Differing from the moisture-sensitive alpha-amino acid N-carboxyanhydrides (AA-NCAs) monomers, N-phenoxycarbonyl alpha-amino acids (AA-NPCs) can be prepared and stored in open air. In this contribution, we report that the controlled polymerizations of AA-NPC monomers of O-tert-butyl-dl-serine (BRS-NPC), N-epsilon-benzyloxycarbonyl-l-lysine (ZLL-NPC) and N-epsilon-trifluoroacetyl-l-lysine (FLL-NPC) initiated by amines are surprisingly able to tolerate common nucleophilic impurities such as water and alcohols at a level of monomer concentration. The structures of polypeptides synthesized in the presence of water or alcohols agree well with the designed ones in the case of repeated chain extensions. Detailed mechanism study and density functional theory calculation reveal that the low concentration of AA-NCA and the high activity of amines are the key factors to the controllability of AA-NPC polymerizations. The water- and alcohol-tolerant property in polymerizations of AA-NPCs encourages the following studies on unprotected (phenolic) hydroxyl groups containing AA-NPCs. The controllable polymerizations of N-phenoxycarbonyl l-tyrosine (LT-NPC) and N-phenoxycarbonyl S-(3-hydroxypropyl)-l-cysteine (HLC-NPC) initiated by amines are confirmed and reported for the first time, which extends the library of AA-NPCs and polypeptides as well. All the universality of library, the convenience of monomer preparation, and the controllability and water- and alcohol-tolerant property of polymerization of AA-NPCs significantly enhance the feasibility of polypeptide synthesis, making AA-NPC approach a promising synthetic method of polypeptides. (c) 2019 Wiley Periodicals, Inc.