Synthesis of Axially Chiral C–N Scaffolds via Asymmetric Coupling with Enantiopure Sulfinyl Iodanes

Abstract

Axially chiral C−N compounds are an emerging but scarcely investigated class of stereogenic molecules with potential applications as biologically active scaffolds and chiral ligands. The synthesis of these compounds is extremely challenging, and in particular, no metal-catalyzed asymmetric, intermolecular C−N coupling has been previously reported. Herein we disclose an intermolecular atropselective C−N coupling, occurring with excellent stereoselectivity. This Cucatalyzed transformation is based on the use of highly active coupling partners (i.e., chiral iodanes bearing a very cheap and traceless sulfoxide auxiliary). Use of such original ortho-sulfoxide iodanes enables this unprecedented coupling to occur at room temperature, guaranteeing high atropselectivity and atropselectivity of the coupling products under reaction conditions. Because of extensive possible postmodifications of the optically pure products, a panel of C−N axially chiral scaffolds can now be accessed.

Diaryliodoniums Salts as Coupling Partners for Transition-Metal Catalyzed C- and N-Arylation of Heteroarenes

“…The use of diaryliodonium salts in the N-arylation reaction of heteroarenes opens new possibilities to access the target compounds in eco-friendlier and cheaper process [105]. In addition, the N-arylated azoles have received considerable attention as key structural motifs of various bioactive molecules [106] and as ligands in synthetic chemistry [107].…”

Highly atroposelective synthesis of nonbiaryl naphthalene-1,2-diamine N-C atropisomers through direct enantioselective C-H amination

“…1a) 11–14 , due to the rotational restriction around an N-C single bond, remains largely unexplored. Until recently, the preparation of these optically active N-C nonbiaryl atropisomers still depends largely on the chiral resolution and diastereoselective synthesis using chiral pool precursors 15–17 . Only few strategies for catalytic atroposelective construction of N-C nonbiaryl atropisomers exist and mainly consist of enantioselective cyclization 18–20 , N-functionalization 21–27 , and desymmetrization 28–30 of the existing achiral N-C bond.…”

Palladium‐Catalzyed Atroposelective 16‐Membered Macrocyclization: Total Synthesis of Isoplagiochin D†

“…Six years later, the same group developed an elegant chiral sulfinyl group induced diastereoselective Heck macrocyclization of iodide 7 (Scheme 1b). [ 31‐34 ] Pleasingly, high yield (80%) and high diastereoselectivity (de 98%) have been achieved, although the modification of sulfinyl group to…”