American Chemical Society
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Parallel Synthesis of Aldehydes and Ketone Facilitated by a New Solid-Phase Weinreb Amide

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journal contribution
posted on 1999-02-19, 00:00 authored by Joseph 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.