Organocatalytic asymmetric synthesis of bioactive hexahydropyrrolo[2,3-b]indole-containing tetrasubstituted allenes bearing multiple chiral elements

Tetrahedron Chem

Wei Tan¹  Shuming Zhang²  Shu Zhang²  Xian-Yang Yu³  Hong-Lin Wan³  Jing-Yi Wang³  Yu-Hao Wang³  Feng Shi³ 

[1] Corresponding author.;Department of Gerontology, Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China;School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, China;

关键词: Asymmetric organocatalysis;    Axial chirality;    Catalytic asymmetric dearomatization;    para-quinone methides;    Chiral phosphoric acid;   

DOI  :  

来源: DOAJ

【 摘 要 】

An organocatalytic asymmetric construction of hexahydropyrrolo[2,3-b]indole-containing tetrasubstituted allene scaffolds bearing both axial chirality and central chirality has been established via a cascade 1,8-addition/dearomatization-cyclization reaction of para-aminophenyl propargylic alcohols with tryptamines in the presence of chiral phosphoric acid (CPA), thus affording a wide range of such tetrasubstituted allenes bearing multiple chiral elements in generally good yields (up to 94%) with high diastereo- and enantioselectivities (up to 95:5 dr, 95% ee). In addition, the evaluation on the cytotoxicity of some selected products indicated that this class of chiral tetrasubstituted allenes could inhibit the growth of the pancreatic cancer cells to some extent. This work not only solved the challenging issues in enantioselective construction of tetrasubstituted allenes via alkynyl (aza)-para-quinone methides, but also represents the first example of using alkyne derivatives as electrophiles in organocatalytic asymmetric dearomatizations of tryptamines.

【 授权许可】

Unknown