Timothy Mcallister

First examples of a tosylate in the palladium-catalyzed Heck cross coupling reaction

Abstract The palladium-catalyzed cross coupling Heck reaction of tosylate ( 2 ) and methyl acrylate has been developed as an efficient method for carboncarbon bond formation. The tosylate ( 2 ) was reacted with methyl acrylate using palladium acetate as catalyst to provide 3-(3-oxo-1-cyclohexen-1-yl)-2-propenoic acid methyl ester ( 3 ) in excellent yield. The coupling reaction of tosylate ( 9 ) under the similar conditions also provided the dienoic acid methyl ester ( 10 ) in >80% overall yield. The effect of reaction parameters such as temperature and catalyst as well as the ratio of palladium acetate to triphenylphosphine on the reaction rate has been studied.

Process for preparing Ezetimibe intermediate by an acid enhanced chemo- and enantioselective CBS catalyzed ketone reduction

The S alcohol in the benzylic position of compound 2, a key feature of a novel cholesterol lowering agent Ezetimibe, was introduced by the (R)-MeCBS catalyzed asymmetric carbonyl reduction of ketone 1 using borane tetrahydrofuran complex (BTHF) as the reducing agent. The chemo- and enantioselectivity was dramatically enhanced by using an acid as a scavenger of the stabilizer sodium borohydride present in the commercially supplied pure BTHF. The effect of the critical reaction parameters such as addition mode of reagent, temperature, acids as well as water content on the selectivity has been examined. This reaction has been successfully applied in the commercial process for the preparation of the key intermediate 2 for Ezetimibe.

A SHORT AND CONVENIENT PREPARATION OF (E)-3-(1-CYCLOHEXENYL)-2-PROPENOIC ACID USING A PALLADIUM(II) COMPLEX-CATALYZED OLEFINATION

Abstract A convenient, three-step preparation of (E)-3-(l-cyclohexenyl)-2-propenoic acid (1) from cyciohexanone was developed, which exploited the palladium(II) complex-catalyzed olefrnation of the triflate 3 as a key step.