Organocatalytic Enantioselective Conia-Ene-Type Carbocyclization of Ynamide Cyclohexanones: Regiodivergent Synthesis of Morphans and Normorphans

Yin Xu; Qing Sun; Tong-De Tan; Ming-Yang Yang; Peng Yuan; Shao-Qi Wu; Xin Lu; Xin Hong; Long-Wu Ye

doi:10.1002/anie.201908495

Organocatalytic Enantioselective Conia-Ene-Type Carbocyclization of Ynamide Cyclohexanones: Regiodivergent Synthesis of Morphans and Normorphans

Angew Chem Int Ed Engl. 2019 Nov 4;58(45):16252-16259. doi: 10.1002/anie.201908495. Epub 2019 Sep 18.

Authors

Yin Xu¹, Qing Sun², Tong-De Tan¹, Ming-Yang Yang¹, Peng Yuan¹, Shao-Qi Wu³, Xin Lu², Xin Hong³, Long-Wu Ye^{1

4}

Affiliations

¹ State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
² State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory for Theoretical and Computational Chemistry of Fujian Province, and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
³ Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
⁴ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China.

PMID: 31444882
DOI: 10.1002/anie.201908495

Abstract

Described herein is an organocatalytic enantioselective desymmetrizing cycloisomerization of arylsulfonyl-protected ynamide cyclohexanones, representing the first metal-free asymmetric Conia-ene-type carbocyclization. This method allows the highly efficient and atom-economical construction of a range of valuable morphans with wide substrate scope and excellent enantioselectivity (up to 97 % ee). In addition, such a cycloisomerization of alkylsulfonyl-protected ynamide cyclohexanones can lead to the divergent synthesis of normorphans as the main products with high enantioselectivity (up to 90 % ee). Moreover, theoretical calculations are employed to elucidate the origins of regioselectivity and enantioselectivity.

Keywords: asymmetric catalysis; cyclizations; desymmetrization; heterocycles; organocatalysis.

Publication types

Review
Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding