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Synthesis of 3‐Borylated Pyrrolidines by 1,3‐Dipolar Cycloaddition of Alkenyl Boronates and Azomethine Ylide

2022; Wiley; Volume: 28; Issue: 54 Linguagem: Inglês

10.1002/chem.202202117

1521-3765

Oleksandr S. Liashuk, Ihor A. Ryzhov, Oleksandr V. Hryshchuk, Bohdan V. Vashchenko, Pavlo V. Melnychuk, Yulian M. Volovenko, Oleksandr O. Grygorenko,

Catalytic Cross-Coupling Reactions

A scalable and efficient process for the preparation of 3-borylated pyrrolidines by 1,3-dipolar cycloaddition of N-benzyl azomethine ylide generated in situ has been developed. The optimized method included the use of LiF in DMSO at 110 °C and was suitable for α-mono-, α,β-di-, and α,β,β-trialkyl-, β,β-(hetera)cycloalkylidene-, CO2 Et-, as well as most β-(het)aryl-substituted alkenyl boropinacolates. The 1,3-dipolar reaction proceeded on a multigram scale providing 3-borylated pyrrolidines with diverse substitution patterns (including fused and spirocyclic ones) in a diastereoselective manner. The Pd(OH)2 -mediated N-debenzylation of pyrrolidine hydrochlorides was successfully performed to give the corresponding bifunctional building blocks on an up to 130 g scale, thus providing a substantial expansion of the synthetic and medicinal chemist's toolbox. Other reactions included the preparation of trifluoroborates, Zweifel-Aggarwal sp3 -sp2 coupling, and oxidative deborylation as an example of C-heteroatom bond formation.