Catalytic enantio- and diastereoselective Mannich reaction of α-substituted isocyanoacetates and ketimines

Campa, Raquel de la; Yamagata, Adam D. Gammack; Ortín, Irene; Franchino, Allegra; Thompson, Amber L.; Odell, Barbara; Dixon, Darren J.

doi:10.1039/c6cc04132a

Cited by 59 publications

(24 citation statements)

References 43 publications

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“…In the same year, Dixon and co-workers described another enantioselective Mannich type reaction of diphenylphosphinoyl protected ketimines (172) and αsubstituted isocyanoacetates (173) to synthesize vicinal tetra-substituted 2-imidazolines (Scheme 50). [60] Similar to their previous report, [49] the reaction utilized silver(I) salt and cinchona-derived amide catalyst (176) to synthesize the protected imidazoline (174). Then, 1 M HCl in DCM was used to obtain the deprotected imidazoline (175).…”

Section: Methods B: Synthesis Of Imidazolines From Isocyanidesmentioning

confidence: 70%

Recent Advances in the Synthesis of Imidazolines (2009–2020)

Mehedi

Tepe

2020

Adv Synth Catal

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Imidazoline is an important class of compounds found in numerous natural and pharmaceutical products. The compounds are also used as an intermediate in the synthesis of organic molecules. Moreover, chiral imidazolines are widely utilized as organocatalysts to synthesize various natural and synthetic organic compounds. In the past decade, there was an increase in interest in developing new methods to synthesize these imidazoline analogs. Both modification of the previously established methods and the development of new methods are carried out significantly. This review article highlights the progress of the synthesis of imidazoline scaffolds in the last few years (2009-present). The review also described the proposed mechanism illustrated in many of the reports.

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Section: Methods B: Synthesis Of Imidazolines From Isocyanidesmentioning

confidence: 70%

Recent Advances in the Synthesis of Imidazolines (2009–2020)

Mehedi

Tepe

2020

Adv Synth Catal

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“…Ligand 1 d devoid of the phosphine moiety delivered the product in only 8 % yield and in racemic form (entry 4), and the addition of 10 mol % exogenous triphenylphosphine did not improve its performance significantly (entry 5), highlighting the importance of a bidentate N,P‐ligand for reactivity and stereocontrol. Amino phosphine 1 e with a methylated amide linker promoted the reaction with diminished reactivity, and lower diastereo‐ and enantioselectivity (61 % conversion, 83:17 d.r., 88 % ee , entry 6), suggesting that the NH of the linker plays a role in the reaction . Ligand 1 f possessing an ester linker afforded product ent ‐5 a in 50 % yield with 90 % ee (entry 7): replacement of the NH group by an O atom decreased the reactivity and imparted a switch in the enantiofacial selectivity for both reaction partners, even if ligands 1 b and 1 f on their own display nearly superimposable crystal structures…”

Section: Methodsmentioning

confidence: 99%

“…Based on single‐crystal X‐ray diffraction and NMR studies providing evidence of complex formation between AgOAc and N,P‐ligand 1 b , we performed a computational analysis of competing transition structures (TSs) (Figure ). Since N ‐DPP ketimines exist as a mixture of E ‐ and Z ‐configurated stereoisomers rapidly interconverting at room temperature, we examined both configurations computationally.…”

Section: Methodsmentioning

confidence: 99%

Catalytic Enantio‐ and Diastereoselective Mannich Addition of TosMIC to Ketimines

Franchino

Chapman

Funes‐Ardoiz

et al. 2018

Chemistry A European J

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Chiral amines bearing a stereocenter in the α position are ubiquitous compounds with many applications in the pharmaceutical and agrochemical sectors, as well as in catalysis. Catalytic asymmetric Mannich additions represent a valuable method to access such compounds in enantioenriched form. This work reports the first enantio‐ and diastereoselective addition of commercially available p‐toluenesulfonylmethyl isocyanide (TosMIC) to ketimines, affording 2‐imidazolines bearing two contiguous stereocenters, one of which is fully‐substituted, with high yields and excellent stereocontrol. The reaction, catalyzed by silver oxide and a dihydroquinine‐derived N,P‐ligand, is broad in scope, operationally simple, and scalable. Derivatization of the products provides enantioenriched vicinal diamines, precursors to NHC ligands and sp3‐rich heterocyclic scaffolds. Computations are used to understand catalysis and rationalize stereoselectivity.

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“…Looking to expand the diversity of product types accessible we considered isocyanides 51 – 53 as potential nucleophiles. Based on the known interaction between hemiaminals 10 and isocyanides and our own prior experience with both partners 43 – 45 , 54 – 56 , we hypothesized that isocyanides might, in the presence of an acid promoter, intercept the in situ formed iminium species, thus generating versatile nitrilium intermediates applicable for various Ugi-type reactions (Fig. 1d ).…”

Section: Introductionmentioning

confidence: 99%

Iridium-catalyzed reductive Ugi-type reactions of tertiary amides

Xie

Dixon

2018

Nat Commun

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Amides are ubiquitous in the fine chemical, agrochemical and pharmaceutical industries, but are rarely exploited as substrates for homologous amine synthesis. By virtue of their high chemical stability, they are essentially inert to all but the harshest of chemical reagents and to the majority of chemical transformations routinely used in organic synthesis. Accordingly, the development of chemoselective carbon−carbon bond-forming methodologies arising from the functionalization of the amide functionality should find widespread use across academia and industry. We herein present our findings on a series of Ugi-type reactions of tertiary amides enabled by an initial chemoselective iridium-catalyzed partial reduction, followed by reaction with isocyanide and (thio)acetic acid or trimethylsilyl azide, thus providing a multicomponent synthesis of α-amino (thio)amide or α-amino tetrazole derivatives. The reductive Ugi-type reactions are amenable to a broad range of amides and isocyanides, and are applicable to late-stage functionalization of various bioactive molecules and pharmaceutical compounds.

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Catalytic enantio- and diastereoselective Mannich reaction of α-substituted isocyanoacetates and ketimines

Cited by 59 publications

References 43 publications

Recent Advances in the Synthesis of Imidazolines (2009–2020)

Recent Advances in the Synthesis of Imidazolines (2009–2020)

Catalytic Enantio‐ and Diastereoselective Mannich Addition of TosMIC to Ketimines

Iridium-catalyzed reductive Ugi-type reactions of tertiary amides

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