H-Bond Mediated Phase-Transfer Catalysis: Enantioselective Generating of Quaternary Stereogenic Centers in β-Keto Esters

Abstract

In this work, we would like to present the development of a highly optimized method for generating the quaternary stereogenic centers in β-keto esters. This enantioselective phase-transfer alkylation catalyzed by hybrid Cinchona catalysts allows for the efficient generation of the optically active products with excellent enantioselectivity, using only 1 mol% of the catalyst. The vast majority of phase-transfer catalysts in asymmetric synthesis work by creating ionic pairs with the nucleophile-attacking anionic substrate. Therefore, it is a sensible approach to search for new methodologies capable of introducing functional groups into the precursor’s structure, maintaining high yields and enantiomeric purity.

1. Introduction

The generation of a quaternary stereogenic center in organic molecules has for many years been a demanding challenge that fits into the theme of organic catalysis, even in the asymmetric variant [1,2,3,4,5,6]. The development of enantioselective synthetic methods, including organocatalysis, has led to the possibility of obtaining synthetic mimetics of compounds of natural origin [7,8,9,10,11]. The presence of a quaternary carbon center in a molecule is very often a key factor in the biological activity of natural products or drugs [12,13,14,15,16,17].

Among the possible substrates, β-dicarbonyl compounds, especially β-ketoesters, undoubtedly stand out [18,19,20]. These compounds can undergo numerous organic transformations (including alkylation) to form a quaternary stereogenic center with a variety of substituents, allowing further organic transformations and various post-functionalization processes [21,22,23]. Optically active α-alkylated β-dicarbonyl compounds are common building blocks of many natural compounds and pharmaceuticals.

Importantly, this type of derivatives can also provide an important direction for the synthesis of unnatural β-amino acids and other important building blocks [24,25,26]. Despite these important advantages, asymmetric synthesis using organocatalysts is still a major challenge for synthetic chemists. Therefore, the development of so-called “green” synthetic methods remains an important achievement [27,28]. To date, asymmetric α-alkylation reactions of β-ketoesters have been catalyzed mainly by palladium and enamine catalysts [29,30,31].

Among organocatalytic methods, phase transfer catalytic (PTC) reactions represent one of the simplest and most efficient tools for enantio-differentiation synthesis [32,33,34,35]. The most commonly used chiral catalysts of natural origin are ammonium salts, derivatives of Cinchona alkaloids, among others, due to their availability and economic considerations [36,37,38,39]. Moreover, it has been repeatedly shown that the use of large substituents on the nitrogen atom of the quinuclidinium ring improves the properties of such a catalyst [40,41].

To date, there are few examples in the literature of the use of PTC in the alkylation of β-ketoesters, which was initially limited mainly to phosphonium salts. One of the first reports dates back to the late 20th century [42]. The diamide catalysts synthesized by Manabe showed limited catalytic properties, with enantiomeric excesses as high as 50% ee. A few years later, Maruoka [43] and coworkers used quaternary ammonium catalysts built on a binaphthalene platform. These highly specialized catalysts showed high activity in the alkylation reactions of cyclic β-ketoesters as well as in the Michael reaction. The first examples of the use of Cinchona derivatives as catalysts in β-keto esters alkylation were presented by the Dehmlow [44] and Chinchilla [45] groups, but in both cases the maximum enantiomeric excess oscillated around 50% ee. To improve the enantiomeric excess, Kim [46] and coworkers synthesized catalysts containing phenyl rings substituted with tert-butyl groups. This type of substituent provides high steric hindrance. On the other hand, N-substituted Cinchona catalysts allowing high enantiomeric excesses >90% ee were reported in 2019 [47]. These catalysts have been used in alkylation reactions of β-ketoesters and β-ketoamides. Recently, our team developed and commercialized a family of novel hybrid quaternary ammonium salts based on Cinchona alkaloids [48,49,50] which are capable of catalyzing a range of organic reactions, for example, the quaternization of β-ketoesters by introducing a chlorine atom into the product structure [51]. The catalysts of this type are based on the structure of alkaloids of natural origin, which perfectly fits into the trends of the so-called “green chemistry”. Moreover, their advantage over the catalysts presented earlier in the literature consists in the trivial two-step synthesis, which allows to obtain pure catalysts in crystalline form at any scale with total excellent yields. After the successful application of our catalysts in chlorination, we decided to test other reactions and the choice fell on the alkylation of cyclic β-ketoesters, namely various indanone esters and cyclopentanones.

