Atroposelective synthesis ofN-aryl peptoid atropisomersviaa palladium(ii)-catalyzed asymmetric C-H alkynylation strategy

Abstract

The introduction of chirality into peptoids is an important strategy to determine a discrete and robust secondary structure. However, the lack of an efficient strategy for the synthesis of structurally diverse chiral peptoids has hampered the studies. Herein, we report the efficient synthesis of a wide variety ofN-aryl peptoid atropisomers in good yields with excellent enantioselectivities (up to 99% yield and 99% ee) by palladium-catalyzed asymmetric C-H alkynylation. The inexpensive and commercially availablel-pyroglutamic acid was used as an efficient chiral ligand. The exceptional compatibility of the C-H alkynylation with various peptoid oligomers renders this procedure valuable for peptoid modifications. Computational studies suggested that the amino acid ligand distortion controls the enantioselectivity in the Pd/l-pGlu-catalyzed C-H bond activation step.