Dual Sequence Control of Uniform Macromolecules through Consecutive Single Addition by Selective Passerini Reaction

Abstract

The selective Passerini reactions of 4-formylbenzoic acid and 4-isocyanobenzoic acid with aliphatic isocyanides and aldehydes were utilized to synthesize sequence-defined uniform macromolecules. Our strategy does not involve any protecting groups or reactive group transformation steps and allows direct and consecutive propagation of sequence in each step. Introduction of diverse side groups by using different aliphatic components provided a range of sequence-defined uniform macromolecules in high yield and gram scale. The strategy also allows further Passerini self-coupling or cross-coupling of the formed sequences with other small molecules, affording polymers with up to 5098.3 Da and 20 side groups. Thus, this strategy will show promise for more efficient synthesis of new sequence-defined macromolecules.

Discrete and Stereospecific Oligomers Prepared by Sequential and Alternating Single Unit Monomer Insertion

“…[19][20][21] Various strategies have been proposed for regulating monomer sequence and chain length of synthetic polymers, including condensation chain polymerization, 22 alternating radical polymerization, [23][24][25][26][27][28][29] anionic polymerization, [30][31] ring-opening or cross metathesis polymerization, [32][33][34] atom transfer radical addition (ATRA), [24][25][35][36][37] iterative exponential growth, [38][39][40][41][42][43] single unit monomer insertion 12,[44][45][46][47][48][49][50] and various organic coupling, condensation or "click" addition reactions. 19,[51][52][53][54][55][56][57][58][59][60][61][62]…”

Multicomponent Reactions and Multicomponent Cascade Reactions for the Synthesis of Sequence‐Controlled Polymers

“…Very recently, Li et al. reported selective coupling approach toward sequence control of monodisperse oligomers by Passerini reaction ( Figure ) . Chemoselectivity of aliphatic aldehyde and aliphatic isocyanide groups was identified and introduced in sequence control.…”

“…C) Structure and synthetic routes toward sequence‐defined oligomers. Reproduced with permission . Copyright 2017, American Chemical Society.…”

Upscaling single unit monomer insertion to synthesize discrete oligomers

“…Motivated by the desire to prepare such precise structures, an increasing number of innovative physical and chemical approaches have been developed during the past decades, including automated separation system, atom transfer radical addition, click‐based chemistry (thio‐ene, thio‐maleimide, and thiolactone), phosphoramidite chemistry, multicomponent reaction, photo‐ligation chemistry, and ionic polymerization techniques . Most of the elegant examples in these approaches use an iterative exponential growth (IEG) process, which evolves from step‐growth polymerization and uses pre‐protected bifunctional monomers to achieve sequential attachments and doubles the molecular weights of synthetic oligomers/polymers . As a recent example, the IEG plus side‐chain functionalization (IEG+) protocol proposed by Johnson and coworkers provided control on both sequence and stereochemistry at the same time.…”