+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Insights into N-Heterocyclic Carbene-Catalyzed Oxidative α-C(sp 3 )-H Activation of Aliphatic Aldehydes and Cascade [2 + 2] Cycloaddition with Ketimines

Insights into N-Heterocyclic Carbene-Catalyzed Oxidative α-C(sp 3 )-H Activation of Aliphatic Aldehydes and Cascade [2 + 2] Cycloaddition with Ketimines

Journal of Organic Chemistry 84(10): 6117-6125

Predicting the chemoselectivity of [2 + 2] cyclizations is an important challenge in organic chemistry. Herein, we provided a valuable case for this issue. Density functional theory calculations were performed to systematically study the possible mechanisms and origin of selectivities for the N-heterocyclic carbene (NHC)-catalyzed oxidative α-C(sp3)-H activation of aliphatic aldehydes and the cascade [2 + 2] cycloaddition with ketimines. The [2 + 2] cycloaddition of azolium enolate intermediates to the C═N bond, rather than the C═O bond of ketimine, is revealed to be determined by chemo- and stereoselectivity. By comparing the energy gap between the frontier molecular orbitals (FMOs) of the two reacting parts involved in the [2 + 2] cycloaddition transition states, we propose a new strategy to determine the origin of the reaction chemoselectivity. Moreover, the local nucleophilic index can efficiently predict the active site of ketimines. Further analyses illustrate that NHC can increase the nucleophilicity of aldehydes and the acidity of the α-C(sp3)-H bond, and 3,3',5,5'-tetra- tert-butyl diphenoquinone (DQ) acts as an oxidant and promotes α-C(sp3)-H bond deprotonation. This work is useful not only for understanding the NHC-catalyzed oxidative [2 + 2] annulation but also for developing new applications of the FMO theory in organocatalytic cyclizations.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 066715845

Download citation: RISBibTeXText

PMID: 31012584

DOI: 10.1021/acs.joc.9b00295

Related references

Insights into the N-Heterocyclic Carbene (NHC)-Catalyzed Oxidative γ-C(sp 3 )-H Deprotonation of Alkylenals and Cascade [4 + 2] Cycloaddition with Alkenylisoxazoles. Journal of Organic Chemistry 83(15): 8543-8555, 2018

N-heterocyclic-carbene-catalyzed asymmetric oxidative hetero-Diels-Alder reactions with simple aliphatic aldehydes. Angewandte Chemie 51(49): 12330-3, 2012

N-heterocyclic carbene catalyzed enantioselective α-fluorination of aliphatic aldehydes and α-chloro aldehydes: synthesis of α-fluoro esters, amides, and thioesters. Angewandte Chemie 54(2): 660-663, 2015

Enantioselective [2+2] annulation of simple aldehydes with isatin-derived ketimines via oxidative N-heterocyclic carbene catalysis. Chemical Communications 53(24): 3430-3433, 2017

A computational study on the N-heterocyclic carbene-catalyzed Csp(2)-Csp(3) bond activation/[4+2] cycloaddition cascade reaction of cyclobutenones with imines: a new application of the conservation principle of molecular orbital symmetry. Physical Chemistry Chemical Physics 18(29): 19933-19943, 2016

Oxidative enantioselective α-fluorination of aliphatic aldehydes enabled by N-heterocyclic carbene catalysis. Angewandte Chemie 54(2): 656-659, 2015

N-Heterocyclic Carbene-Catalyzed Oxidative Amidation of Aldehydes with Amines. Advanced Synthesis & Catalysis 357(6): 1199-1203, 2015

N-heterocyclic carbene-catalyzed aerobic oxidative direct esterification of aldehydes with organoboronic acids. Chemistry An Asian Journal 7(5): 872-875, 2012

Oxidative N-heterocyclic carbene catalyzed stereoselective annulation of simple aldehydes and 5-alkenyl thiazolones. Chemical Communications 51(38): 8134-8137, 2015

N-Heterocyclic Carbene-Catalyzed δ-Carbon LUMO Activation of Unsaturated Aldehydes. Journal of the American Chemical Society 137(17): 5658-5661, 2015

N-heterocyclic carbene catalyzed oxidative coupling of aldehydes with carbodiimides under aerobic conditions: efficient synthesis of N-acylureas. Organic Letters 15(9): 2088-2091, 2013

N-Heterocyclic Carbene Catalyzed Oxidative Coupling of Alkenes/α-Bromoacetophenones with Aldehydes: A Facile Entry to α,β-Epoxy Ketones. Angewandte Chemie 54(47): 14150-3, 2015

N-Heterocyclic Carbene-Catalyzed Oxidative Annulations of α,β-Unsaturated Aldehydes with Hydrazones: Selective Synthesis of Optically Active 4,5-Dihydropyridazin-3-ones and Pyridazin-3-ones. Journal of Organic Chemistry 80(12): 6350-6359, 2015

Enantioselective N-heterocyclic carbene catalyzed aza-benzoin reaction of enals with activated ketimines. Angewandte Chemie 52(22): 5803-5806, 2013

Ruthenium(II)/N-heterocyclic carbene catalyzed [3+2] carbocyclization with aromatic N-H ketimines and internal alkynes. Angewandte Chemie 52(26): 6681-6684, 2013