Silyl imine electrophiles in enantioselective catalysis: a Rosetta Stone for peptide homologation, enabling diverse N-protected aryl glycines from aldehydes in three steps.
We report that N-(trimethylsilyl)imines serve in the Bis(AMidine)-catalyzed addition of bromonitromethane with a high degree of enantioselection. This allows for the production of a range of protected α-bromo nitroalkane donors (including Fmoc) for use in Umpolung Amide Synthesis (UmAS). Hence, peptide homologation with nonnatural aryl glycine amino acids is achieved in three steps from aromatic aldehydes, which are plentiful and inexpensive. Epimerization during the homologation step is circumvented by avoiding an α-amino acid intermediate.
Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University , Nashville, Tennessee 37235, United States.
Dawn M
DM
Makley
Jeffrey N
JN
Johnston
D000447:Aldehydes / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D004980:Ethane / Q000031:analogs & derivatives / Q000737:chemistry; D005998:Glycine / Q000737:chemistry*; D009574:Nitro Compounds / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D017655:Silicon Compounds / Q000737:chemistry*
D000447:Aldehydes; D000596:Amino Acids; D009574:Nitro Compounds; D010455:Peptides; D017655:Silicon Compounds; C533588:bromonitromethane; D004980:Ethane; D005998:Glycine