2. Results

For several years, we have been presenting a new family of hybrid Cinchona catalysts which, in addition to the standard properties presented by phase-transfer catalysts, possess hydrogen bond donors in their structure which efficiently supports the generation of high enantiomeric excess (Figure 1) [48,49]. In addition, the use of aromatic substituents with appropriate geometry makes it possible to create other non-covalent interactions (e.g., π-π stacking) which favors the preorganization of the substrate [39]. Thus, we have presented a family of catalysts effective in the reactions of alkylation of glycine derivatives [48], epoxidation of α,β-unsaturated ketones [50], and recently also in α-chlorination of β-keto esters [51]. In this paper, we present the development of our methodology for another reaction, namely, the alkylation of β-keto esters with the formation of a quaternary stereogenic center.

First, using catalyst L which showed the highest efficiency in our previous studies, we optimized the β-keto ester 1a alkylation procedure. We screened several bases in toluene/CHCl₃ [7:3, v/v] mixture (Table 1, entries 1–6). In almost all cases, the product was received in quantitative yield. Using solid bases, as well as 50% aqueous solutions, provided similar results, however the best ones occurred for solid KF. Next, we screened the impact of the solvent (Table 1, entries 7–11). As in our previous papers, the best results occurred for the toluene/CHCl₃ [7:3, v/v] mixture. It is worth mentioning that the reaction enantioselectivity was improved to 72% ee when the temperature was decreased to 5 °C. Moreover, the catalyst loading equal to only 1 mol% was enough to effectively carry out the reaction. Finally, the optimal conditions are the reaction carried out in the toluene/CHCl₃ mixture [7:3, v/v], 1 mol% of catalyst, 5 °C, 2 eq of base (KF), and 1.2 eq of the alkylating agent.

Next, using the model β-keto ester 1a, we studied the modification of the catalyst structure, in particular the substituent at the amide group. The only catalyst in our list with an aliphatic substituent A (adamantyl ring) allowed us to obtain product 2a with an enantiomeric excess of 60% ee (Table 2, entry 1). The simplest of the catalysts, with phenyl substituent B, as well as the ortho-substituted catalysts C–E did not increase the enantiomeric excess (55–61% ee) (Table 2, entries 3–5). The situation was similar after the introduction of both electron-donating methoxy groups (catalysts G–I, 31–42% ee, Table 1, entries 8–10), as well as in the presence of electron-withdrawing groups (catalyst J with –NO₂ group, 56% ee and 2,3,4-trifluorophenyl K, 57% ee). Slightly better enantiomeric excesses were obtained for compounds with biphenyl substituent—F (64% ee, Table 1, entry 6). In all cases, we observed complete conversion of the substrate within 3–7 h.

Then, we decided to check the activity of catalysts constructed with a quinine core. This procedure led to a series of reactions in which we were able to obtain higher enantiomeric excesses. The catalyst with the biphenyl substituent adjacent to the amide group L allowed us to obtain the product with 68% ee (Table 2, entry 13). Compounds substituted in ortho-position of the aromatic ring with α- and β-naphthyl rings M and N gave 73% and 70% ee, respectively. The highest catalytic activity was obtained for the catalyst substituted with quinoline in ortho-position O (80% ee, Table 2, entry 16). The use of catalysts with a quinine platform allowed us to shorten the reaction time to 3–4 h. At the same time, it is worth noting that in all presented cases the reactions occurred with almost quantitative yields (96–99%).

After the experiments that led to the determination of the best catalyst, we decided to check the efficiency of the reactions by increasing the steric hindrance of the ester group (isopropyl, tert-butyl) and changing the geometric structure of the substrate (indanone, cyclopentanone), using catalyst O. In reactions with indanone derivatives 1a–c, we observed that increasing the steric hindrance favors the improvement of the enantiomeric excess, with the highest values for the tert-butyl 1c (91% ee) ester (Table 3, entry 3). The same occurred for cyclopentanone derivatives 1d and 1e: increased steric hindrance resulted in higher asymmetric induction (Table 3, entries 4 and 5). We also performed an additional comparative experiment for the methyl ester using a quinidine catalyst. This procedure allowed for an almost complete reversal of the enantiomeric excess (80 vs. –84% ee).

