Stereoselective Organocatalyzed Synthesis of α-Fluorinated β-Amino Thioesters and Their Application in Peptide Synthesis.

Angew Chem Int Ed Engl

ETH Zürich, Laboratory for Organic Chemistry, D-CHAB, Vladimir-Prelog-Weg 1-5/10, 8093, Zürich, Switzerland.

Published: October 2016

α-Fluorinated β-amino thioesters were obtained in high yields and stereoselectivities by organocatalyzed addition reactions of α-fluorinated monothiomalonates (F-MTMs) to N-Cbz- and N-Boc-protected imines. The transformation requires catalyst loadings of only 1 mol % and proceeds under mild reaction conditions. The obtained addition products were readily used for coupling-reagent-free peptide synthesis in solution and on solid phase. The α-fluoro-β-(carb)amido moiety showed distinct conformational preferences, as determined by crystal structure and NMR spectroscopic analysis.

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http://dx.doi.org/10.1002/anie.201607146DOI Listing

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