N-Heterocyclic Carbene-Catalyzed Conjugate Additions of Alcohols

Abstract

An efficient intermolecular conjugate addition of alcohols to activated alkenes catalyzed by N-heterocyclic carbenes has been developed. With 5 mol % of the free carbene derived from IMes•HCl, unsaturated ketones and esters are competent substrates and a variety of primary and secondary alcohols can be employed as the nucleophile. No oligomerization is observed under these mild conditions for effective hydroalkoxylation. In addition to reactions with activated alkenes, IMes catalyzes the formation of vinyl ethers through the 1,4-addition of alcohols to ynones and promotes tandem conjugate addition/Michael cascade reactions. Preliminary data supports a Brønsted base mechanism with the free carbene.

Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates

“…Confirming our initial hypothesis, we found that strong Brønsted base NHCs, such as N,N-dialkylimidazolium-generated NHCs, neither catalysed nor generated appreciable conversion for this reaction. This result is in sharp contrast to previous reports that used NHCs as Brønsted bases for both oxy-and carbo-Micheal addition reactions 45,46 . Those reports primarily used N-alkyl imidazolium-derived NHCs because they are strongly basic.…”

“…A recent study on NHCcatalysed oxy-Michael addition showed that facial discrimination was poor with popular chiral-NHC scaffolds; only 11% enantioselectivity was achieved for an intramolecular addition reaction, possibly as a result of a loosely stacked catalyst/substrate ion pair (Fig. 2b) 45 . In a separate report on carbo-Michael addition, strongly basic NHCs showed excellent catalytic activity.…”

Catalytic kinetic resolution of a dynamic racemate: highly stereoselective β-lactone formation by N-heterocyclic carbene catalysis

“…50–61 These unique Lewis bases have been used to generate acyl anion, 62–76 homoenolate, 77–94 and enolate equivalents, 41,95–105 as well as promote hydroacylation 106–111 and an exciting variety of non– Umpolung processes. 112–115 These carbene-catalyzed processes have been used to access numerous challenging compound classes with high levels of diastereo- and enantioselectivities. With all of the different reaction manifolds accessed through carbene catalysis, it is interesting to note that before our 2012 report, there had been no previous examples in the literature of NHCs facilitating a DKR.…”

N‐Heterocyclic Carbene‐Catalyzed Michael Additions of 1,3‐Dicarbonyl Compounds

“…In the past decade, catalysis by N-heterocyclic carbenes (NHCs) has received considerable attention, [6] and we have recently reported the serendipitous discovery of the excellent organocatalytic activity of N,N-diaryl-1,3-imidazol(in)-2-ylidenes in intramolecular Michael additions of 1,3-dicarbonyl compounds, and its application to the stereoselective synthesis of spiro compounds (Scheme 1). [7] Herein, we report our studies on the scope of the NHC-catalyzed Michael addition [8] of 1,3-dicarbonyl derivatives and related compounds, some applications to stereoselective organocatalytic domino carbocyclization reactions, and the results of early mechanistic investigations.…”