Hydrogen‐Bonding Catalysis of Tetraalkylammonium Salts in an Aza‐Diels–Alder Reaction

Abstract

A piperidine-derived tetraalkylammonium salt with a non-coordinating counteranion worked as an effective hydrogen-bonding catalyst in an aza-Diels-Alder reaction of imines and a Danishefsky diene. The hydrogen-bonding interaction between the ammonium salt and an imine was observed as part of a (1) H NMR titration study.

N+-C-H···O Hydrogen bonds in protein-ligand complexes

“…C-H groups that are covalently bound to a cationic nitrogen atom (N + -C-H), C-H···O hydrogen bonds may become as strong as heteroatom-hydrogen bonds, which could be important for molecular recognition 12–19 . For example, N + -C-H···Y hydrogen bonds are likely to be involved in the substrate recognition of tetraalkylammonium-based catalysts 20,21 , and the ligand/substrate recognition in receptors/enzymes may be controlled by N + -C-H···O hydrogen bonds (Supplementary Fig. S1A,B) 22–24 .…”

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

“…In light of the recent studies by Shirakawa and Maruoka [50–51], we propose that catalysts L13 could act not only through Coulombic interactions, but also as hydrogen bond donors. While various factors including Coulombic interactions between the pyridinium (or ammonium) salt and the chloride undoubtedly play an important role in promoting substrate ionization and chloride complexation, the provided X-ray data are consistent with L13 acting as hydrogen bond donors (Scheme 10).…”

“…The existence of alpha C–H hydrogen bonds has also been invoked in the computational studies rationalizing the outcome of various asymmetric phase-transfer reactions [46–49]. However, despite these developments until recently [50–51] the use of tetraalkylammonium salts as hydrogen bond donor catalysts has not been explored.…”

“…A variety of ammonium salts ( L7–L10 ) including chiral cinchonidine derivatives L7 and catalyst L10 were found to promote the reaction in low-to-good yields albeit with no enantioselectivity. Although it is perhaps one of the first examples of utilizing tetralkylammonium salts as hydrogen bond donor catalysts, the authors provided no mechanistic proposal for the catalytic activity of L7–L10 , and the activation of the imine by the formation of a C–H···N hydrogen bond was proposed later by Maruoka and Shirakawa [50–51]. …”

“…In 2016 Maruoka and Shirakawa followed up the aforementioned studies by demonstrating that tetraalkylammonium salts L5 , L6 , L11 and L12 as well as TBAI could activate imines toward aza-Diels–Alder reaction with Danishefsky’s diene (Scheme 9) [51]. Catalyst L11 was selected as the catalyst of choice due to its simplicity and activity.…”