Asymmetric formal C–C bond insertion into aldehydes via copper-catalyzed diyne cyclization

• Published in: Nature communications Vol. 14; no. 1; pp. 7058 - 10
• Main Authors: Li, Cui-Ting, Qi, Lin-Jun, Liu, Li-Gao, Ge, Chang, Lu, Xin, Ye, Long-Wu, Zhou, Bo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 140/131; 140/58; 639/638/403/933; 639/638/403/934; Aldehydes; Assembly; Asymmetry; Carbon; Carbonyl compounds; Carbonyls; Catalysis; Catalysts; Chemistry; Copper; Covalent bonds; Enantiomers; Homology; Humanities and Social Sciences; Insertion; Laboratories; Ligands; multidisciplinary; Phosphine; Phosphines; Reaction mechanisms; Regioselectivity; Science; Science (multidisciplinary); Stereoselectivity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-42805-2

The formal C–C bond insertion into aldehydes is an attractive methodology for the assembly of homologated carbonyl compounds. However, the homologation of aldehydes has been limited to diazo approach and the enantioselective reaction was rarely developed. Herein, we report an asymmetric formal C–C bond insertion into aldehydes through diyne cyclization strategy. In the presence of Cu(I)/SaBOX catalyst, this method leads to the efficient construction of versatile axially chiral naphthylpyrroles in moderate to excellent yields with good to excellent enantioselectivities. This protocol represents a rare example of asymmetric formal C–C bond insertion into aldehydes using non-diazo approach. The combined experimental and computational mechanistic studies reveal the reaction mechanism, origin of regioselectivity and stereoselectivity. Notably, the chiral phosphine ligand derived from synthesized axially chiral skeleton was proven to be applicable to asymmetric catalysis. The formal C–C bond insertion into aldehydes is an attractive methodology for the assembly of homologated carbonyl compounds but the homologation of aldehydes has been limited to diazo approach and the enantioselective reaction was rarely developed. Here, the authors report an asymmetric formal C–C bond insertion into aldehydes through diyne cyclization strategy