NHC-catalyzed [12+2] reaction of polycyclic arylaldehydes for access to indole derivatives

Abstract

An N-heterocyclic carbene (NHC) catalyzed enantio- and diastereoselective [12 + 2] cycloaddition is disclosed to rapidly construct sophisticated molecules bearing tricyclic core and morpholine moiety. The success of our reaction...

NHC-Catalyzed Reaction of Aldehydes for C(sp2)–O Bond Formation

“…Similarly, treatment of aldehyde 44 with ketoester 47 in the presence of the precursor (5aR,10bS)-A13b, Sc(OTf) 3 , CsOAc and DQ led to the formation of δ-lactone 48 in 75% yield with 94% ee [107]. As the relative examples, the [4 + 2] annulation reactions via NHC-linked ortho-quinine methide intermediate or the formal [10+2] cycloaddition reaction via NHC-linked 12π species were reported [111][112][113][114]. Additionally, the [4 + 2] annulation using azolium enolate as a C2 synthon was also developed [115,116].…”

Recent advances in metal-free catalytic enantioselective higher-order cycloadditions

“…Most recently, the enantio- and diastereoselective [12 + 2] higher-order cycloaddition between 5 H -benzo[ a ]pyrrolizine-3-carbaldehydes 73 and isatine-derivatives 61 has been developed by Chi et al via NHC-catalyzed remote C(sp 3 )–H activation (Scheme 24). 93 The reaction allows the rapid construction of a sophisticated tricyclic core bearing a morpholine moiety under mild conditions and easily accessible starting materials. Specifically, aldehydes 73 react with carbene catalyst C23 to generate the Breslow intermediate.…”

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis

“…Over the past decade, Chi, Huang, Jin and co-workers multiply reported on the NHC-catalyzed asymmetric reactions for the quick construction of novel chiral indole derivatives (Figure ). − These studies successfully achieved functionalization at the C2-, C3-, and C7-positions of the indole skeleton, with a series of novel chiral spirocyclic oxindoles or other new chiral indole-derived heterocycles afforded as the target compounds in generally moderate to excellent yields and moderate to excellent optical purities. Interestingly, these chiral indole derivatives showed promising activities against various plant bacteria, such as Ralstonia solanacearum ( Rs ), Xanthomonas oryzae pv.…”

“…In exploring the derivatization of the C3-position of indole-derived substrates, Chi, Huang, Jin, and collaborators studied a variety of novel chiral spirocyclic oxindoles or nonspirocyclic oxindoles bearing various active motifs (e.g., compounds 4 , 6 , 8 , 10 , and 12 ). − Preliminary in vitro antibacterial activities of these novel chiral products against Xoo , Xac , or Rs at different concentrations (50–100 μg/mL) were evaluated using the turbidimeter test; the experimental results showed the potential utility of several molecules in the development of innovative pesticides for crop protection. On the other hand, when derivatization reactions targeted the C7-position of indoles, , several of the corresponding chiral indole-derived compounds (e.g., 14 and 15 ) exhibited promising inhibitory activities against the plant pathogen Psa at concentrations of 100 μg/mL and 50 μg/mL, respectively.…”