Rh(I)-Catalyzed Chemo- and Stereoselective Domino Cycloaddition of Optically Active Propargyl 2,4-Hexadienyl Ethers

Abstract

1,1'-Bi-2-naphthol in combination with ZnEt2, Ti(O(i)Pr)4, and dicyclohexylamine have been employed to catalyze asymmetric alkyne addition to an ynal to synthesize optically active propargylic alcohols containing two alkyne functions with excellent yields and enantioselectivities. These chiral alcohols are readily converted to the corresponding optically active propargyl 2,4-hexadienyl ethers. These diene-diyne substrates are found to undergo a highly chemoselective and stereoselective domino Pauson-Khand and Diels-Alder cycloaddition catalyzed by [RhCl(CO)2]2 under CO to generate a class of tetracyclic compounds with high enantiomeric purity. This is a very efficient method for the asymmetric synthesis of polycyclic compounds.

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation

“…Under rhodium(I) catalyst and CO atmosphere, a cascade cycloaddition comprising Pauson-Khand and Diels-Alder reaction proceeds smoothly in a highly chemoselective and stereoselective fashion. The following year, they (Ying et al, 2015) extended this strategy for various branched precursor with two alkynes and a diene group to access several natural product-like tetracyclic carbocycles ( Figure 3B). The group of Gong and Yang reported construction of 5/5/6-strained polycyclic system via cobalt/thiourea-catalyzed Pauson-Khand reaction and a cascade 6π electrocyclization ( Figure 3C).…”