Gold(I)‐Catalyzed and Nucleophile‐Guided Ligand‐Directed Divergent Synthesis. Issue 41 (23rd October 2018)

• Record Type: Journal Article
• Authors: Lee, Yen‐Chun; Knauer, Lena; Louven, Kathrin; Golz, Christopher; Strohmann, Carsten; Waldmann, Herbert; Kumar, Kamal
• Is Part Of: European journal of organic chemistry. Issue 41(2018)
• Page Start: 5688
• Page End: 5699
• Publication Date: 2018-10-23
• Subjects: Homogeneous catalysis -- Enynes -- Heterocycles -- Divergent synthesis -- Molecular diversity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201801080
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : 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. Abstract : 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.