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Journal Article

trans-Hydrogenation: Application to a Concise and Scalable Synthesis of Brefeldin A

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons145352

Fuchs,  Michael
Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons58380

Fürstner,  Alois
Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

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Citation

Fuchs, M., & Fürstner, A. (2015). trans-Hydrogenation: Application to a Concise and Scalable Synthesis of Brefeldin A. Angewandte Chemie International Edition, 54(13), 3978-3982. doi:10.1002/anie.201411618.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0025-AE5F-A
Abstract
The important biochemical probe molecule brefeldin A (1) has served as an inspirational target in the past, but none of the many routes has actually delivered more than just a few milligrams of product, where documented. The approach described herein is clearly more efficient; it hinges upon the first implementation of ruthenium-catalyzed trans-hydrogenation in natural products total synthesis. Because this unorthodox reaction is selective for the triple bond and does not touch the transannular alkene or the lactone site of the cycloalkyne, it outperforms the classical Birch-type reduction that could not be applied at such a late stage. Other key steps en route to 1 comprise an iron-catalyzed reductive formation of a non-terminal alkyne, an asymmetric propiolate carbonyl addition mediated by a bulky amino alcohol, and a macrocyclization by ring-closing alkyne metathesis catalyzed by a molybdenum alkylidyne.