Synthesis of Large Macrocycles with Chiral Sulfur Centers via Enantiospecific SuFEx and SuPhenEx Click Reactions

[Image: see text] Here we report the first asymmetric synthesis of large chiral macrocycles with chiral sulfur atoms. Building on stereospecific SuFEx and SuPhenEx click chemistries, this approach utilizes disulfonimidoyl fluorides and disulfonimidoyl p-nitrophenolates—which are efficient building blocks with two chiral sulfur centers, and diphenols to efficiently form novel S–O bonds. Characteristic results include the enantiospecific one-step synthesis of rings consisting of 21–58 members and characterization of both enantiomers (R,R and S,S) by e.g. X-ray crystallography.