In the next stage, we decided to investigate the influence of the nature of the electrophile used in the reaction. In this series of reactions, we used indanone tert-butyl ester 1c as the optimal β-keto ester substrate. The model benzyl bromide as well as isomers of methyl benzyl bromide allowed us to obtain products 2c and 3–6 with 89–91% ee (Table 4, entries 1–4). The presence of chloride in the electrophile molecule 6 did not significantly change the enantiomeric excess (88% ee, Table 4, entry 5).

To gain a better insight into the complexing process, we decided to conduct computational studies indicating a plausible intermediate state (Figure 2). After the first step, namely the deprotonation of the substrate, the complex of phase-transfer catalyst and enolate is formed. The nucleophilic substrate can be stabilized by two intermolecular hydrogen bonds: with amide function of the catalyst and in addition with the hydroxyl group. A key element determining the high enantioselectivity is the quinoline ring which blocks the re-face of the enolate. These interactions synergistically stabilize the complex and further increase the selectivity of the underlying nucleophile attack. Conducted computational studies are in agreement with the obtained results. The lowest energy conformation of the complex of catalyst with enolate was found after conducting a conformational search analysis and selected conformers with the lowest energies which were then optimized without any constrains at DFT/M06-2X/6-31G(d) level of theory using program Spartan’18 Parallel Suite [52,53,54,55,56].

3. Materials and Methods

3.1. Reagents and General Methods

All reagents were used as received. The solvents were dried by distillation over the appropriate drying agents. All solvents were obtained from common suppliers and used as received. TLC was carried out on Merck Kieselgel F254 plates. Melting points were determined using a Boëtius M HMK hot-stage apparatus and were uncorrected. The NMR spectra were recorded on a Bruker Mercury 400 MHz and Bruker 500 MHz and Varian 600 MHz instruments (see SI). Chemical shifts are reported in ppm (δ) and are set to the solvent residue peak. J coupling constants values are re-ported in Hz. Mass spectral analyses were performed with the ESI-TOF technique on a Mariner mass spectrometer from PerSeptive Biosystem. The enantiomeric excesses of products were determined by chiral HPLC analysis using Chiralcel AD-H column (see Supplementary Materials).

Amide-based Cinchona catalysts A–L were prepared according to our previous procedure [48]. Catalysts M-O have not been previously reported. Alkylated indanone and cyclopentanone derivatives 2a–e and 4 are known from the literature and their analytical data fully matched those reported previously in the literature [43,45,47].

General procedure for the asymmetric alkylation of β-keto esters 1a–e. A mixture of the appropriate β-keto ester 1a–e (0.2 mmol), catalyst (0.002 mmol), and KF (0.4 mmol) was stirred in toluene/CHCl₃ [7:3, v/v] for 30 min. Subsequently, the mixture was cooled to 5 °C and alkylating agent (0.24 mmol) was added in one portion. The reaction was mixed for 4 h. Then, the mixture was filtered through a short pad of silica and eluted using hexane/ethyl acetate [8:2, v/v]. The organic solvents were evaporated under reduced pressure to obtain a pure product 2a–e and 3–6 in the reported yields and enantiopurities.

3.2. Synthetic Procedures

3.2.1. Synthesis of (1S,2S,4S,5R)-5-Ethenyl-2-[(R)-hydroxy(7-methoxyquinolin-4-yl)methyl]-1-({[2-(naphthalen-2-yl)phenyl]carbamoyl}methyl)-1-azabicyclo [2.2.2]octan-1-ium bromide (M)

Following the literature procedure [48] and using the corresponding bromoamide (1.0 g, 2.9 mmol), the catalyst M (1.9 g, 2.9 mmol, 97%) was obtained as colorless powder (m.p. 122–123 °C). ¹H NMR (400 MHz, DMSO-d₆): δ 10.21 (s, 1H), 8.77 (d, J = 4.2 Hz, 1H), 7.98–7.90 (m, 3H), 7.68 (d, J = 6.6 Hz, 2H), 7.60–7.28 (m, 10H), 6.63 (s, 1H), 6.56 (s, 1H), 5.91 (s, 1H), 5.82 (s, 1H), 5.71–5.42 (m, 1H), 5.12 (d, J = 13.9 Hz, 1H), 5.00 (d, J = 14,1 Hz) 4.82 (t, J = 14.9 Hz, 1H), 4.43–4.21 (m, 1H), 4.37–4.22 (m, 2H), 4.06 (dd, J = 15.9, 7.6 Hz, 1H), 3.74 (s, 3H), 3.12 (t, J = 11.3 Hz, 2H), 2.68 (s, 1H), 2.59 (s, 1H), 1.98 (s, 2H), 1.88–1.76 (m, 2H). ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 163.2, 157.9, 150.3, 147.2, 145.4, 143.7, 143.3, 138.0, 136.4, 134.3, 131.4, 130.7, 128.4, 128.2, 127.7, 126.2, 125.9, 125.4, 122.2, 121.5, 120.2, 115.5, 100.9, 65.7, 63.0, 59.6, 58.7, 56.5, 56.0, 36.6, 25.3, 24.7, 21.2. HRMS ESI (m/z): calc for C₃₈H₃₈N₃O₃ [M]⁺: 584.2913, found: 584.2919.

