Enantioselective Dearomatization of Indoles by an Azoalkene‐Enabled (3+2) Reaction: Access to Pyrroloindolines

Mei, Guang‐Jian; Tang, Xiwen; Tasdan, Yildiz; Lü, Yixin

doi:10.1002/ange.201911686

Cited by 15 publications

(3 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, given the results with the use of both 2,3- and 3-unsubstituted indoles (associated with the [4 + 2] pyridazine-ring-opening reaction) and to further showcase the flexibility of this catalytic annulation strategy, we next moved our attention to exploring the reactivity of C3-blocked indoles ( e.g ., 3-substituted and 2,3-disubstituted indoles) with DDs. To our surprise, the reaction of 3-methyl indole ( 1p ) with linear DD 2n led to a mixture of two cycloadducts, the expected tetrahydro-1 H -pyridazino[3,4- b ]indole compound 3ab and the tetrahydropyrrolo[2,3- b ]indole compound 5a ( 14 ) in a ratio of approximately 1:1, which could possibly be the result of the above-mentioned two competitive reaction pathways 15 ( Scheme 2 ). Interestingly, when 1,3-dimethyl indole ( 1q ) was used in combination with DD 2j , the exclusive formation of product 5b (46% yield) was detected.…”

Section: Resultsmentioning

confidence: 96%

Synthesis of Polycyclic Fused Indoline Scaffolds through a Substrate-Guided Reactivity Switch

Ciccolini

Mari

Gatti³

et al. 2020

J. Org. Chem.

View full text Add to dashboard Cite

Zn(II)-catalyzed divergent synthesis of functionalized polycyclic indolines through formal [3 + 2] and [4 + 2] cycloadditions of indoles with 1,2-diaza-1,3-dienes (DDs) is reported. The nature and type of substituents of substrates are found to act as a chemical switch to trigger two distinct reaction pathways and to obtain two different types of products upon the influence of the same catalyst. The mechanism of both [4 + 2] and [3 + 2] cycloadditions was investigated and fully rationalized by density functional theory (DFT) calculations.

show abstract

Section: Resultsmentioning

confidence: 96%

Synthesis of Polycyclic Fused Indoline Scaffolds through a Substrate-Guided Reactivity Switch

Ciccolini

Mari

Gatti³

et al. 2020

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…A large number of new reviews [ 26 , 27 , 56 , 57 ] and original publications [ 31 , 58 , 59 , 60 , 61 , 62 ], which appeared in the last four years, demonstrates the growing interest in the chemistry of azoalkenes and their applications in hetero -Diels-Alder reactions. The presented study showed important mechanistic aspects and demonstrated that scarcely known 3,6-dihydro-2 H -1,3,4-thiadiazines can efficiently be prepared by regioselective hetero -Diels-Alder reactions of thioketones with in situ-generated azoalkenes, bearing an electron-withdrawing substituent at the terminal N-atom.…”

Section: Discussionmentioning

confidence: 99%

Hetero-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies

et al. 2021

View full text Add to dashboard Cite

The hetero-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2H-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27–2.58 Å) and longer N..C-distances (3.02–3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4-tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C‒S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies.

show abstract

“…In 2019, Lu et al established the first metal-free enantioselective dearomatization addition of indoles 210 to access chiral pyrroloindoline cores 220 (Scheme 61). [70] Such a convergent approach takes utmost care to highly reactive conjugated azoalkenes 219 as an exceptional reaction partner. The reaction was performed under mild reaction conditions, and over a wide range of pyrroloindolines 220 were obtained in good to excellent yields and with excellent.…”

Section: Through Chiral Phosphine-/phosphoric Acid-catalysismentioning

confidence: 99%

Asymmetric Catalytic Approaches Employing α,β‐Unsaturated Imines

et al. 2023

View full text Add to dashboard Cite

Nitrogen-containing heterocyclic compounds have consistently been a noticeable center of attention due to their significant utilization in the domain of synthetic organic chemistry, agrochemicals, and pharmaceuticals. α,β-Unsaturated imines or conjugated imines provide a lot of significant cyclic as well as acyclic products through reacting with a versatile family of compounds. This review summarizes the recent advances in enantioselective reactions of α,β-unsaturated imines by using synthetic methodologies for synthesizing various nitrogencontaining heterocycles that contain four to six-membered rings. The synthesis of rarely found seven-, eight-and ninemembered nitrogen-containing heterocycles have also been reported.

show abstract

Enantioselective Dearomatization of Indoles by an Azoalkene‐Enabled (3+2) Reaction: Access to Pyrroloindolines

Cited by 15 publications

References 115 publications

Synthesis of Polycyclic Fused Indoline Scaffolds through a Substrate-Guided Reactivity Switch

Synthesis of Polycyclic Fused Indoline Scaffolds through a Substrate-Guided Reactivity Switch

Hetero-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies

Asymmetric Catalytic Approaches Employing α,β‐Unsaturated Imines

Contact Info

Product

Resources

About