Asymmetric synthesis of tetrazole and dihydroisoquinoline derivatives by isocyanide-based multicomponent reactions

• Published in: Nature communications Vol. 10; no. 1; pp. 2116 - 10
• Main Authors: Xiong, Qian, Dong, Shunxi, Chen, Yushuang, Liu, Xiaohua, Feng, Xiaoming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.05.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 140/58; 639/638/549/933; 639/638/549/972; 639/638/77/883; Alkylidene; Asymmetric synthesis; Catalysis; Chemical reactions; Derivatives; Dipoles; Enantiomers; Heterocyclic compounds; Humanities and Social Sciences; Hypotheses; Investigations; Ligands; multidisciplinary; Nitrogen; Optical activity; Organic chemistry; Science; Science (multidisciplinary); Tetrazoles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09904-5

Although isocyanide-based multicomponent reactions were proven to be simple, elegant and facile strategies for the synthesis of highly valuable nitrogen-containing heterocycles, their asymmetric versions accessing to optically active nitrogen heterocyclic compounds are rather limited. Here, we illustrate that, relying on the enantioselective addition of simple isocyanides to C=C bonds, several isocyanide-based multicomponent reactions are realized in the presence of a chiral Mg II - N , N ʹ-dioxide catalyst. In the reaction among isocyanide, TMSN 3 , and alkylidene malonate, three- or four-component reactions could be precisely controlled by modulating reaction conditions, supplying two types of enantioenriched tetrazole-derivatives in moderate to high yields. Possible catalytic cycles via a key zwitterionic intermediate, and the vital roles of H 2 O or excess ligand are provided based on control experiments. Moreover, taking advantage of this zwitterionic intermediate as a 1,3-dipole, an enantioselective dearomative [3+2] annulation reaction of nonactivated isoquinolines is achieved, furnishing chiral 1,2-dihydroisoquinolines in good to excellent results. Asymmetric isocyanide-based multicomponent reactions are elegant, yet challenging, strategies to access valuable N-heterocycles. Here, the authors employ a chiral Mg(II) -N,N′-dioxide catalyst in three- or four-component reactions to obtain chiral tetrazoles and devise a dearomative [3+2] annulation reaction of isoquinolines.