Lu(OTf) 3 ‐Catalyzed Ring‐Opening Polymerization of Sarcosine N ‐Carboxyanhydride with Quantitative Initiation Efficiency of Hydroxyl Groups

ABSTRACT It is promising but challenging to prepare poly(amino acid)s that directly bond to alcohols, especially saccharides. Herein, we report a novel method for the controlled ring‐opening polymerization (ROP) of sarcosine N ‐carboxyanhydride (Sar‐NCA) quantitatively initiated by hydroxyl groups using lutetium triflate (Lu(OTf) 3 ) as catalyst. Lu(OTf) 3 is devised to slow down the propagation by reducing the nucleophilicity of the amino group on the propagating chain end, thus realizing quantitative initiation efficiency (IE) of alcohol. Polysarcosine (PSar) samples with controlled molecular weights ( M n = 2.2–12.7 kg/mol) and low dispersities ( Đ = 1.11–1.15) are obtained and full IE of the hydroxyl group is realized. Kinetic studies reveal that the propagation rate of Sar‐NCA is significantly decreased in the presence of Lu(OTf) 3 . The addition of Lu(OTf) 3 converts the characteristic of alcohol‐initiated ROP of Sar‐NCA from “slow initiation and fast propagation” to “fast initiation and slow propagation” which is essential of the polymerization control. Density functional theory (DFT) calculations provide mechanistic insights that Lu(OTf) 3 is prone to coordinate with the propagating chain end species of secondary amino and carbamate groups in the form of five‐ or eight‐membered rings and retards the propagation. PSar products bearing glucose or mannose ester end groups, analogs of glycoproteins, are successfully synthesized by applying this protocol. The obtained mannose‐functionalized PSar shows significantly accelerated ingestion by cancer cells.