Chiral Primary Amine Catalysis for Asymmetric Mannich Reactions of Aldehydes with Ketimines: Stereoselectivity and Reactivity

Dai, Jing; Xiong, Dan; Yuan, Tengrui; Liu, Juan; Chen, Tao; Shao, Zhihui

doi:10.1002/ange.201706304

Cited by 20 publications

(7 citation statements)

References 107 publications

(13 reference statements)

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“…Firstly, as shown in Scheme 3B, the allylation product 3a underwent complete oxidation and reduction to give the compound 7 . Compound 7 can be oxidized to an aldehyde intermediate and provided key compound 8 by reductive amination, which can be converted to (−)-psychotriasine (Dai et al., 2017). Compound 3a underwent hydroboration-oxidation followed by an intramolecular Mitsunobu reaction to afford spirocyclic amine 10 (98.7:1.3 er ).…”

Section: Resultsmentioning

confidence: 99%

Bi(III)-Catalyzed Enantioselective Allylation Reactions of Ketimines

et al. 2019

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Summary Chiral homoallylic amines not only are found in pharmaceutically relevant compounds but also serve as versatile building blocks for chemical synthesis. However, catalytic allylation of ketimines with allylboronates, an attractive approach to synthesize chiral homoallylic amine scaffolds remain scarce. Herein, we develop a highly enantioselective allylation of isatin-derived ketimines with boron allylation reagents catalyzed by a Bi(OAc) 3 -chiral phosphoric acid catalyst system. The reactions are remarkably efficient and mild, most of which were completed in less than an hour at room temperature with only 1/2 mol% (Bi(OAc) 3 /CPA) catalyst loading. A wide range of chiral 3-allyl 3-aminooxindoles were obtained in excellent yields and enantioselectivities. The synthetic utility was demonstrated by efficient formal synthesis of (+)-AG-041R and (−)-psychotriasine. Preliminary mechanism was studied by control experiments and theoretical calculations.

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Section: Resultsmentioning

confidence: 99%

Bi(III)-Catalyzed Enantioselective Allylation Reactions of Ketimines

et al. 2019

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“…N ‐Arylation of 302 followed by a palladium‐catalyzed cyclization afforded (−)‐psychotriasine ( 306 , Scheme 33). [60] …”

Section: Applications In Natural Product Synthesismentioning

confidence: 99%

“…[59] In 2017, Shao and co-workers realized the enantioselective total synthesis of (-)-psychotriasine (306, Scheme 33). [60] Using an asymmetric Mannich reaction between the N-Boc-isatin ketimine 297 and acetaldehyde (12) catalyzed by a chiral primary amine catalyst 298, they obtained the key isatin intermediate 299. Further transformations of 299 afforded the tricyclic intermediate 300 after several steps of synthetic maneuvers.…”

Section: Primary Amine Catalystsmentioning

confidence: 99%

Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

2021

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Natural products are the great sources of drugs and leading compounds in drug discovery, as it has been estimated that most of the current medicines are derived from natural products. Total synthesis of natural products, especially those of biological activities, has been an important part of organic chemistry, which, besides its potential practical utilities, also provides new inspirations and novel synthetic methodologies. Over the past two decades, organocatalysis has been shown to be very effective in controlling the stereochemistry of the reaction products and has found many applications in the asymmetric synthesis of natural products and related compounds. In this review we will attempt to summarize some applications of asymmetric organocatalysis in the total synthesis of natural products and related compounds in the past seven years.

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“…Bhadury and Song reviewed the mechanism and the stereochemistry of organocatalytic asymmetric Mannich reactions [60], Cai and Xie provide an overview of asymmetric Mannich reactions with different organocatalysts, such as: chiral Brønsted acids, chiral amines, chiral bifunctional thiourea, and others [61]. In recent years, the stereoselective asymmetric Mannich reactions of aldehydes catalyzed by chiral primary amine were reported by Dai et al [62], enantioselective Mannich syntheses promoted by chiral phosphinoyl-aziridines [63], asymmetric Mannich reactions to generate chiral β-amino esters [64], and copper-catalyzed enantioselective Mannich reactions of N-acylpyrazoles and isatin [65].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, density functional theory study and in vitro antimicrobial evaluation of new benzimidazole Mannich bases

et al. 2020

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The tri-component synthesis of novel chiral benzimidazole Mannich bases, by reaction between benzimidazole, aqueous 30% formaldehyde and an amine, the biological evaluation and DFT studies of the new compounds are reported here. The 1 H-NMR, 13 C-NMR, FTIR spectra and elemental analysis confirm the structures of the new compounds. All synthesized compounds were screened by qualitative and quantitative methods for their in vitro antibacterial activity against 4 bacterial strains. DFT studies were accomplished using GAMESS 2012 software and HOMO-LUMO analysis allowed the calculation of electronic and structural parameters of the chiral Mannich bases. The geometry of 1-methylpiperazine, the cumulated Mullikan atomic charges of the two heteroatoms and of the methyl, and the value of the global electrophilicity index (ω = 0.0527) of the M-1 molecule is correlated with its good antimicrobial activity. It was found that the presence of saturated heterocycles from the amine molecule, 1-methyl piperazine and morpholine, respectively, contributes to an increased biological activity, compared to aromatic amino analogs, diphenylamino-, 4-nitroamino-and 4-aminobenzoic acid. The planarity of the molecules, specific bond lengths and localization of HOMO-LUMO orbitals is responsible for the best biological activities of the compounds.

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Chiral Primary Amine Catalysis for Asymmetric Mannich Reactions of Aldehydes with Ketimines: Stereoselectivity and Reactivity

Cited by 20 publications

References 107 publications

Bi(III)-Catalyzed Enantioselective Allylation Reactions of Ketimines

Bi(III)-Catalyzed Enantioselective Allylation Reactions of Ketimines

Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

Synthesis, density functional theory study and in vitro antimicrobial evaluation of new benzimidazole Mannich bases

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