title: Parallel Synthesis of Aldehydes and Ketone Facilitated by a New Solid-Phase Weinreb Amide.
abstract: 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.
authors.affiliation: Lead Discovery Department, Rhone-Poulenc Rorer, 500 Arcola Road, Collegeville, Pennsylvania 19426.
authors.forename: Joseph M.
authors.initials: JM
authors.lastname: Salvino
authors.forename: Miljenko
authors.initials: M
authors.lastname: Mervic
authors.forename: Helen J.
authors.initials: HJ
authors.lastname: Mason
authors.forename: Terence
authors.initials: T
authors.lastname: Kiesow
authors.forename: David
authors.initials: D
authors.lastname: Teager
authors.forename: John
authors.initials: J
authors.lastname: Airey
authors.forename: Richard
authors.initials: R
authors.lastname: Labaudiniere