Imine Additions of Internal Alkynes for the Synthesis of Trisubstituted (E)‐Alkene and Cyclopropane Peptide Isosteres

Abstract

AbstractDivergent multi‐component reactions (DMCR) involving CC bond formations can provide large increases in structural diversity and allow the rapid assembly of complex products from readily available starting materials. Cascade hydrozirconation‐Zr/Zn transmetalation‐imine addition of alkynes represents a versatile methodology for the synthesis of (E)‐alkene and cyclopropane dipeptide isosteres. Appropriate substitutions at the sp2‐carbon of (E)‐alkene peptide isosteres allow a range of Pd‐catalyzed cross‐coupling reactions, which can be used for the fine‐tuning of the conformational and electronic properties of the parent peptide bond mimic. CC bond formation by microwave‐accelerated Stille coupling of stannylalkenes represents a fast, convergent synthetic approach toward trisubstituted (E)‐alkene dipeptide isosteres.