N‐Heterocyclic‐Carbene‐Catalyzed Umpolung of Imines

Patra, Aditya Kumar; Mukherjee, Subrata; Das, Tamal; Jain, Sunita; Gonnade, Rajesh G.; Biju, Akkattu T.

doi:10.1002/anie.201611268

Cited by 95 publications

(38 citation statements)

References 68 publications

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“…This term was introduced by D. Seebach and E. J. Corey to refer the inversion of reactivity of acyl carbon atoms in their reactions with electrophiles 2 . Analogous methods based on switching the reactivity of amines 3 , imines [4][5][6] , or carbonyl groups [7][8][9][10][11][12][13] have been developed in recent decades. This approach has played a pivotal role in the design of synthetic procedures, allowing access to target molecules that would be difficult to obtain by classical processes.…”

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confidence: 99%

An umpolung strategy to react catalytic enols with nucleophiles

et al. 2019

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The selective synthesis of α-functionalized ketones with two similar enolizable positions can be accomplished using allylic alcohols and iridium(III) catalysts. A formal 1,3-hydrogen shift on allylic alcohols generates catalytic iridium-enolates in a stereospecific manner, which are able to react with electrophiles to yield α-functionalized ketones as single constitutional isomers. However, the employment of nucleophiles to react with the nucleophilic catalytic enolates in this chemistry is still unknown. Herein, we report an umpolung strategy for the selective synthesis of α-alkoxy carbonyl compounds by the reaction of iridium enolates and alcohols promoted by an iodine(III) reagent. Moreover, the protocol also works in an intramolecular fashion to synthesize 3(2H)-furanones from γ-keto allylic alcohols. Experimental and computational investigations have been carried out, and mechanisms are proposed for both the inter-and intramolecular reactions, explaining the key role of the iodine(III) reagent in this umpolung approach.

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confidence: 99%

An umpolung strategy to react catalytic enols with nucleophiles

et al. 2019

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“…As shown in Figure , Figure , and Figure S9 in the Supporting Information, the energy barriers of the entire mechanisms A, B, C, D, and E are 20.6, 32.8, 27.7, 33.4, and 76.7 kcal mol −1 , respectively, indicating that mechanism A with the formation of the aza‐Breslow intermediate is the most energetically favorable. Such a conclusion is consistent with the fact that the aza‐Breslow intermediate can be observed in experiments. In other words, the AIC mode (associated with mechanism A) would be the main pathway in the NHC‐catalyzed reaction, and mechanism A should be the general principle for this type of reaction.…”

Section: Resultsmentioning

confidence: 99%

Insights into the N‐Heterocyclic Carbene (NHC)‐Catalyzed Intramolecular Cyclization of Aldimines: General Mechanism and Role of Catalyst

Xue

Tang

Wang

et al. 2018

Chemistry An Asian Journal

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One of the most challenging questions in the Lewis base organocatalyst field is how to predict the most electrophilic carbon for the complexation of N-heterocyclic carbene (NHC) and reactant. This study provides a valuable case for this issue. Multiple mechanisms (A, B, C, D, and E) for the intramolecular cyclization of aldimine catalyzed by NHC were investigated by using density functional theory (DFT). The computed results reveal that the NHC energetically prefers attacking the iminyl carbon (AIC mode, which is associated with mechanisms A and C) rather than attacking the olefin carbon (AOC mode, which is associated with mechanisms B and D) or attacking the carbonyl carbon (ACC mode, which is associated with mechanism E) of aldimine. The calculated results based on the different reaction models indicate that mechanism A (AIC mode), which is associated with the formation of the aza-Breslow intermediate, is the most favorable pathway. For mechanism A, there are five steps: (1) nucleophilic addition of NHC to the iminyl carbon of aldimine; (2) [1,2]-proton transfer to form an aza-Breslow intermediate; (3) intramolecular cyclization; (4) the other [1,2]-proton transfer; and (5) regeneration of NHC. The analyses of reactivity indexes have been applied to explain the chemoselectivity, and the general principles regarding the possible mechanisms would be useful for the rational design of NHC-catalyzed chemoselective reactions.

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“…However, it wasn't until 2017 that Biju and Suresh independently reported cycloisomerization of imine 6 to indole 7 [Figure , Eq. (2)] in the first NHC catalyzed reaction involving imine umpolung ,. Subsequently, the aza‐Breslow intermediate has been invoked in the oxidation of imines to amides, and a quinolone synthesis .…”

Section: Figurementioning

confidence: 99%

Enantioselective N‐Heterocyclic Carbene Catalysis that Exploits Imine Umpolung

et al. 2019

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The catalytic umpolung of imines remains an underdeveloped approach to reaction discovery.H erein we report an enantioselective aza-Stetter reaction that proceeds via imine umpolung using N-heterocyclic carbene catalysis.T he reaction proceeds with high levels of enantioselectivity (all ! 96:4 er) and good generality (21 examples). Mechanistic studies are reported and are consistent with turnover-limiting addition of the NHC to the imine. Figure 1. Previously and this work.

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N‐Heterocyclic‐Carbene‐Catalyzed Umpolung of Imines

Cited by 95 publications

References 68 publications

An umpolung strategy to react catalytic enols with nucleophiles

An umpolung strategy to react catalytic enols with nucleophiles

Insights into the N‐Heterocyclic Carbene (NHC)‐Catalyzed Intramolecular Cyclization of Aldimines: General Mechanism and Role of Catalyst

Enantioselective N‐Heterocyclic Carbene Catalysis that Exploits Imine Umpolung

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