Chemical Innovation through Ligand Total Synthesis

Abstract

Natural products are an abundant source of synthetic challenges that foster crucial breakthroughs in organic chemistry. Despite the superior complexity of these targets, ligand total synthesis can inspire solutions to unsolved chemical problems and provide access to creative catalyst designs. This Synpacts article presents a comparative analysis of natural and ligand total synthesis to provide a context for our recent research and motivate the importance of future undertakings in this area. 1 Introduction 2 Ligands as Artificial Total Synthesis Targets 3 Natural Product Total Synthesis: The Inspiration of Relevant New Methods 4 Selected Syntheses of Important Ligands 5 Total Synthesis of the Ligand PiPy6: The Invention of a New Organometallic Photoreaction 6 Conclusion

Chiral Cyclohexyl-Fused Spirobiindanes: Practical Synthesis, Ligand Development, and Asymmetric Catalysis

“…9 In addition, such a chemical innovation can provide access to more diversified and creative catalyst design through ligand design and total synthesis. 10 In this respect, a recent report by Tan and coworkers is especially noteworthy, which disclosed the only example so far on the successful catalytic enantioselective synthesis of SPINOL and its analogues. 11 In this elegant work, chiral phosphoric acids were used as catalysts for enantioselective spirocyclization of achiral acetone derivatives, providing a variety of SPINOLs in good yields with excellent ee values.…”

“…In this context, a class of chiral ligands and organocatalysts featuring a 1,1′-spirobiindane backbone (Chart ) are extraordinarily successful, which demonstrated outstanding performance in a host of asymmetric catalytic reactions. ,− Currently, most synthetic approaches to this type of privileged ligands/catalysts relied heavily on functional group manipulation of enantiopure 1,1′-spirobiindane-7,7′-diol (SPINOL) and analogues, ,− which was generally obtained by optical resolution using substoichiometric resolving agents in the past decades. , The asymmetric catalytic construction of SPINOL and related spirobiindanes, though challenging in the broad context of chiral spirocycle synthesis, is highly attractive from the viewpoint of practical synthesis . In addition, such a chemical innovation can provide access to more diversified and creative catalyst design through ligand design and total synthesis . In this respect, a recent report by Tan and co-workers is especially noteworthy, which disclosed the only example so far on the successful catalytic enantioselective synthesis of SPINOL and its analogues .…”

Scalable Synthesis of Esp and Rhodium(II) Carboxylates from Acetylacetone and RhCl3·xH2O

“…Total synthesis has been a major resource to facilitate the supply of scarce substances and a fertile playground to create and test new chemistries . Despite the dominance of natural product and pharmaceutical targets in these studies, our group and others have used ligands to inspire synthetic innovations . The synthesis of metal catalysts offers uncharted opportunities for basic research in both organic and inorganic chemistry and can facilitate the introduction of state-of-the-art catalysts in industrial production.…”

“…Our recent studies in redox-active carbene transfer and oxidative rearrangement reactions sparked our interest to revise the current organic ,,, and inorganic synthesis methods toward Rh 2 esp 2 ( 1 ). Namely, our goal was to avoid nitrile anion alkylation in the synthesis of the ligand 2 (Scheme B) and bypass the preparation of intermediate rhodium­(II) carboxylates (i.e., 7a and b ) in the preparation of the metal complex 1 (Scheme C). ,, …”

Mechanism and regioselectivity of the anionic oxidative rearrangement of 1,3-diketones towards all-carbon quaternary carboxylates

“…These fundamental challenges add to the known background reactivity of diketones 4 with H 2 O 2 through rapid de-acylation [6][7][8][9]16,17 and Baeyer-Villiger oxidation. 19,20 In line with our interest in the synthesis of ligands and polar molecules, [21][22][23][24][25][26] we aimed to clarify the mechanism of this reaction and the fundamental role of the various additives reported. We hoped to use this knowledge to understand the complex dynamics of this system and to control the regioselectivity of the alkyl shift in unbiased acyclic substrates.…”