ABSTRACT
Introduction e synthesis of large combinatorial libraries of low molecular weight, drug-like molecules requires robust chemistry employing a wide variety of diversity elements on solid support. e carboxylic acid functional group has been widely used in solid-phase chemistry, especially when protected as an ester. An allyl ester is a commonly used protecting group that can be used with many acid or base-labile linkers, and is removed easily with Pd(PPh3)4 in various solvent systems with the aid of a scavenger reagent [1-3]. Phenylsilane, acting as a hydride donor, has been reported to be an excellent scavenger when used in conjunction with Pd(PPh3)4 in the removal of the allyl ester group [4]. Recently, it was also reported from our laboratory that phenylsilane could be directly used as an active amidation reagent of carboxylic acids like other coupling agents [5]. Based on this nding, a novel, one-step to convert allyl ester to amide, using palladium and phenylsilane as activating agents, has been developed on solid support (Scheme 1). In an eort to explore the generality and scope of this method, this reaction was examined using various structurally diverse carboxylic acids and amines (primary, secondary, or anilines) on solid support. A general method to protect carboxylic acids with an allyl ester group on solid support is also reported.