3.2.2. Synthesis of (1S,2S,4S,5R)-5-Ethenyl-2-[(R)-hydroxy(7-methoxyquinolin-4-yl)methyl]-1-({[2-(naphthalen-1-yl)phenyl]carbamoyl}methyl)-1-azabicyclo [2.2.2]octan-1-ium bromide (N)

Following the literature procedure [48] and using the corresponding bromoamide (1.0 g, 2.9 mmol), the catalyst N (1.8 g, 2.8 mmol, 95%) was obtained as colorless powder (m.p. 135–136 °C). ¹H NMR (500 MHz, DMSO-d₆): δ 10.22 (d, J = 6.7 Hz, 1H), 8.79–8.75 (m, 1H), 7.98–7.92 (m, 3H), 7.72–7.66 (m, 2H), 7.61–7.27 (m, 10H), 6.61 (d, J = 3.5 Hz, 1H), 5.91 (s, 1H), 5.82 (s, 1H), 5.70–5.43 (m, 1H), 5.10 (d, J = 13.9 Hz, 1H), 4.98 (d, J = 12.6 Hz, 1H), 4.82 (dd, J = 20.7, 13.8 Hz, 1H), 4.44–4.17 (m, 1H), 4.37–4.21 (m, 2H), 4.06 (dd, J = 16.1, 10.8 Hz, 1H), 3.74 (s, 3H), 3.32–3.07 (m, 2H), 2.66 (s, 1H), 2.58 (s, 1H), 2.05–1.94 (m, 2H), 1.84–1.77 (m, 2H). ¹³C{¹H} NMR (126 MHz, DMSO-d₆): δ 163.6, 163.4, 157.9, 147.3, 143.7, 143.4, 137.7, 135.8, 134.3, 133.4, 131.4, 131.2, 128.3, 127.9, 127.5, 127.1, 127.0, 126.8, 126.2, 125.8, 125.5, 125.2, 125.0, 122.1, 120.3, 115.4, 101.0, 65.6, 63.6, 63.1, 59.3, 58.7, 56.3, 56.0, 36.5, 25.2, 24.7, 21.2. HRMS ESI (m/z): calc for C₃₈H₃₈N₃O₃ [M]⁺: 584.2913, found: 584.2915.

3.2.3. (1S,2S,4S,5R)-5-Ethenyl-2-[(R)-hydroxy(7-methoxyquinolin-4-yl)methyl]-1-({[2-(quinolin-8-yl)phenyl]carbamoyl}methyl)-1-azabicyclo [2.2.2]octan-1-ium bromide (O)

Following the literature procedure [48] and using the corresponding bromoamide (1.0 g, 2.9 mmol), the catalyst O (1.9 g, 2.9 mmol, 98%) was obtained as colorless powder (m.p. 150–151 °C). ¹H NMR (600 MHz, DMSO-d₆): δ 10.01 (s, 1H), 8.79 (d, J = 4.5 Hz, 2H), 8.41 (d, J = 6.3 Hz, 1H), 8.02 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 9.2 Hz, 1H), 7.76–7.63 (m, 4H), 7.53–7.47 (m, 3H), 7.45–7.37 (m, 3H), 6.65 (s, 1H), 5.96–5.88 (m, 2H), 5.21 (dd, J = 17.6, 14.0 Hz, 2H), 4.41 (d, J = 15.7 Hz, 1H), 4.30 (t, J = 9.1 Hz, 1H), 4.26 (t, J = 9.2 Hz, 1H), 4.04–3.95 (m, 1H), 3.73 (s, 4H), 3.44 (s, 1H), 3.13 (d, J = 9.6 Hz, 1H), 2.70 (d, J = 7.2 Hz, 1H), 2.01 (d, J = 10.2 Hz, 1H), 1.89–1.75 (m, 3H), 0.89–0.83 (m, 1H). ¹³C{¹H} NMR (151 MHz, DMSO-d₆): δ 163.1, 157.9, 150.3, 147.2, 145.5, 143.7, 143.3, 136.5, 136.4, 134.4, 131.3, 130.9, 128.4, 128.2, 127.6, 126.3, 125.7, 122.1, 121.5, 120.4, 117.1, 101.6, 66.0, 63.8, 60.1, 59.0, 56.5, 56.0, 37.1, 26.2, 22.8, 20.4. HRMS ESI (m/z): calc for C₃₇H₃₇N₄O₃ [M]⁺: 585.2866, found: 585.2859.

