Search

The first synthetic access to stable and acyclic 1,3‐butadienes with two electron‐withdrawing carbonyl groups and their potential to deliver new molecular scaffolds through intriguing endo‐selective Diels–Alder cycloadditions are presented. The bicyclic scaffolds produced through the cycloaddition chemistry of electron‐deficient dienes afforded potent Hedgehog signaling pathway inhibitors. Uniquely deficient! A facile synthetic access to stable, electron‐deficient and acyclic 1,3‐butadienes bearing two orthogonal electron‐withdrawing groups is presented. This method opens the door to many molecular frameworks, including new Hedgehog pathway inhibitors. [ABSTRACT FROM AUTHOR]

Transition metal catalysts can mediate a plethora of skeleton rearrangements of a range of substrates to construct complex small molecules. Yet, their potential to transform common substrates into distinct molecular scaffolds has not been fully explored to deliver biologically relevant small molecules. Gold(I)‐catalyzed transformations of enynes are amongst the most intriguing rearrangements and provide opportunities to access a range of diverse scaffolds efficiently. In ligand‐directed divergent synthesis (LDS), variation of ligands in metal complexes determines the fate of substrates during their transformation into distinct scaffolds. For instance, variation of ligands for the gold(I) catalysts helps to transform oxindole derived 1,6‐enynes into several distinct molecular frameworks. In this report, we present how ligand variation in gold(I) catalysts, nucleophile‐additives and alkyl and alkynyl substitutions on the 1,6‐enynes as well as replacement of the oxindole ring with a different privileged ring‐system (PRS) influence the LDS approach to access a wider chemical space. Based on the experimental results, we propose several mechanistic pathways in gold(I)‐catalyzed cycloisomerizations and cascade reactions of 1,6‐enyne substrates leading to structurally distinct chemotypes. A ligand‐directed divergent scaffold synthesis was explored by varying the ligands for the gold(I) catalysts and the nucleophiles in the cycloisomerization reactions of oxindole based 1,6‐enynes. The strategy afforded several distinct and structurally complex molecular scaffolds. [ABSTRACT FROM AUTHOR]

The reaction of benzyl lithiums is an important aspect in organic and organometallic synthesis. Reported herein are detailed insights into the reactivity of benzyl lithiums as regulated by intermediate structures. By discussing the carbometalation of allylamines and the reaction of the formed benzyl-lithium compounds with electrophiles, the influence of the metal as well as the solvent on the electronic structure of the intermediate is described. This molecular structure strongly influences the reactivity of these intermediates. By choosing the appropriate reaction conditions, the regioselectivity of reactions with electrophiles can be regulated. With trimethylchlorosilane in n-pentane a selective reaction at the para-position takes place. In contrast, selective reaction at the benzylic position, with trimethylchlorostannane in tetrahydrofuran (THF) as a solvent, is accomplished. [ABSTRACT FROM AUTHOR]