1,6‐Conjugate Addition of 1,3‐Dicarbonyl Compounds to para‐Quinone Methides Enabled by Noncovalent N‐Heterocyclic Carbene Catalysis

Abstract

Catalysis with N‐heterocyclic carbenes (NHCs) via substrate activation through noncovalent interactions offers a great opportunity to perform organic transformations. Herein, we demonstrate an efficient catalytic method for the 1,6‐conjugate addition of 1,3‐dicarbonyl compounds to para‐quinone methides (p‐QMs) using NHCs as Brønsted‐base catalysts. The method is applicable to a wide range of functionalized substrates with respect to both 1,3‐diketones and p‐QMs. An initial study using chiral NHCs provides information on the feasibility of developing a catalytic enantioselective variant of this reaction.

Stereoselective Synthesis of Tri- and Tetrasubstituted Olefins via 1,6-Additions of Diazo Compounds and Their Precursors to p-Quinone Methides

“…KOH/MeCN at room temperature, surprisingly gave the same product that was obtained from diazoester 6 and p -QM 1 , that is, tetrasubstituted olefin 7a in comparable yield but different E / Z ratio. Even though addition of 1,3-dicarbonyl compounds to p -QM 1 to form 1,6-adducts of type 10a is well-established in the literature, − the formation tetrasubstituted olefin 7a via 1,6-addition of active methylene compounds is not reported, to the best of our knowledge. Inspired by these results, several tetrasubstituted olefins have been synthesized by this alternative method under KOH/MeCN conditions in varying yields and selectivities as described below (Scheme ).…”

Scandium(III)‐Catalysed Decarboxylative Addition of β‐Ketoacids to para‐Quinone Methides: Evidence for 1,6‐Addition and Base‐Assisted Decarboxylation Tandem Process

“…But surprisingly, the catalytic conjugate addition reactions of p ‐QMs became prevalent very recently, especially those examples of reacting with 1,3‐dicarbonyl compounds are rare . Generally, these reactions can be classified into different catalytic system: (1) Fan's chiral ammonium phase‐transfer catalyst and Cao & Wu's amide‐phosphonium salt as bifunctional phase‐transfer catalyst;, (2) Guin's NHCs and Anand's carbenes as brønsted base catalysts;,, (3) Wang's Mn(OAc) 3 ⋅H 2 O/ferrocenyl triazole ligands catalytic system . To the best of our knowledge, there is no report of catalytic decarboxylative addition to p ‐QMs by using β ‐ketoacids as 1,3‐dicarbonyl nucleophiles.…”

β‐Keto Amides: A Jack‐of‐All‐Trades Building Block in Organic Chemistry

“…In 2018, Guin and co‐workers [151] reported an asymmetric 1,6‐addition of 341 to p ‐quinone methides 342 using a chiral NHC 342 as the catalyst (Scheme 67). The addition was limited to secondary β ‐keto amides with an acidic N–H that could form either hydrogen bonding interaction (Mode A ) or chiral ion‐pair between the enolate and the NHC catalyst (Mode B ).…”