Application of the Solid-Supported Glaser–Hay Reaction to Natural Product Synthesis

Abstract

The Glaser–Hay coupling of terminal alkynes is a useful synthetic reaction for the preparation of polyynes; however, chemoselectivity issues have precluded its widespread utilization. Conducting the reaction on a solid-support provides a mechanism to alleviate the chemoselectivity issues and provide products in high purities and yields. Moreover, the polyyne core is a key component to several natural products. Herein, we describe the application of a solid-supported Glaser–Hay reaction in the preparation of several natural products. These compounds were then screened for antibacterial activity, illustrating the utility of the methodology.

Iron-Catalyzed Cadiot–Chodkiewicz Coupling with High Selectivity in Water under Air

“…To further extend the applicability of this system, we next focused on the synthesis of 1,3,5-hexatriynes, which are conventionally prepared by the Fritsch–Buttenberg–Wiechell rearrangement, Pd-catalyzed alkynyl–alkenyl coupling, Cu-catalyzed Glaser–Hay coupling, and Cu- or Pd/CuI-catalyzed Cadiot–Chodkiewicz coupling. , In order to avoid the polymerization of terminal 1,3-butadiyne at a high concentration, trimethylsilyl-protected 1,3-butadiynes, 5 , were employed to couple with 1 via a one-pot reaction. Unfortunately, desilylation did not take place in neat water in the presence of KOH, and hence, MeOH was utilized as a cosolvent to achieve the production of terminal 1,3-butadiynes.…”

Cu/Cu2O Nanoparticles Supported on a Phenol–Pyridyl COF as a Heterogeneous Catalyst for the Synthesis of Unsymmetrical Diynes via Glaser–Hay Coupling

“…However, can it display the same level of activity and selectivity toward heterocoupled products? This is something that has been evading in the other heterogeneous Cu catalysts. − The catalytic reaction was carried out in a CHCl 3 –dioxane solvent system with an optimal catalyst loading of 0.0992 mol %. The reaction was performed in the open air, and it completed within 4 h. The catalyst was easily removed from the reaction mixture by centrifugation, and the product mixture was characterized using a range of techniques.…”

“…Unsymmetrical 1,3-diynes are an important class of intermediates in organic synthesis and key motifs in many natural products and functional materials. − Partial reduction and metal-assisted electronic manipulations at these diyne cores unlock diverse chemistry. − Thus, developing methodologies for the synthesis of novel diynes, in particular, unsymmetrical diynes, is rewarding. Although homogeneous catalysts − have been systematically developed for the synthesis of homocoupled 1,3-diynes through the Glaser–Hay coupling, attempts to make unsymmetrical 1,3-diynes by coupling two different aryl or alkyl substrates have been marred by poor selectivity. − Very few heterogeneous Cu-based catalysts have been developed, but they give predominantly homocoupling products. − Recently, Yin and co-workers reported a Cu-based homogeneous catalyst, wherein [CuCl 4 ] 2– units generated by adding metallic copper to N 1, N 1, N 2, N 2-tetramethylethylenediamine (TMEDA) in chloroform catalyze the heterocoupling of alkynes quite effectively …”

Rise of Conjugated Poly-ynes and Poly(Metalla-ynes): From Design Through Synthesis to Structure–Property Relationships and Applications

“…Using a scaffold-hopping approach, Kurasaki and co-workers 888 showed excellent activity in the nanomolar range against different strains of bacteria. Young and co-workers 889 reported the antibacterial efficiency of several semisynthetic oligo-ynes 475−476. The acetylenic compounds which were synthesized via solid-supported Glaser Hay coupling showed moderate antibacterial potential.…”