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

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 intramol...

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Veröffentlicht in:Chemistry, an Asian journal an Asian journal, 2018-07, Vol.13 (13), p.1710-1718
Hauptverfasser: Li, Xue, Tang, Mingsheng, Wang, Yanyan, Wang, Yang, Li, Zhongjun, Qu, Ling‐Bo, Wei, Donghui
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Sprache:eng
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Zusammenfassung: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. Carbene catalysis: The detailed mechanisms and chemoselectivity of N‐heterocyclic carbene (NHC)‐catalyzed intramolecular cyclization of aldimines via different types of Breslow intermediates for the formation of 2‐(hetero)aryl indole 3‐acetic‐acid derivatives have been investigated by using the DFT method.
ISSN:1861-4728
1861-471X
DOI:10.1002/asia.201800313