The Synthesis of Stereodefined Trisubstituted Olefins From Olefin Templates Using Pd Catalysis – Synthesis of the Antihypertensive Isbogrel

Abstract

A collection of highly functionalized, trisubstituted olefin building blocks (templates) have been developed for their Pd‐catalyzed elaboration into more complex structures, including natural products and compounds of medicinal chemistry interest. The Pd‐mediated transformations involve a combination of allylic substitution and cross‐coupling reactions. The templates have been designed such that these processes proceed not only with a high degree of regio‐ and stereoselectivity, but the transformations can all be conducted sequentially in the same flask using the same catalyst.

Comprehensive Study on Solomonamides: Total Synthesis, Stereochemical Revision, and SAR Studies toward Identification of Simplified Lead

“…After unsuccessful attempts toward macrocyclization using Friedel−Crafts reaction, we turned our attention toward cyclization at the site of aniline −NH 2 to get a model macrocyclic core of solomonamide B. Accordingly, synthesis commenced with a C−H activation reaction on N-acetyl manisidine 15 15 with known aldehyde methyl-6-oxohexanoate 16 16 using a method developed by Kwong and co-workers 17 to give the desired keto compound 17 as a single regioisomer in a 65% yield.…”

Studies toward the Synthesis of Potent Anti-inflammatory Peptides Solomonamides A and B: Synthesis of a Macrocyclic Skeleton and Key Fragment 4-Amino-6-(2′-amino-4′-hydroxyphenyl)-3-hydroxy-2-methyl-6-oxohexanoic Acid (AHMOA)

“…Accordingly, the model synthesis of a macrocycle was achieved and the results are compiled in Scheme . The model synthesis commenced with the key C–H activation step starting from known N -acyl- m -anisidine 4 and aldehyde 5 . After a few attempts, we were successful in obtaining compound 6 by employing the recently reported Li and Kwong method (Pd(TFA) 2 catalyst, TBHP in toluene) in 65% yield .…”