Soluble Supports Tailored for Organic Synthesis: Parallel Polymer SynthesisviaSequential 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), 1 H and 13 C NMR, and as a function of the solubility of each polymer in a range of solvents. One copolymer, poly BS-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 α-nitrile groups of poly BS-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 ( k poly 22 = 0.49 L mol - 1 h - 1 vs k aminohexane = 0.69 L mol - 1 h - 1 ). Following reaction of poly 22 with N -glutaroyl-(2 S,4 S )-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 -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.