Prediction of NHC-catalyzed chemoselective functionalizations of carbonyl compounds: a general mechanistic map

• Published in: Chemical science (Cambridge) Vol. 11; no. 27; pp. 7214 - 7225
• Main Authors: Li, Xue, Xu, Jun, Li, Shi-Jun, Qu, Ling-Bo, Li, Zhongjun, Chi, Yonggui Robin, Wei, Donghui, Lan, Yu
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 21.07.2020; The Royal Society of Chemistry
• Subjects: Carbonyl compounds; Carbonyls; Cartesian coordinates; Chemical reactions; Chemistry; Oxidizing agents
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d0sc01793k

Generally, N-heterocyclic carbene (NHC) complexed with carbonyl compounds would transform into several important active intermediates, i.e. , enolates, Breslow intermediates, or acylazolium intermediates, which act as either a nucleophile (Nu) or an electrophile (E) to react with the other E/Nu partner. Hence, the key to predicting the origin of chemoselectivity is to compute the activity ( i.e. , electrophilic index ω for E and nucleophilic index N for Nu) and stability of the intermediates and products, which are suggested in a general mechanistic map of these reactions. To support this point, we selected and studied different cases of the NHC-catalyzed reactions of carbonyl compounds in the presence of a base and/or an oxidant, in which multiple possible pathways involving acylazolium, enolate, Breslow, and α,β-unsaturated acylazolium intermediates were proposed and a novel index ω + N of the E and Nu partners was employed to exactly predict the energy barrier of the chemoselective step in theory. This work provides a guide for determining the general principle behind organocatalytic reactions with various chemoselectivities, and suggests a general application of the reaction index in predicting the chemoselectivity of the nucleophilic and electrophilic reactions. A novel index ω + N can be used to predict the chemoselectivity according to the general NHC-catalyzed reaction mechanism.