3.2.4. Methyl 2-Benzyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2a)

Following the general procedure, the product 2a (55 mg, 0.2 mmol, 99%, 80% ee) was obtained as colorless oil. ¹H NMR (500 MHz, CDCl₃) δ 7.72 (d, J = 7.7 Hz, 1H), 7.51 (t, J = 7.4 Hz, 1H), 7.35–7.29 (m, 2H), 7.19–7.09 (m, 5H), 3.70 (s, 3H), 3.61 (d, J = 17.3 Hz, 1H), 3.47 (d, J = 14.0 Hz, 1H), 3.28 (d, J = 14.0 Hz, 1H), 3.15 (d, J = 17.3 Hz, 1H). ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 202.2, 171.3, 153.3, 136.5, 135.4, 135.3, 130.1, 128.4, 127.8, 127.0, 126.4, 124.8, 61.8, 53.0, 39.9, 35.5. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 11.7 min, t_minor = 9.0 min. Analytical data fully matched those reported previously in the literature [45,47].

3.2.5. Propan-2-yl 2-Benzyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2b)

Following the general procedure, the product 2b (60 mg, 0.2 mmol, 98%, 85% ee) was obtained as colorless oil. ¹H NMR (400 MHz, CDCl₃) δ 7.73 (d, J = 7.7 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.32 (dd, J = 12.8, 7.4 Hz, 2H), 7.19–7.10 (m, 5H), 5.09–4.96 (m, 1H), 3.61 (d, J = 17.3 Hz, 1H), 3.48 (d, J = 14.1 Hz, 1H), 3.27 (d, J = 14.1 Hz, 1H), 3.15 (d, J = 17.3 Hz, 1H), 1.18 (dd, J = 6.3, 2.4 Hz, 6H). ¹³C{¹H} NMR (101 MHz, CDCl₃) 202.4, 170.3, 153.4, 136.7, 135.4, 135.3, 130.1, 128.3, 127.6, 126.8, 126.3, 124.7, 69.5, 61.9, 39.7, 35.6, 21.7, 21.6. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 14.4 min, t_minor = 15.8 min. Analytical data fully matched those reported previously in the literature [47].

3.2.6. Tert-Butyl 2-Benzyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2c)

Following the general procedure, the product 2c (64 mg, 0.2 mmol, 99%, 91% ee) was obtained as colorless oil. For the reaction using 1 mmol of 1c (232 mg), the product 2c was obtained in an amount of 319 mg (1.0 mmol, 99%). ¹H NMR (500 MHz, CDCl₃) δ 7.72 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.4 Hz, 1H), 7.32 (dd, J = 14.0, 7.3 Hz, 2H), 7.20–7.10 (m, 5H), 3.57 (d, J = 17.1 Hz, 1H), 3.44 (d, J = 14.1 Hz, 1H), 3.27 (d, J = 14.1 Hz, 1H), 3.12 (d, J = 17.1 Hz, 1H), 1.38 (s, 9H). ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 202.8, 169.9, 153.5, 137.0, 135.6, 135.1, 130.1, 128.3, 127.6, 126.8, 126.2, 124.6, 82.2, 62.6, 39.5, 35.8, 27.9. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 6.1 min, t_minor = 5.5 min. Analytical data fully matched those reported previously in the literature [47].

