Towards α,α-disubstituted amino acids containing vicinal stereocenters via stereoselective transition-metal catalyzed allylation

Abstract

Designer amino acids find use across many scientific disciplines. The preparation of amino acids bearing acyclic vicinal stereocenters remains a challenge in synthesis. Herein, we highlight transition-metal catalyzed allylations for the stereoselective synthesis of disubstituted α-amino acid precursors bearing vicinal stereocenters. Allylation of azlactones, α-imino esters, and aldimine esters with dienes and allylic leaving groups are among the most common strategies. These developments provide context for our work featuring the asymmetric addition of α-nitroesters to alkynes.

Simplifying the Synthesis of Nonproteinogenic Amino Acids via Palladium-Catalyzed δ-Methyl C–H Olefination of Aliphatic Amines and Amino Acids

“…Although multicomponent or tandem reactions proceeding via highly reactive intermediates seem to be the most approachable route, often they suffer from multiple synthetic steps, low productivity, and poor stereoselectivity. In this context, transition metal-catalyzed C–H functionalization can offer a simple and straightforward solution. − Particularly, palladium-catalyzed α -, β -, and γ -C­( sp 3 )–H functionalizations of different proteinogenic αAAs have come up as a very powerful tool in the last 10 years. − Very recently, our group has explored arylation and borylation at the distal δ- position of leucine. In 2021, Carretero and co-workers also demonstrated δ-arylation of different γ-unblocked αAA derivatives using a sulfonamide linker …”

Palladium-Catalyzed Aerobic Oxidative Spirocyclization of Alkyl Amides with Maleimides via β-C(sp3)–H Activation

“…To deal with such challenges, directing group-assisted C­(sp 3 )–H bond activation and subsequent functionalization were explored. Over the years, many groups have extensively reported C­(sp 3 )–H functionalization reactions like arylation, halogenation, olefination, alkynylation, and annulation. − Therefore, in the view of the directing group-assisted C­(sp 3 )–H functionalization, aliphatic amides containing a sulfonamide moiety as an auxiliary were gradually explored by various groups. , …”