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. 2021 Aug;33(8):465-478.
doi: 10.1002/chir.23320. Epub 2021 May 26.

FAM-Ag-catalyzed asymmetric synthesis of heteroaryl-substituted pyrrolidines

Nurzhan Beksultanova  1 , Zeynep Gözükara  1 , Mihrimah Araz  1 , Merve Bulut  1 , Sıdıka Polat-Çakır  2 , Muhittin Aygün  3 , Özdemir Dogan  1
Affiliations

FAM-Ag-catalyzed asymmetric synthesis of heteroaryl-substituted pyrrolidines

Nurzhan Beksultanova et al. Chirality. 2021 Aug.

Abstract

New derivatives of FAM (ferrocenyl aziridinyl methanol) ligands NFAM1-4 (naphthyl ferrocenyl aziridinyl methanol) and CFAM1-4 (cyclohexyl ferrocenyl aziridinyl methanol) were synthesized to form a small ligand library and used as chiral catalysts with AgOAc for the asymmetric synthesis of heteroaryl-substituted pyrrolidines by the 1,3-dipolar cycloaddition (1,3-DC) reaction of azomethine ylides. 2-Thienyl, 2-furyl, 2-, 3-, and 4-pyridyl aldimines were prepared and used with N-methylmaleimide, dimethyl maleate, tert-butyl acrylate, methyl acrylate, and acrylonitrile to form the corresponding heteroaryl-substituted pyrrolidines. 1,3-DC reactions yielded the expected cycloadducts in up to 89% yield and up to 76% ee that could be increased up to 95% ee upon crystallization. New chiral ligands NFAM1-4 and CFAM1-4 were fully characterized, and their absolute stereochemistry was determined by single-crystal X-ray analysis.

Keywords: asymmetric synthesis; chiral FAM ligands; chiral metal catalyst; heteroaryl-substituted pyrrolidines.

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References

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