Details

Autor(en) / Beteiligte

• Zhang, Benxiang
• He, Jiayan
• Gao, Yang
• Levy, Laura
• Oderinde, Martins S
• Palkowitz, Maximilian D
• Dhar, T G Murali
• Mandler, Michael D
• Collins, Michael R
• Schmitt, Daniel C
• Bolduc, Philippe N
• Chen, TeYu
• Clementson, Sebastian
• Petersen, Nadia Nasser
• Laudadio, Gabriele
• Bi, Cheng
• Kawamata, Yu
• Baran, Phil S

Titel

Complex molecule synthesis by electrocatalytic decarboxylative cross-coupling

Ist Teil von

• Nature (London), 2023-11, Vol.623 (7988), p.745-751

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Modern retrosynthetic analysis in organic chemistry is based on the principle of polar relationships between functional groups to guide the design of synthetic routes . This method, termed polar retrosynthetic analysis, assigns partial positive (electrophilic) or negative (nucleophilic) charges to constituent functional groups in complex molecules followed by disconnecting bonds between opposing charges . Although this approach forms the basis of undergraduate curriculum in organic chemistry and strategic applications of most synthetic methods , the implementation often requires a long list of ancillary considerations to mitigate chemoselectivity and oxidation state issues involving protecting groups and precise reaction choreography . Here we report a radical-based Ni/Ag-electrocatalytic cross-coupling of substituted carboxylic acids, thereby enabling an intuitive and modular approach to accessing complex molecular architectures. This new method relies on a key silver additive that forms an active Ag nanoparticle-coated electrode surface in situ along with carefully chosen ligands that modulate the reactivity of Ni. Through judicious choice of conditions and ligands, the cross-couplings can be rendered highly diastereoselective. To demonstrate the simplifying power of these reactions, concise syntheses of 14 natural products and two medicinally relevant molecules were completed.