Soluble supports tailored for organic synthesis:: Parallel polymer synthesis via sequential normal/living free radical processes

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), H-1 and C-13 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 a-nitrile groups of polyBS-DS are reduced smoothly with LiAlH4 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 (k(poly22) = 0.49 L mol(-1) h(-1) vs k(aminohexane) = 0.69 L mol(-1) h(-1)). Following reaction of poly22 with N-glutaroyl-(2S,4S)-4-diphenylphosphino-2- [(diphenylphosphino)methyl] pyrrolidine (26) and exchange of Rh(I), the resulting phosphine containing copolymer Rh(I)-27, catalyzes the enantioselective hydrogenation of 2-N-aacetamidoacrylic 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.