Fast and selective organocatalytic ring-opening polymerization by fluorinated alcohol without a cocatalyst

Abstract

Organocatalysis is an important branch of catalysis for various organic transformations and materials preparation. Polymerizations promoted by organic catalysts can produce polymeric materials without any metallic residues, providing charming materials for high-value and sensitive domains such as biomedical applications, microelectronic devices and food packaging. Herein, we describe a fluorinated alcohol based catalytic system for polypeptide synthesis via catalytic ring-opening polymerization (ROP) of α -amino acid N -carboxyanhydride (NCA), fulfilling cocatalyst free, metal free, high rate and high selectivity. During polymerization, the fluorinated alcohol catalyst forms multiple dynamic hydrogen bonds with the initiator, monomer and propagating polymer chain. These cooperative hydrogen bonding interactions activate the NCA monomers and simultaneously protect the overactive initiator/propagating polymer chain-ends, which offers the whole polymerization with high activity and selectivity. Mechanistic studies indicate a monocomponent-multifunctional catalytic mode of fluorinated alcohol. This finding provides a metal free and fast approach to access well-defined polypeptides.

Accelerated polymerization of N-carboxyanhydrides catalyzed by crown ether

“…The fast polymerization kinetics outpaces various side reactions, enabling the polymerization in the presence of moisture and even aqueous phase 21 , 25 , 27 – 29 . Well-defined polypeptides with complex structures 19 , 20 , 23 , high MWs 20 , 22 , 26 , and unique block sequences 27 were therefore synthesized in an efficient manner, which is difficult, if not impossible, with conventional NCA ROP methods.…”

A Synthetic Method for Site‐Specific Functionalized Polypeptides: Metal‐Free, Highly Active, and Selective at Room Temperature

“…In our pursuit of exploring highly active and selective metal‐free catalytic systems for polypeptide synthesis, [29, 35, 36] we found that organic hydrogen‐bonding donors, such as thiourea and fluorinated alcohol, could function as efficient organocatalysts for the ROP of N ‐carboxyanhydride (NCA) [35, 36] . In contrast to the bicomponent–bifunctional catalytic systems (thiourea/R 3 N) for ROPs of cyclic esters, the hydrogen‐bonding donor, thiourea or fluorinated alcohol, can catalyze ROP of NCAs in the absence of cocatalysts (usually weak bases), demonstrating an unconventional monocomponent–multifunctional catalytic mode.…”

“…Despite the excellent control over molecular weights and molecular weight distributions, the polymerization rates are usually slow. Thanks to the continuous contributions and efforts of researchers over the last few years, this situation has been improved and several new initiating systems such as allied amines, [29] N ‐trimethylsilyl amines, [30] sulfur–tin Lewis pair, [31] N ‐heterocyclic carbenes(NHCs), [32] aliphatic diamines, [33] and lithium hexamethyldisilazide, [34] and new organocatalytic systems based on organic hydrogen‐bonding donors [35, 36] were successively reported for ROP of NCAs with high polymerization selectivities and fast kinetics, which greatly facilitated the access of polypeptide materials. However, few of these new systems have been explored for the synthesis of functionalized polypeptides.…”

Accelerated Polypeptide Synthesis via N‐Carboxyanhydride Ring Opening Polymerization in Continuous Flow

“…[ 32 ] Hadjichristidis and co‐workers recently reported a substantial increase in polymerization rate afforded by the use of a fluorinated alcohol catalyst in chlorinated solvents. [ 33 ] The organocatalyst was found to form multiple cooperative hydrogen bonds, activating the NCA monomers and simultaneously protecting the initiator/growing polymer chain ends, resulting in a polymerization with high activity and selectivity. These recent advances in NCA ring opening polymerization provide an exciting variety of options to access polypeptides with increased speed for a plethora of applications.…”