Amide-Phosphonium Salt as Bifunctional Phase Transfer Catalyst for Asymmetric 1,6-Addition of Malonate Esters to para-Quinone Methides

Abstract

Asymmetric 1,6-addition of malonates to para-quinone methides has been developed by using amide-phosphonium salts derived from easily available chiral α-amino acids as bifunctional phase transfer catalysts. Stabilized para-quinone methides with various substituents on the phenyl ring were reacted with diphenyl malonates to give functionalized diaryl methines in excellent yields and high to excellent ee's. Furthermore, to show the utility of this methodology, a gram scale synthesis of an 1,6-addition adduct and its further elaboration into the key intermediate for synthesis of GPR40 agonists were also described.

Enantioselective Rauhut–Currier‐Type 1,6‐Conjugate Addition of Methyl Vinyl Ketone to para‐Quinone Methides

“…We envisioned that p ‐QMs could be a second Michael acceptor in an RC reaction (Scheme b). In the aforementioned pieces of work,,,– p ‐QMs could be activated by chiral Brønsted acid through an intermolecular H‐bonding interaction, resulting in remote stereocontrol. Notably, phosphines are also elegant catalysts for the RC reaction .…”

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.…”

Bifunctional Ion Pair Catalysts from Chiral α‐Amino Acids

“…Over the past few years, para ‐quinone methides have emerged as excellent electrophiles for enantioselective 1,6‐addition reaction, which provide a significant method for generating chiral diaryl methines . In 2016, Wu and co‐workers firstly applied amide‐phosphonium salts Q into asymmetric 1,6‐conjugate addition reactions between para ‐quinone methides 44 and diphenyl malonates 45 . A large range of substituted para ‐quinone methides derived from aryl aldehydes were well tolerated to afford the phenols 46 in high yields and ee values.…”