Synthesis of Single Isomer Trisubstituted Olefins from beta-chloro-alpha-iodo-alpha, beta-Unsaturated Esters and Alkynyl Esters

Abstract

A convenient method to synthesize regiospecific and stereoselective trisubstituted olefins bearing three substitutents with various functionalities is disclosed. A unique olefin template such as (E)-beta-chloro-alpha-iodo-alpha,beta-unsaturated esters cross-couple with 9-alkyl-9-BBN to produce single isomer trisubstituted olefins using palladium-catalyzed Suzuki-Miyaura cross-coupling reaction. This methodology can be further expanded to introduce various alkyl groups at the beta-position. The mechanism is somewhat unusual as it involves two catalytic cycles with an allenoate intermediate to explain the observed stereochemistry and protonolysis of that intermediate produces the key product, (E)-beta-chloro-alpha,beta-unsaturated ester. The protonolysis is mediated by the presence of H2O in the inorganic base, K3PO4·H2O.* Similarly, another method has been developed to synthesize trisubstituted olefins using the alkynyl ester and 9-alkyl-9-BBN. This process also has a broad scope to introduce various alkyl groups at the beta-position. The mechanism currently proposed involves an oxidation of palladium to form H-[Pd]-OH species. This was confirmed based on the importance of water in the catalytic system and the isotopic experiments also confirmed the olefinic hydrogen at the alpha-position arises from the water itself. Following the formation of H-[Pd]-OH, syn carbopalladation to the alkynyl ester creates the hydroxyl palladium vinyl intermediate. However, this mechanism does not explain the observed stereochemistry. A more detailed study is required regarding this mechanism.* *Please refer to dissertation for diagrams.