Stereocontrolled Synthesis of Adjacent Acyclic Quaternary-Tertiary Motifs: Application to a Concise Total Synthesis of (−)-Filiformin

• Published in: Angewandte Chemie International Edition 2014-05, Vol.53 (22), p.5552-5555
• Main Authors: Blair, Daniel J., Fletcher, Catherine J., Wheelhouse, Katherine M. P., Aggarwal, Varinder K.
• Format: Article
• Language: English
• Subjects: boron; Boronic Acids - chemistry; Bromobenzenes - chemical synthesis; Bromobenzenes - chemistry; Carbamates - chemistry; enantioselectivity; Esters; Isomers; lithium; Lithium - chemistry; Methodology; natural products; Stereochemistry; Stereoisomerism; Synthesis; total synthesis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201400944

Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary‐tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel‐type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps have been applied to the shortest enantioselective synthesis of (−)‐filiformin to date (9 steps) with full stereocontrol. True to (fili)form: Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary‐tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel‐type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps were applied to the enantioselective synthesis of (−)‐filiformin.