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Stereocontrolled Total Synthesis of (-)-Stemaphylline.

ABSTRACT: Homologation of readily available ?-boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl^- ) are employed. By performing a solvent switch from Et₂ O to CHCl₃ , efficient 1,2-metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (-)-stemaphylline in just 11 steps (longest linear sequence), with high stereocontrol (>20:1 d.r.) and 11?% overall yield. The synthesis also features a late-stage lithiation-borylation reaction with a tertiary amine containing carbenoid.

SUBMITTER: Varela A

PROVIDER: S-EPMC5484348 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Stereocontrolled Total Synthesis of (-)-Stemaphylline.

Varela Ana A Garve Lennart K B LK Leonori Daniele D Aggarwal Varinder K VK

Angewandte Chemie (International ed. in English) 20170118 8

Homologation of readily available α-boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl- ) are employed. By performing a solvent switch from Et2 O to CHCl3 , efficient 1,2-metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (-)-stemaphylline in just 11 steps (longest linear sequence), with high ...[more]

PMID: 28097799

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