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. [6] Figure 1. Structures of tetraalkylammonium salt.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...

Maximizing Coordination Capsule–Guest Polar Interactions in Apolar Solvents Reveals Significant Binding

“…Surmising that even stronger binding was possibly being masked by tight ion-pairing,o ther capsule salts, 1·4 X, were then prepared either directly from the relevent Pd II source (X À = BF 4 À )orbyadding excess NaX or KX to 1·4 OTf( X À = PF 6 À ,S bF 6 À ,B ArF À [BArF = B-(3,5-(CF 3 ) 2 C 6 H 3 ) 4 À ]). [12] Non-capsule salts were removed by exploiting the low solubility of 1·4 Xi ne ither methanol or water, while 19 FNMR spectroscopy confirmed anion metathesis.I nterestingly,c omparing the 1 HNMR spectra of 1·4 X (see Figures S3, S27 in the Supporting Information) indicates that the stronger coordinating anions,O Tf À and BF 4 À in particular,are likely to reside within the cavity of the capsule, with internal signals H a and H e being notably deshielded by up to 0.2 ppm in the case of both 1·4 OTfa nd 1·4 BF 4 . [13] The affinity of 1 4+ for the different anions was also qualitatively observed using ESI-MS; 1·4 OTfexhibited dominant 2 + and 3 + charge states with two and one associated anions, respectively,w hile the "naked" 1 4+ was the major ion with 1·4 BArF (Figures S28-32).…”

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 2015 Shirakawa and Maruoka demonstrated that ammonium salts L5 and L6 could serve as effective catalysts for isoquinolinium and pyridinium salt Mannich reactions (Scheme 7) [50]. Catalysts L5 and L6 were selected due to their conformational rigidity that results in a better alignment of alpha C–H groups, relatively high polarization of the alpha C–H bonds due to the presence of electron-withdrawing ester functionalities, and ease of preparation (1–2 steps from commercially available piperidine).…”