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Review
. 2018 Apr 27:2:1-26.
doi: 10.1016/j.isci.2018.03.006. Epub 2018 Apr 5.

N-Heterocyclic-Carbene-Catalyzed Domino Reactions via Two or More Activation Modes

Xiang-Yu Chen  1 , Sun Li  1 , Fabrizio Vetica  1 , Mukesh Kumar  1 , Dieter Enders  2
Affiliations
Review

N-Heterocyclic-Carbene-Catalyzed Domino Reactions via Two or More Activation Modes

Xiang-Yu Chen et al. iScience. .

Abstract

Organocatalytic domino processes have become a rapidly growing area of research. N-heterocyclic carbenes (NHCs) have emerged as powerful organocatalysts for various transformations and continue to have widespread application. In the last decade, domino reactions catalyzed by NHCs have seen significant progress since the different activation modes could be successfully combined in one process. The most attractive features of these domino sequences include the readily available catalysts and substrates, the simple operational procedures, and the rapid assembly of complex molecular scaffolds with excellent levels of stereocontrol under mild reaction conditions. This review covers the advances in NHC-catalyzed domino reactions by focusing on the reaction scope, limitations, and mechanism with a close attention to the features of the reaction substrates.

Keywords: Organic Chemistry Methods; Organic Synthesis; Stereochemistry.

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Figures

None
Graphical abstract
Scheme 1
Scheme 1
Summary of Classic Reactions via NHC Catalysis (A) Reactions via the Breslow intermediates. (B) Reactions via azolium enolates. (C) Reactions via homoenolate equivalents. (D) Reactions via azolium dienolates. (E) Reactions via acyl azoliums. (F) Reactions via α,β-unsaturated acyl azolium intermediates.
Scheme 2
Scheme 2
Domino Reactions via Breslow Intermediate and Enolate Activation Modes
Scheme 3
Scheme 3
Classification of NHC-Catalyzed Domino Reactions via Two or More Activation Modes (A) Domino reactions via homoenolate-enolate activation modes. (B) Domino reactions via α,β-unsaturated acyl azolium-enolate activation modes. (C) Domino reactions via dienolate-enolate activation modes.
Scheme 4
Scheme 4
The Michael Acceptors for Domino Reactions via the Homoenolate-Enolate Activation Modes
Scheme 5
Scheme 5
Domino a3-d3 Umpolung/Michael/Aldol/Lactonization/Decarboxylation Reaction
Scheme 6
Scheme 6
Proposed Catalytic Cycle for the Domino a3-d3 Umpolung/Michael/Aldol/Lactonization/Decarboxylation Reaction
Scheme 7
Scheme 7
Asymmetric Domino a3-d3 Umpolung/Michael/Aldol/Lactonization/Decarboxylation Reaction (A) Bode's work. (B) Scheidt's work.
Scheme 8
Scheme 8
Domino a3-d3 Umpolung/Michael/Aldol/Lactonization Reaction
Scheme 9
Scheme 9
Domino a3-d3 Umpolung/Michael/Aldol/Esterification Reaction
Scheme 10
Scheme 10
Domino a3-d3 Umpolung/Michael/Aldol/Dehydration/Lactonization Reaction
Scheme 11
Scheme 11
Domino a3-d3 Umpolung/Michael/Aldol/Dehydration/Lactamization Reaction
Scheme 12
Scheme 12
Domino a3-d3 Umpolung/Michael/Aldol/Lactamization Reaction
Scheme 13
Scheme 13
Domino a3-d3 Umpolung/Michael/Mannich/Lactamization Reaction (A) Bode's work. (B) Chi's work.
Scheme 14
Scheme 14
Domino a3-d3 Umpolung/Michael/Mannich/Lactamization Reaction of Isatin-Derived Enals
Scheme 15
Scheme 15
Domino a3-d3 Umpolung/Michael/Michael/Esterification Reaction
Scheme 16
Scheme 16
Proposed Mechanism for Domino a3-d3 Umpolung/Michael/Michael/Esterification Reaction
Scheme 17
Scheme 17
Domino a3-d3 Umpolung/Michael/Michael/Esterification Between Benzodienones and α,β-Unsaturated Aldehydes
Scheme 18
Scheme 18
Domino a3-d3 Umpolung/Michael/Michael/Michael/Lactonization Reaction
Scheme 19
Scheme 19
Domino a3-d3 Umpolung/Michael/Michael/Lactonization Reaction of 2-Aroylvinylcinnamaldehydes
Scheme 20
Scheme 20
Domino Homo-Aldol/Michael/Lactonization Reaction
Scheme 21
Scheme 21
Proposed Mechanism for the Domino Reactions via α,β-Unsaturated Acyl Azolium Enolate Activation Mode
Scheme 22
Scheme 22
Classification of NHC-Catalyzed Domino Reactions via α,β-Unsaturated Acyl Azolium and Enolate Activation Modes
Scheme 23
Scheme 23
Domino Michael/Aldol/Lactonization Reaction
Scheme 24
Scheme 24
Domino Michael/Aldol/Lactonization Reaction between Ketone-Malonates and α,β-Unsaturated Aldehydes
Scheme 25
Scheme 25
Domino Michael/Aldol/Lactonization/Decarboxylation Reaction between Ketone-Malonates and α,β-Unsaturated Aldehydes
Scheme 26
Scheme 26
Domino aza-Michael/Aldol/Lactonization Reaction
Scheme 27
Scheme 27
Domino Michael/Aldol/Lactonization/Decarboxylation Reaction
Scheme 28
Scheme 28
Domino Michael/Aldol/Lactonization/Decarboxylation Reaction between Silyl Dienol Ethers and α,β-Unsaturated Acid Fluorides
Scheme 29
Scheme 29
Domino Reactions of Enol Esters via α,β-Unsaturated Acyl Azolium and Enolate Activation Modes
Scheme 30
Scheme 30
Domino Michael/Aldol/Lactonization/Decarboxylation/Aromatization Reaction
Scheme 31
Scheme 31
Domino Reactions via 1,6-Addition to the α,β-Unsaturated Acyl Azoliums
Scheme 32
Scheme 32
Domino Michael/Aldol/Lactonization/Decarboxylation between Diketones and α,β−Unsaturated Aldehydes
Scheme 33
Scheme 33
Domino Michael/Michael/Lactonization Reaction of Alkynyl Aldehydes
Scheme 34
Scheme 34
Domino Michael/Michael/Lactonization Reaction of α,β-Unsaturated Aldehydes and Bifunctional Malonates
Scheme 35
Scheme 35
Domino Aza-Michael/Michael/Lactonization Reaction
Scheme 36
Scheme 36
Domino Sulfa-Michael/Michael/Lactonization Reaction
Scheme 37
Scheme 37
Domino Michael/Mannich/Lactamization Reaction
Scheme 38
Scheme 38
Domino Michael/SN2/Esterification Reaction
Scheme 39
Scheme 39
Domino Michael/Michael/Lactonization Reaction via Bifunctional α,β-Unsaturated Acyl Azoliums
Scheme 40
Scheme 40
Domino Michael/Michael/Lactonization/Decarboxylation Reaction via Bifunctional α,β-Unsaturated Acyl Azoliums
Scheme 41
Scheme 41
Domino Michael/Aldol/Lactonization/Decarboxylation/Aromatization Reaction
Scheme 42
Scheme 42
N-Heterocyclic-Carbene-Catalyzed [4 + 2] Cycloaddition of Enals via a Double Vinylogous Michael Addition
Scheme 43
Scheme 43
Proposed Catalytic Cycle for the Domino Michael/Acylation/Transesterification/Dehydration Reaction
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