Enantioselective Tandem Cyclization of Alkyne‐Tethered Indoles Using Cooperative Silver(I)/Chiral Phosphoric Acid Catalysis

Zhu, Yugen; He, Wei; Wang, Wei; Pitsch, Chloe E.; Wang, Xiaotai; Wang, Xiang

doi:10.1002/ange.201706694

Cited by 14 publications

(1 citation statement)

References 71 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Later on, Glorius group described an elegant and highly enantioselective formal [3+2] cyclization reaction of azaaurones with α,β‐unsaturated aldehydes to access C2‐spiro indoline by N ‐heterocyclic carbene (NHC) catalysis . Recently, Wang group developed the synthesis of tetracyclic indolines through a Ag(I)‐chiral phosphoric acid cooperatively catalyzed tandem cyclization of alkyne‐tethered indoles . In spite of their significant achievements, it is still very much in demand to develop novel and efficient protocols to construct and modify C2‐spiro indolines so that the structural diversity of these biologically important heterocyclic frameworks could be further expanded.…”

Section: Figurementioning

confidence: 99%

Organocatalytic Asymmetric Cyclization Reaction of 2‐Alkynyl‐3,3‐Difluoro‐3H‐Indoles and 2‐Mercaptoimidazoles: Access to gem‐Difluorinated C2‐Spiro Indolines

et al. 2019

View full text Add to dashboard Cite

We reported a cupreidine catalyzed enantioselective cascade cyclization reaction of 2alkynyl-3,3-difluoro-3H-indole and 2-mercaptoimidazole under simple and mild conditions. The corresponding chiral gem-difluorinated C2-spiro indolines were obtained in moderate to good yields and enantioselectivities, which could be interesting compounds from synthetic and medicinal chemistry points of view. This work represents the first catalytic enantioselective example of utilizing 2alkynyl-3,3-difluoro-3H-indoles as the bis-electrophiles in a cyclization reaction.

show abstract

Section: Figurementioning

confidence: 99%

Organocatalytic Asymmetric Cyclization Reaction of 2‐Alkynyl‐3,3‐Difluoro‐3H‐Indoles and 2‐Mercaptoimidazoles: Access to gem‐Difluorinated C2‐Spiro Indolines

et al. 2019

View full text Add to dashboard Cite

show abstract

Organocatalytic Synthesis of gem‐Difluorinated C2‐Spiro Indolines and Pyrimido[1,2‐a]benzimidazoles from 2‐Alkynyl‐3,3‐Difluoro‐3H‐Indoles

et al. 2018

View full text Add to dashboard Cite

In this communication, we report a substrate-controlled product diversity in the 1,5,7triazabicyclo[4.4.0]dec-5-ene (TBD)-catalyzed cascade cyclization of 2-alkynyl-3,3-difluoro-3H-indoles with N,N-or N,S-bis-nucleophiles. The products represent two important heterocyclic compounds, C2-spiro indoline, and pyrimido[1,2-a] benzimidazole, featuring a versatile gem-difluoromethylene group on the framework. In these cascade processes, two new CÀN bonds, or one CÀS and one CÀN bond, are consecutively formed in a single step. The present protocol is characterized with high regioselectivity, high yield, broad substrate scope, good functional group tolerance, facile scalability and mild reaction conditions.

show abstract

Catalytic Asymmetric Dearomatization of Indolyl Dihydropyridines through an Enamine Isomerization/Spirocyclization/Transfer Hydrogenation Sequence

