Tetraalkylammonium Salts as Hydrogen‐Bonding Catalysts

Abstract

Although the hydrogen-bonding ability of the α-hydrogens on tetraalkylammonium salts is often discussed in the chemistry of phase-transfer catalysts, the catalysis that utilizes the hydrogenbond donor properties of tetraalkylammonium salts remains unknown. In the present work, we demonstrated hydrogen-bonding catalysis with newly designed tetraalkylammonium salt catalysts in Mannich-type reactions. Both the structure and the hydrogenbonding ability of the new ammonium salts were investigated via Xray diffraction analysis and NMR titration studies.Tetraalkylammonium salts are recognized as representative organocatalysts, [1] and are often used as phase-transfer catalysts for the activation of anionic nucleophiles through the formation of an ion pair with an ammonium cation.[2] Although the structures of tetraalkylammonium salts are commonly expressed as 1a shown in Figure 1, the actual ionic structures are discussed differently. [3][4][5] The positive charge of ammonium salts delocalized on the α-hydrogen atoms, which are known to interact with an anionic counterion through hydrogen bonding, as shown in 1A. Reetz proved the delocalization of the positive charge in tetraalkylammonium salts by X-ray crystal analysis of tetrabutylammonium salts such as tetrabutylammonium enolate and phenoxide.[3] Furthermore, DFT calculations support the delocalized structures of ammonium salts, which include chiral ammonium salts. [4,5] The interaction between α-hydrogens on the chiral tetraalkylammonium salt catalyst and the enolate oxygen was thought to be important in the transition-state model of asymmetric phase-transfer reactions.[5] However, despite the interesting hydrogen-bonding ability of the α-hydrogens on tetraalkylammonium salts, the catalysis that could utilize such properties is, to the best of our knowledge, still unknown. Herein, we report a new dimension of tetraalkylammonium salt as a hydrogen-bonding catalyst that utilizes the characteristic properties of the α-hydrogens on the catalyst. To realize the efficient hydrogen-bonding catalysis of a tetraalkylammonium salt, we designed a new tetraalkylammonium salt, 2, which was readily prepared via the methylation of a commercially available 2,6-piperidinecarboxylate, 3 (Scheme 1). The ammonium salt 2 possesses carboxylate groups at the α-carbon, which enhance the hydrogen-bonding ability of the α-hydrogens. Furthermore, the six-membered structure of the piperidine backbone fixes the acidic α-hydrogens to a position that is appropriate for bidentate binding to an anionic group. [7] Scheme 1. Design and synthesis of a new tetraalkylammonium salt for use as a hydrogen-bonding catalyst.To obtain structural information of newly prepared tetraalkylammonium salts 2, we performed an X-ray diffraction COMMUNICATIONanalysis of ammonium iodide 2a (Figure 2). [8] The crystal structure of 2a provided important structural information. As expected, the hydrogen-bonding interactions between the α-hydrogens and the counteranion (I -) were clearly observed, and the iodid...

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