A general and practical cross-dehydrogenative coupling protocol between readily available trisubstituted α,β-dehydro α-amino carboxylic esters and H-phosphites is described. This C­(sp2)–H phosphorylation reaction proceeds with absolute Z-selectivity promoted by silver salt in a radical relay manner. The bulky tetrasubstituted β-phosphonodehydroamino acids were obtained in grams and added new modules to the toolkit for peptide modifications.

Chiral amino acids featuring a phosphonate pendant arm are an important type of biologically active scaffold. Here in this review, we comprehensively summarize the modern synthetic methods towards asymmetric construction of chiral amino carboxylic‐phosphonic acid derivatives. The main streams of such interesting compounds include phosphono‐containing α‐, β‐, and γ‐amino acid derivatives, amino acid fluorophosphonate derivatives, amino acid cyclopropanylphosphonate derivatives, and bisphosphono‐amino acid derivatives. Chiral resolution protocols, chiral auxiliary‐directed syntheses, and valorization of the pool of abundant chiral amino acid resources remain contemporary concerns, and meanwhile catalytic enantioselective synthesis has also emerged as a potent strategy as demonstrated by the latest advances.magnified image

Alkyl N-aryl 1,2,3-triazole-carboxylates are important molecules or intermediates in medicinal chemistry, but the synthesis of N 2-aryl counterparts remains elusive. Herein, we describe a Cu-mediated annulation reaction of alkyl 3-aminoacrylates with aryldiazonium salts, both of which are readily available substrates. Furthermore, alkyl 2-aminoacrylates are also viable substrates. Diverse alkyl N 2-aryl 1,2,3-triazole-carboxylates and their analogues can be rapidly prepared under mild conditions. Especially, this protocol allows one to access several druglike variants of carbonic anhydrase inhibitors and celecoxib.

Organophosphorus compounds are essential structures in modern pharmaceutical, agrochemical, and material sciences. The development of new and efficient methods for the synthesis of C–P bonds has been an important focus of research. We herein report a Pd‐catalyzed enamido C(sp2)–H phosphorylation for direct construction of C–P bonds under simple and convenient conditions without the need for additional ligands or directing groups. The present reaction can tolerate a wide range of functional groups, and furnish a variety of phosphorylation products including tetrasubstituted‐vinyl β‐aminophosphonates that are otherwise difficult to access. This protocol was also exemplified into the late‐stage modification of bioactive natural products and was suitable for large‐scale synthesis.