posted on 1999-02-19, 00:00authored byJoseph M. Salvino, Miljenko Mervic, Helen J. Mason, Terence Kiesow, David Teager, John Airey, Richard Labaudiniere
This paper describes a novel supported Weinreb amide resin that facilitates parallel synthesis of
aldehydes and ketones on a scale useful for chemical library synthesis. This new resin makes it
possible to produce custom aldehydes and ketones from a wide range of carboxylic acids, including
N-BOC-amino acids. A variety of commercially unavailable aldehydes are easily synthesized in
parallel and obtained in high purity via a simple filtration workup, thus facilitating parallel
synthesis of lead optimization libraries that typically require custom synthesis of aldehyde
intermediates for development of structure−activity relationships. To demonstrate the utility of
this method, we synthesized a small library based on a supported Horner−Emmons reagent. This
is the first time it has been shown that aldehydes generated via a supported Weinreb amide could
be used directly as reagents in chemical library synthesis employing moisture-sensitive reactions.
The analogous solution reaction is not suited for parallel synthesis because of the laborious extractive
workup procedure necessary and, at times, the instability of these reactive intermediates.