Although chiral sulfoxides are important motifs in medicinal chemistry and asymmetric synthesis, design and applications of sulfoxide ligands are still limited, in particular in the context of asymmetric C−H activation. We disclose herein the conception and synthesis of enantiopure N/S ligands: N-protected aminosulfoxides. The potential of these auxiliaries in asymmetric C(sp 3 )−H activation is demonstrated as high enantioselectivity is reached during a Pdcatalyzed direct arylation of cyclopropane carboxylic acid derivatives. Besides, the capacity of these ligands goes far beyond as yet unknown direct alkynylation could also be performed with an enantiomeric ratio up to 92:8. The preliminary mechanistic studies shed light on their original mode of action including: 1) key noncovalent interactions between the chiral complex and the substrate allowing stabilization of agostic M−H−C interaction and 2) π-stacking ligand-substrate bonding. DFT investigations suggest that, thanks to this unusual ligand/substrate activation, commonly recognized as difficult, the cleavage of the C−H bond is virtually barrier-less.
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.
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