Organocatalytic atroposelective construction of axially chiral N, N- and N, S-1,2-azoles through novel ring formation approach.

Yu Chang, Chuandong Xie, Hong Liu, Shengli Huang, Pengfei Wang, Wenling Qin, Hailong Yan

Nature communications 2022 Apr 11

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1,2-Azoles are privileged structures in ligand/catalyst design and widely exist in many important natural products and drugs. In this report, two types of axially chiral 1,2-azoles (naphthyl-isothiazole S-oxides with a stereogenic sulfur center and atropoisomeric naphthyl pyrazoles) are synthesized via modified vinylidene ortho-quinone methide intermediates. Diverse products are acquired in satisfying yields and good to excellent enantioselectivities. The vinylidene ortho-quinone methide intermediates bearing two hetero atoms at 5-position have been demonstrated as a platform molecule for the atroposelective synthesis of axially chiral 1,2-azoles. This finding not only enrich our knowledge of vinylidene ortho-quinone methide chemistry but also provide the easy preparation method for diverse atropisomeric heterobiaryls that were inaccessible by existing methodologies. The obtained chiral naphthyl-isothiazole S-oxides and naphthyl-pyrazoles have demonstrated their potential application in further synthetic transformations and therapeutic agents. © 2022. The Author(s).

Citation

Yu Chang, Chuandong Xie, Hong Liu, Shengli Huang, Pengfei Wang, Wenling Qin, Hailong Yan. Organocatalytic atroposelective construction of axially chiral N, N- and N, S-1,2-azoles through novel ring formation approach. Nature communications. 2022 Apr 11;13(1):1933