Modular Synthesis of Congested b2,2-Amino Acids via the Merger of Photocatalysis and Oxidative Functionalisations

b-Amino acids are privileged scaffolds present in numerous bioactive compounds, as well as versatile synthons in organic chemistry. b2- or b3-amino acids can be readily synthesised, however, access to b2,2-analogues is limited by challenges associated with building the quaternary centre. Herein, we report a two-step protocol for the modular synthesis of b2- and -quaternary b2,2-amino acid derivatives from readily available feedstocks such as carbonyl compounds, malononitrile, and -amino acids. The key steps are: 1) a photocatalytic decarboxylative radical hydroalkylation reaction that enables the facile construction of the a-quaternary centre, and 2) an oxidative esterification converting the malononitrile motif into the targeted ester moiety. This versatile approach grants selective access to b-amino esters, b-amino amides, or N-protected b-amino acids bearing bulky substituents on the a-position. Additionally, we demonstrated that this synthesis can be effectively scaled up via continuous-flow technology.