New Research Achieves Highly Enantioselective Synthesis of Tertiary 2-Amidoallylic Alcohols

ON2019-06-14TAG: ShanghaiTech UniversityCATEGORY: School of Physical Science and Technology

Recently, SPST Yang Xiaoyu’s group have achieved highly enantioselective synthesis of tertiary 2-amidoallylic alcohols, and their research was published in Angewandte Chemie International Edition with the title of “Kinetic Resolution of Tertiary 2-Alkoxycarboxamido-allylic Alcohols by Chiral Phosphoric Acid Catalyzed Intramolecular Transesterification.”

Chiral alcohols are important building blocks in synthesis of pharmaceuticals and bioactive natural products. The kinetic resolution of alcohols (including enzymatic and nonenzymatic catalysis process) is one of the most reliable and practical methods of obtaining enantiomeric pure alcohols. However, despite the fact that a lot of elegant methods have been developed for kinetic resolution of secondary alcohols, highly efficient kinetic resolution of tertiary alcohols remains one of the challenges in this field.

In 2018, Yang Xiaoyu’s group developed regio- and enantioselective addition of indoles to 2-amido cyclopentenols enabled by chiral phosphoric acid (Angew. Chem. Int. Ed. 2018, 57, 13489). With their continuous interest, they recently discovered that, with 2-alkoxycarboxamido substituted allylic alcohol as substrate, a highly efficient kinetic resolution of the tertiary alcohols was achieved via intramolecular transesterification under the catalysis of chiral phosphoric acid catalyst, with selectivity factor up to 164.6. A gram-scale reaction was performed to demonstrate the practicability of this reaction and the facile transformation of the chiral products into useful chiral building blocks proved the potential of this reaction in the synthesis of chiral drug molecules and natural products.   

Postdoc Subramani Rajkumar and joint graduate student He Shunlong are co-first authors of this article. Assistant Professor Yang Xiaoyu is the corresponding author and ShanghaiTech University is the first responsible institution.This work is supported by National Natural Science Foundation of China, “Pujiang Program” and ShanghaiTech University.

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Highly Efficient Kinetic Resolution of 2-Amidoallylic Alcohols