Soluble Supports Tailored for Organic Synthesis:  Parallel Polymer SynthesisviaSequential Normal/Living Free Radical Processes

Abstract

To expand the availability and solubility range of polymer supports for liquid-phase organic synthesis (LPOS) we have applied a sequence of normal and "living" free radical polymerization to generate a library of block copolymers possessing either block or graft architecture with initiators 1-4 and a diverse set of vinyl monomers 5-9. The structure, molecular weight, and polydispersity (PD) of the individual library members have been determined by size exclusion chromatography (SEC), 1 H and 13 C NMR, and as a function of the solubility of each polymer in a range of solvents. One copolymer, polyBS-DS (M n ) 17 000, PD ) 1.54) derived from 4-tert-butylstyrene (6, BS), 3,4-dimethoxystyrene (7, DS), and initiator 1 has a solubility profile [soluble in toluene, tetrahydrofuran (THF), ether, acetone and methylene chloride (DCM), insoluble in methanol and water] that is different from the present polymer of choice for LPOS, poly(ethylene) glycol (PEG), and has been studied in some detail as a new support in LPOS. The R-nitrile groups of polyBS-DS are reduced smoothly with LiAlH 4 in THF to give the amino functionalized copolymer 22 (0.14 mmol g -1 of amino groups based on a quantitative ninhydrin analysis). Kinetic studies have revealed that derivatization of the amino groups of 22 with 4-dimethylaminocinnamaldehyde 23 occurs at a comparable rate to a solution counterpart 26) and exchange of Rh(I), the resulting phosphine containing copolymer Rh(I)-27, catalyzes the enantioselective hydrogenation of 2-N-acetamidoacrylic acid (28) to N-acetylalanine (29) in THF. An 87% enantiomeric excess (ee) of (S)-29 is obtained, comparable to that observed with a homogeneous phosphine ligand. This work highlights the power of a parallel polymer synthesis strategy, from conception to application, for the generation of polymers possessing unique solubility profiles and functionality which can serve as novel supports in LPOS.

Investigation of soluble PEG-imidazoles as the thermal latency catalysts for epoxy-phenolic resins

“…The soluble polymer-supported synthesis [23] of small organic molecules is a subject of intense research activity due to their profit from both the advantageous features of homogeneous solution chemistry (high reactivity, lack of diffusion phenomena, analytical simplicity) and of solid-phase methods (ready isolation and easy purification 1. n =~2 (PEG200-Im), 2. n =~6 (PEG400-Im)…”

Automated Parallel Synthesis of MADIX (Co)Polymers

“…Automated parallel controlled radical polymerizations, [17] like nitroxide-mediated polymerization (NMP), [5,18,19] atom transfer radical polymerization (ATRP), [20,21] and RAFT Communication: An automated parallel synthetic approach has been developed for synthesizing polymer libraries by the Macromolecular Design via the Interchange of Xanthates (MADIX) process. The experimental set-up, parallel polymerizations, characterization, and reproducibility tests are detailed.…”

Combinatorial Methods, Automated Synthesis and High‐Throughput Screening in Polymer Research: Past and Present

“…The resulting size distribution of the polymer beads was reproducible and showed that this parallel approach is useful for the rapid design of polymeric bead supports and to optimize polymerization conditions. A manual parallel free-radical polymerization approach towards new soluble supports for organic synthesis has been described by Janda et al [48] Bifunctional initiators with both an a-nitrilediazene (-N N-) and a 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) group were utilized to synthesize block copolymers, whereby five different monomers were utilized. The a-nitrilediazene was first polymerized at 70 8C with different monomers.…”