NHC-catalyzed Reactions Of Enals Research Articles

N-Heterocyclic Carbene-Catalyzed Michael-Michael-Lactonization Cascade for the Enantioselective Synthesis of Tricyclic δ-Lactones.

Enantioselective synthesis of tricyclic δ-lactones with three contiguous stereocenters has been demonstrated by the N-heterocyclic carbene (NHC)-catalyzed functionalization of benzylic C(sp3)-H bonds. The NHC-catalyzed reaction of enals with dinitrotoluene derivatives under oxidative conditions proceeds via the chiral α,β-unsaturated acylazoliums and produces the δ-lactones in good yields and excellent diastereoselectivity and enantioselectivity. This mild and atom-economic cascade reaction takes place in a Michael/Michael/lactonization sequence and tolerates a broad range of functional groups.

Diastereoselective synthesis of cyclopentanone-fused spirooxindoles by N-heterocyclic carbene-catalyzed homoenolate annulation with isatilidenes

NHC-catalyzed reaction of enals with N-substituted isatilidenes resulting in the diastereoselective synthesis of cyclopentanone-fused spirooxindoles proceeding via the homoenolate equivalent intermediates is reported.

NHC-Catalyzed Reaction of Enals with Hydroxy Chalcones: Diastereoselective Synthesis of Functionalized Coumarins

The N-heterocyclic carbene-catalyzed annulation of enals with 2'-hydroxy chalcones afford cyclopentane-fused coumarin derivatives with an excellent level of diastereocontrol. The reaction tolerates a broad range of functional groups; 25 examples are given, and a preliminary mechanistic investigation is provided.

Controlled β-protonation and [4+2] cycloaddition of enals and chalconesvia N-heterocyclic carbene/acid catalysis: toward substrate independent reaction control

A substrate-independent selective generation of enolates over homoenolate equivalents in NHC-catalyzed reactions of enals and chalcones is disclosed. Acid co-catalysts play vital roles in control of the reaction pathways, allowing for individual access to diverse products from identical substrates.

The effect of the N-mesityl group in NHC-catalyzed reactions

The majority of N-heterocyclic carbene catalyzed reactions of α-functionalized aldehydes, including annulations, oxidations, and redox reactions, occur more rapidly with N-mesityl substituted NHCs. In many cases, no reaction occurs with NHCs lacking ortho-substituted aromatics. By careful competition studies, catalyst analogue synthesis, mechanistic investigations, and consideration of the elementary steps in NHC-catalyzed reactions of enals, we have determined that the effect of the N-mesityl group is to render the initial addition of the NHC to the aldehyde irreversible, thereby accelerating the formation of the Breslow intermediate. These studies rationalize the experimentally observed catalyst preference for all classes of NHC-catalyzed reactions of aldehydes and provide a roadmap for catalyst selection and design.

NHC-catalyzed reaction of enals with unactivated enones: substituent effect on the formation of 1 : 1 and 1 : 2 adducts

It has been found for the first time that the imidazole carbene-catalyzed reaction of α,β-unsaturated aldehydes with unactivated enones gives two kinds of pyranones, 1 : 1 and 1 : 2 adducts, instead of cyclopentenes and cyclopentanones. The ratio of the two products was determined by the substituent effect of the enones, not by a molar ratio of the starting materials in general. Moreover, a longer reaction period caused the formation of another 1 : 2 adduct, which was derived from the 1 : 1 pyranones initially formed.

Vinylogous Umpolung with Nitrosobenzene

A one-pot procedure to N-PMP-protected β-amino acid esters by a NHC-catalyzed reaction of enals and nitrosobenzene, followed by an acid-catalyzed esterification and a Bamberger-like rearrangement of the intermediate N-phenylisoxazolidin-5-ones is reported. Several aryl- and alkyl-substituted α,β-unsaturated aldehydes were tested. Substrates with different functional groups are also suitable for this transformation. This new methodology was applied to the synthesis of N-PMP-protected β-DOPA. Furthermore a preliminary study of an enantioselective modification of this protocol is presented.