Total Synthesis of Rameswaralide

• Applicant: Dr. Daniel Zell
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398264478

• Final Report Year: 2019

Final Report Abstract

The synthesis of chiral from racemic allenes constitutes a challenge in organic chemistry and the corresponding synthetic methods have been limited to kinetic resolutions of racemic allenes. In contrast, our methodology1 allows for the synthesis of structurally complex chiral allenes from readily available racemic allenes by palladium-catalysis. The reaction proceeds via a catalyst-controlled generation of a diastereomeric palladium/nucleophile complex and its addition to activated achiral electrophiles. That leads to absolute control of stereochemistry and substitution around the allene core with excellent levels of regio-, diastereo-, and enantiocontrol. Furthermore, we were able to demonstrate the involvement of a DYKAT process and a stepwise mechanism for the cycloaddition event. The densely functionalized chiral allenes were readily derivatized to a variety of useful molecules in a particularly step-economic manner.

Publications

• Enantio‐and Diastereoselective Synthesis of Chiral Allenes by Palladium ‐Catalyzed Asymmetric [3+ 2] Cycloaddition Reactions, Angew. Chem. Int. Ed. 2018, 57, 12916–12920
  B. M. Trost, D. Zell, C. Hohn, G. Mata, A. Maruniak
  
• Palladium-Catalyzed Asymmetric Allylic Fluoroalkylation/Trifluoromethylation, J. Am. Chem. Soc. 2019, 141, 11446–11451
  B. M. Trost, H. Gholami, D. Zell