Polytetrahydrofuran cross-linked polystyrene resins for solid-phase organic synthesis.
Currently, divinylbenzene cross-linked polystyrene (DVB-PS) is the polymer of choice for use in solid-phase organic synthesis (SPOS). While much research has been directed toward the optimization of linker groups for the attachment of compounds to the polymer, the development of new polymers themselves has been relatively neglected. In an attempt to overcome the shortcomings of DVB-PS and to develop new polymers with optimum properties for use in organic synthesis, we have prepared a series of polystyrene polymers that incorporate flexible polytetrahydrofuran (PTHF) based cross-linkers. The objective of incorporating PTHF into the polymers was to slightly increase the overall polarity of the polymer and thus render the resins more organic solvent-like. Since the degree to which a resin swells in and absorbs a particular solvent correlates to how well substrates attached to the polymer are solvated, we compared the swelling of our new resins to commercially available DVB-PS resins. In all cases, we found that our resins swelled to a much greater extent than do DVB-PS resins, and their use should therefore allow for SPOS reaction conditions that more closely mimic homogeneous solution-phase conditions. It was also found that the PTHF chain length of the cross-linker does not affect the level of swelling since all of our cross-linkers afford resins with comparable levels of increased swelling. Furthermore, we have examined the utility of our resins in directed ortho-metalation reactions and found that the increased swelling of our resins allows for isolation of reaction products in yields comparable to what is achieved using standard solution-phase conditions.
Toy
P H
PH
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Reger
T S
TS
Garibay
P
P
Garno
J C
JC
Malikayil
J A
JA
Liu
G
G
Janda
K D
KD
D020650:Combinatorial Chemistry Techniques; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D011137:Polystyrenes
D003432:Cross-Linking Reagents; D005663:Furans; D011137:Polystyrenes