Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4+1] Spiroannulation

Li, Xingguang1; Guo, Jia-Xing1; Zhang, Jin2,3; Chen, Qian-Yu1; He, Yu-Jie1; Sha, Feng1; Xiang, Huijing5; Yu, Peiyuan2,3; Liu, Pei-Nian1,4

2024-06-03

10.1021/acscatal.4c01563

ACS CATALYSIS   影响因子和分区

2155-5435

Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of complex chiral three-dimensional cyclic molecules featuring quaternary carbon centers from readily available arenes. However, the asymmetric dearomatization of ubiquitous nonfunctionalized 1-naphthols to afford chiral quaternary centers remains challenging and undeveloped. This study reports the asymmetric dearomative [4 + 1] spiroannulation of nonfunctionalized 1-naphthols via copper catalysis. This reaction features a highly chemo-, regio-, and stereoselective nucleophilic addition and intramolecular annulation cascade of a reactive pi-extended copper-allenylidene, thus enabling the practical synthesis of a range of valuable spirocyclic enones bearing a chiral quaternary stereocenter with high efficiency. Furthermore, this protocol is applicable to phenols. Control experiments supported the substitution-annulation cascade mechanism by excluding a process involving a 1,3-sigmatropic shift. Preliminary biological activity studies indicated that the synthesized spirocyclic enones hold significant promise as anticancer agents by inducing tumor cell apoptosis.

dearomatization nonfunctionalized 1-naphthol spiroannulation stereoselectivity copper catalysis

SCI ; EI

英语

通讯

National Natural Science Foundation of China["22201073","21925201","22161160319","T2322018","32171391"]

Chemistry

Chemistry, Physical

WOS:001238269200001

AMER CHEMICAL SOC

Web of Science

1.East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai Key Lab Funct Mat Chem, Key Lab Adv Mat, Shanghai 200237, Peoples R China
2.Southern Univ Sci & Technol, Dept Chem, Guangdong Prov Key Lab Catalysis, Shenzhen 518055, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Guangdong Prov Key Lab Catalysis, Shenzhen 518055, Peoples R China
4.China Pharmaceut Univ, Sch Pharm, State Key Lab Nat Med, Nanjing 210009, Peoples R China
5.Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China

Li, Xingguang,Guo, Jia-Xing,Zhang, Jin,et al. Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4+1] Spiroannulation[J]. ACS CATALYSIS,2024,14(12).

Li, Xingguang.,Guo, Jia-Xing.,Zhang, Jin.,Chen, Qian-Yu.,He, Yu-Jie.,...&Liu, Pei-Nian.(2024).Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4+1] Spiroannulation.ACS CATALYSIS,14(12).

Li, Xingguang,et al."Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4+1] Spiroannulation".ACS CATALYSIS 14.12(2024).