Xiaoyong Fu

A copper-free palladium catalyzed cross coupling reaction of vinyl tosylates with terminal acetylenes

A copper-free palladium-catalyzed cross coupling of vinyl tosylate (2) and terminal acetylenes was investigated, affording a convenient and efficient method for construction of an sp–sp2 carboncarbon bond. The tosylate (2) derived from 1,3-cyclohexanedione was reacted with terminal acetylene under the copper-free conditions at ambient temperature, in the presence of palladium acetate and triphenylphosphine, to provide the conjugated en-yn-one products in excellent overall yields while leaving other functional groups intact. This reaction protocol was extended to coumarin tosylate (12).

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.

Two new C-nor/D-homo corticosteroids formed by dehydration rearrangement of a 12β-hydroxy corticoid

Two new C-nor/D-homo corticosteroids were isolated from the filtrate of the triene carbonate intermediate during the production of betamethasone. Their structures were elucidated based on NMR spectroscopic studies and mass spectral analyses. The mechanism of formation of each of these two steroids was postulated as a Wagner-Meerwein rearrangement of the corresponding 12beta-hydroxy steroid. The new 12beta-hydroxy corticosteroid was also isolated from the fermentation process of betamethasone synthesis. Its structure was identified via NMR and mass spectroscopic studies. Treatment of the new 12beta-hydroxy corticoid with PCl(5) at low temperature provided two C-nor/D-homo compounds in a ratio of 1:1. Conversion of 12beta-hydroxy corticoid into a corresponding 12beta-mesylate followed by heating in HOAc to 110 degrees C in the presence of NaOAc produced a mixture of the rearranged products in a 1:4 ratio.

A regioselective PCl5 mediated dehydration for preparing Δ9,11 corticosteroids

Abstract A regioselective PCl 5 -induced dehydration of 11α-hydroxy corticosteroids was invented to provide the corresponding Δ 9,11 double bond trienes in excellent yield (>90%) with 99:1 regioisomeric ratio to the Δ 11,12 isomers. A syn -elimination mechanism was proposed for this reaction.