Esterification of Polystyrene Wang resin with 5-hexynoic acid; solid-supported ester alkyneSyntheticPage 88 (2001)
Submitted 17th Aug 2001, published 17th Aug 2001
A contribution from the Caddick Group, Sussex
Polystyrene Wang resin, Novabiochem, 0.77mmol/g
5-Hexynoic acid (Lancaster)
(HATU, Rapp Polymere)
Diisopropylethylamine (DIPEA, Hünig's base, any supplier)
N,N-dimethylformamide (anhydrous, Aldrich)
Add DIPEA (1.34 mL, 10 eq, 7.7 mmol) to 5-Hexynoic acid (0.435 mL, 3.85 mmol, 5eq) solution in 5 mL dry DMF then add HATU (1.46 g, 3.85 mmol, 5 eq) and allow to stand for about 10 mins to activate acid. Add to Wang resin (1.0 g, 0.77 mmol, 0.77 mmol/g, 1 eq) preswollen in minimum volume dry DMF (about 5-10 mL). Shake overnight at room temperature. Wash 4 x 20 mL each with DMF, DCM and Methanol Use 25 mL Alltech tube as reaction vessel. Yield typically quantitative.
This provides a means of attaching an isolated alkyne to a solid support and has been repeated about 6 times on scales of 200mg resin - 2g resin with no change in yield (as assessed in later steps - see below). We went on to use this acceptor in radical addition reactions as in lead reference below.
The use of HATU is probably not critical although it does give good yields. This is a general procedure for the coupling of a carboxylic acid to a p-hydroxybenzyl resin and works also for PEG-based resins such as Tentagel. HATU is not compatible with alpha,beta-unsaturated acids such as acrylic acid. Use DIC/catalytic DMAP instead and no organic base.
Yield can be assessed by cleaving off hexynoic acid with 95%(aq) TFA for about 2h, but in the lead reference below, loading was assumed to be quantitative and yields were assessed after reaction on the triple bond followed by cleavage.
Caddick, S.; Hamza, D.; Wadman, S.N. Tetrahedron Lett. 1999, 40, 7285-7288.
1. S.-S. Wang (1973) J. Am. Chem. Soc. 95 1328.
This page has been viewed approximately 291 times since records began.
Get CDX file (Choose "Open this file from its current location" TWICE)
SyntheticPagesTM are for use
exclusively by those with training and experience in synthetic chemistry. While contributors
are asked to identify hazards and to use methods designed to reduce risk, no formal hazard
or risk assessments are included, and these procedures must be conducted at one's own risk.
SyntheticPages, its editors, owners and associates do not warrant or guarantee the safety of
individuals using these procedures and hereby disclaim any liability for any injuries or damages
claimed to have resulted from or related in any way to the procedures herein. Copyright ©2005 Synthetic Pages
Comment on this page!
Registered users may add comments to other pages. If you have already registered, please
log in, otherwise you may
Back to List