et al. 2018

View full text Add to dashboard Cite

Ah ighly efficient synthesis of enantioenriched spiroindolines by catalytic asymmetric dearomatization of indolyl dihydropyridines through ac hiral phosphoric acid catalyzede namine isomerization/spirocyclization/transfer hydrogenation sequence has been developed. This reaction proceeds under mild reaction conditions,a ffording novel spiroindolines in good yields (up to 88 %) with excellent enantioselectivity (up to 97 %e e). DFT calculations provide insights into the reaction mechanism as well as the origin of stereochemistry.Synthetic studies of polycyclici ndole derivatives have attracted plenty of research interests due to the widespread occurrence of such structural cores in natural products as well as their biological activities. [1] Pictet-Spengler reactions are widely recognized as one of the most efficient and straightforward methods to afford tetrahydro-b-carbolines. [2] Tr aditionally,t ryptamine derivatives and carbonyl compounds are employed as the substrates of Pictet-Spengler reactions.A s part of our ongoing research on catalytic asymmetric dearomatization (CADA) reactions, [3] we recently developed an efficient asymmetric synthesis of tetrahydro-b-carbolines 2 through chiral phosphoric acid (CPA)-catalyzed sequential enamine isomerization/Pictet-Spengler reaction of indolyl dihydropyridines 1 (Scheme 1a). [4] Spiroindolenine has been generally regarded as ak ey intermediate in Pictet-Spengler reactions.T oc apture and further manipulate the spiroindolenine species would allow unprecedented access to novel polycyclic indole derivatives. [5] In this regard, we envisioned that the analogous reaction of indolyl dihydropyridine 3, which bears aone-methylene prolonged tether, would afford spiroindolenine 4,f rom which an in situ transfer hydrogenation with Hantzsch ester might lead to tetrahydrospiro[indoline-3.1'-quinolizine] 5 (Scheme 1b). Herein, we report the results of the study on this cascade reaction catalyzed by achiral phosphoric acid. [6] Our studies commenced with optimization of the reaction conditions with 3a as the model substrate (Table 1). It was Scheme 1. Reaction design. Table 1: Optimization of the reaction conditions. [a] Entry CHSolvent T [8 8C] t [h] Yield [%] ee [%] [b] 1 C1 H1 Cl(CH 2 ) c] C1 H1 EtOAc 40 36 82 93 [a] Unless otherwise noted, the reaction was performed with 3a (0.1 mmol), C (10 mol %), H (0.2 mmol) in 2.0 mL solvent. [b] Determined by HPLC analysis on achiral stationary phase. [c] 50 mg 3 MS were added and 6mLofEtOAc were used.found that in the presence of 10 mol %o fc hiral phosphoric acid C1 and 2.0 equiv of Hantzsch ester H1,the title reaction proceeded smoothly,d elivering the desired product 5a in 83 %y ield with 81 % ee as asingle diastereoisomer (Table 1, entry 1). Systematic evaluation of aseries of chiral phosphoric acids (C2-C7)r evealed that all of the catalysts tested can promote the reaction, albeit with varied yields and enantioselectivity (entries 2-7). With C1 as the optimal catalyst, the effects of different hydride donors were then examined. The...

show abstract

Enantioselective Tandem Cyclization of Alkyne‐Tethered Indoles Using Cooperative Silver(I)/Chiral Phosphoric Acid Catalysis

Cited by 14 publications

References 71 publications

Organocatalytic Asymmetric Cyclization Reaction of 2‐Alkynyl‐3,3‐Difluoro‐3H‐Indoles and 2‐Mercaptoimidazoles: Access to gem‐Difluorinated C2‐Spiro Indolines

Organocatalytic Asymmetric Cyclization Reaction of 2‐Alkynyl‐3,3‐Difluoro‐3H‐Indoles and 2‐Mercaptoimidazoles: Access to gem‐Difluorinated C2‐Spiro Indolines

Organocatalytic Synthesis of gem‐Difluorinated C2‐Spiro Indolines and Pyrimido[1,2‐a]benzimidazoles from 2‐Alkynyl‐3,3‐Difluoro‐3H‐Indoles

Catalytic Asymmetric Dearomatization of Indolyl Dihydropyridines through an Enamine Isomerization/Spirocyclization/Transfer Hydrogenation Sequence

Contact Info

Product

Resources

About