Synthesis of Unnatural α-Amino Acids from (Pyridin-2-yl) Carbamate via CIPE-Induced Carbonyl Migration
Juhui Wang1, Aiwen Huo1, Xiang Li2
1State Key Laboratory of Metastable Materials Science and Technology, Hebei Key Laboratory of Nano-Biotechnology, Yanshan University, Qinhuangdao 066004, P. R. China.
Abstract:
Synthetic methods of unnatural α-amino acids have always been the focus of extensive research due to their significant bioactivities. However, convenient transition-metal-free catalyzed methods are still in demand. Herein, we report a novel strategy for the construction of an unnatural α-amino acid skeleton via intramolecular rearrangement of carbamates, which are readily available from amines and their common protecting groups. This rearrangement could afford a variety of amino ester products in up to 98% yield, even in gram-scale reaction. The reaction mechanism was studied in detail through experiments and theoretical calculations. The complex-induced proximity effect (CIPE) from the 2-pyridyl group is shown to be indispensable for this transformation.
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