Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to N-Unprotected Ketimines: Efficient Synthesis of Cipargamin

Jinbin Zhu; Linwei Huang; Wei Dong; Naikai Li; Xingxin Yu; Wei-Ping Deng; Wenjun Tang

doi:10.1002/anie.201910008

Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to N-Unprotected Ketimines: Efficient Synthesis of Cipargamin

Angew Chem Int Ed Engl. 2019 Nov 4;58(45):16119-16123. doi: 10.1002/anie.201910008. Epub 2019 Sep 24.

Authors

Jinbin Zhu¹, Linwei Huang¹, Wei Dong², Naikai Li², Xingxin Yu¹, Wei-Ping Deng^{1

2}, Wenjun Tang^{1

2}

Affiliations

¹ Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Rd, Shanghai, 200237, China.
² State Key Laboratory of Bio-Organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling Ling Rd, Shanghai, 200032, China.

PMID: 31468680
DOI: 10.1002/anie.201910008

Abstract

Highly enantioselective rhodium-catalyzed addition of arylboroxines to N-unprotected ketimines is realized for the first time by employing chiral BIBOP-type ligands with a Rh loading as low as 1 mol %. A range of chiral α-trifluoromethyl-α,α-diaryl α-tertiary amines or 3-amino-3-aryloxindoles were formed with excellent ee values and yields by employing either WingPhos or PFBO-BIBOP as the ligand. The method has enabled an efficient enantioselective synthesis of cipargamin.

Keywords: P ligands; asymmetric catalysis; enantioselectivity; ketimines; rhodium.

Abstract

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