Synthesis of Fmoc-Protected Arylphenylalanines (Bip Derivatives) via Nonaqueous Suzuki-Miyaura Cross-Coupling Reactions

  • J Org Chem. 2016 Oct 7;81(19):9499-9506. doi: 10.1021/acs.joc.6b01965.
Jennifer X Qiao  1 ,  Kenneth J Fraunhoffer  1 ,  Yi Hsiao  1 ,  Yi-Xin Li  1 ,  Chunlei Wang  1 ,  Tammy C Wang  1 ,  Michael A Poss  1
Affiliations
  • 1. Discovery Chemistry, ‡Chemical and Synthetic Development, and §Pharmaceutical Candidate Optimization, Research and Development, Bristol-Myers Squibb Company , P.O. Box 4000, Princeton, New Jersey 08543-4000, United States.
PMID: 27615449 DOI: 10.1021/acs.joc.6b01965
Abstract

A one-step synthesis of Fmoc-protected aryl/heteroaryl-substituted phenylalanines (Bip derivatives) using the nonaqueous palladium-catalyzed Suzuki-Miyaura cross-coupling (SMC) reaction of Fmoc-protected bromo- or iodophenylalanines is reported. This protocol allows for the direct formation of a variety of unnatural biaryl-containing Amino acids in good to excellent yield, which can be readily used in subsequent Fmoc solid-phase peptide synthesis. The synthetic utility of this method is also demonstrated by the SMC reaction of bromophenylalanine-containing tripeptides.

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