Bond cleavage, fragment modification and reassembly in enantioselective three-component reactions

• Published in: Nature communications Vol. 6; no. 1; p. 5801
• Main Authors: Zhang, Dan, Zhou, Jun, Xia, Fei, Kang, Zhenghui, Hu, Wenhao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.01.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 639/638/403/934; 639/638/403/935; 639/638/77; Humanities and Social Sciences; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6801

Chemical bond cleavage and reconstruction are common processes in traditional rearrangement reactions. In contrast, the process that involves bond cleavage, fragment modification and then reconstruction of the modified fragment provides an efficient way to build structurally diversified molecules. Here, we report a palladium(II)/chiral phosphoric acid catalysed three-component reaction of aryldiazoacetates, enamines and imines to afford α-amino-δ-oxo pentanoic acid derivatives in good yields with excellent diastereoselectivities and high enantioselectivities. The stereoselective reaction went through a unique process that involves cleavage of a C–N bond, modification of the resulting amino fragment and selective reassembly of the modified fragment. This innovative multi-component process represents a highly efficient way to build structurally diversified polyfunctional molecules in an atom and step economic fashion. A keto-iminium is proposed as a key intermediate and a chiral palladium/phosphate complex is proposed as an active catalyst. Multi-component reactions allow complex structures to be rapidly built from simple starting materials. Here, the authors report an enantioselective three-component coupling of imines, enamines and aryldiazoacetates catalysed by a phosphinic acid and palladium(II).