This strategy can be effectively scaled up via continuous-flow technology.

Modular Synthesis of Polar Spirocyclic Scaffolds Enabled by Radical Chemistry.

Herein, we report a highly modular strategy to access spirocyclic scaffolds from abundant starting materials, i.e., cyclic ketones and α-amino or oxamic acids. The sequence proceeds through a straightforward Knoevenagel condensation, followed by a domino Giese-type reaction/base-mediated cyclization process, to deliver a broad scope of polar spirocyclic scaffolds in good to excellent yields. The products can be readily diversified, thus increasing the versatility of our method to gain rapid access to libraries of potential druglike molecules.

Synthesis of γ-Oxo-α-amino Acids via Radical Acylation with Carboxylic Acids.

Herein we present a highly efficient, light-mediated, deoxygenative protocol to access γ-oxo-α-amino acid derivatives. This radical methodology employs photoredox catalysis, in combination with triphenylphosphine, to generate acyl radicals from readily available (hetero)aromatic and vinylic carboxylic acids. This approach allows for the straightforward synthesis of γ-oxo-α-amino acids bearing a wide range of functional groups (e.g., Cl, CN, furan, thiophene, Bpin) in synthetically useful yields (∼60% average yield). To further highlight the utility of the methodology, several deprotection and derivatization reactions were carried out.

Radical-Based Synthesis and Modification of Amino Acids.

Amino acids (AAs) are key structural motifs with widespread applications in organic synthesis, biochemistry, and material sciences. Recently, with the development of milder and more versatile radical-based procedures, the use of strategies relying on radical chemistry for the synthesis and modification of AAs has gained increased attention, as they allow rapid access to libraries of novel unnatural AAs containing a wide range of structural motifs. In this Minireview, we provide a broad overview of the advancements made in this field during the last decade, focusing on methods for the de novo synthesis of α-, ß-, and γ-AAs, as well as for the selective derivatisation of canonical and non-canonical α-AAs.