3.2.7. Methyl 1-Benzyl-2-oxocyclopentane-1-carboxylate (2d)

Following the general procedure, the product 2d (46 mg, 0.2 mmol, 99%, 61% ee) was obtained as colorless oil. ¹H NMR (600 MHz, CDCl₃) δ 7.21–7.17 (m, 2H), 7.17–7.13 (m, 1H), 7.05 (d, J = 7.0 Hz, 2H), 3.65 (s, 3H), 3.14 (d, J = 13.8 Hz, 1H), 3.04 (d, J = 13.8 Hz, 1H), 2.38–2.27 (m, 2H), 2.01–1.94 (m, 1H), 1.92–1.86 (m, 1H), 1.85–1.78 (m, 1H), 1.57–1.49 (m, 1H). ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 215.0, 171.5, 136.6, 130.3, 128.5, 127.0, 61.6, 52.8, 39.3, 38.5, 31.8, 19.6. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 7.1 min, t_minor = 8.1 min. Analytical data fully matched those reported previously in the literature [47].

3.2.8. Tert-Butyl 1-Benzyl-2-oxocyclopentane-1-carboxylate (2e)

Following the general procedure, the product 2e (53 mg, 0.2 mmol, 96%, 74% ee) was obtained as colorless oil. ¹H NMR (500 MHz, CDCl₃) δ 7.20–7.15 (m, 2H), 7.15–7.11 (m, 1H), 7.07 (d, J = 6.9 Hz, 2H), 3.05 (s, 2H), 2.32–2.24 (m, 2H), 1.92–1.77 (m, 3H), 1.53–1.45 (m, 1H), 1.36 (s, 9H). ¹³C{¹H} NMR (126 MHz, CDCl₃): δ 215.5, 170.5, 137.1, 130.5, 128.4, 126.8, 82.1, 62.1, 38.9, 38.4, 32.1, 28.0, 19.6. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 8.2 min, t_minor = 9.6 min. Analytical data fully matched those reported previously in the literature [43].

3.2.9. Tert-butyl(2R)-2-[(2-methylphenyl)methyl]-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (3)

Following the general procedure, the product 3 (66 mg, 0.2 mmol, 98%, 90% ee) was obtained as colorless oil. ¹H NMR (500 MHz, CDCl₃) δ 7.77 (d, J = 7.6 Hz, 1H), 7.54 (t, J = 7.1 Hz, 1H), 7.35 (t, J = 7.9 Hz, 2H), 7.12–6.98 (m, 4H), 3.71 (d, J = 17.1 Hz, 1H), 3.58 (d, J = 15.3 Hz, 1H), 3.19 (d, J = 15.3 Hz, 1H), 2.99 (d, J = 17.0 Hz, 1H), 2.28 (s, 3H), 1.36 (s, 9H). ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 203.0, 170.0, 153.7, 137.1, 135.9, 135.2, 130.4, 128.9, 127.6, 126.6, 126.3, 126.0, 124.7, 82.2, 62.3, 36.1, 35.6, 27.8, 20.3. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 9.6 min, t_minor = 8.6 min. HRMS ESI (m/z): calc for C₂₂H₂₄O₃Na [M + Na]⁺: 359.1623, found: 359.1615.

3.2.10. Tert-Butyl 2-[(3-Methylphenyl)methyl]-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (4)

Following the general procedure, the product 4 (65 mg, 0.2 mmol, 97%, 91% ee) was obtained as colorless oil. ¹H NMR (400 MHz, CDCl₃) δ 7.73 (d, J = 7.7 Hz, 1H), 7.54–7.49 (m, 1H), 7.33 (dd, J = 14.5, 7.4 Hz, 2H), 7.06 (t, J = 7.5 Hz, 1H), 6.99–6.92 (m, 3H), 3.57 (d, J = 17.2 Hz, 1H), 3.43 (d, J = 14.1 Hz, 1H), 3.19 (d, J = 14.1 Hz, 1H), 3.11 (d, J = 17.2 Hz, 1H), 2.24 (s, 3H), 1.39 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 202.7, 169.8, 153.5, 137.8, 137.0, 135.6, 135.1, 130.9, 128.2, 127.5, 127.5, 127.1, 126.3, 124.6, 82.2, 62.7, 39.5, 35.8, 27.9, 21.5. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 7.9 min, t_minor = 7.2 min. HRMS ESI (m/z): calc for C₂₂H₂₄O₃Na [M + Na]⁺: 359.1623, found: 359.1613. Analytical data fully matched those reported previously in the literature [45].

3.2.11. Tert-Butyl 2-[(4-Methylphenyl)methyl]-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (5)

Following the general procedure, the product 5 (65 mg, 0.2 mmol, 98%, 89% ee) was obtained as colorless oil. ¹H NMR (500 MHz, CDCl₃) δ 7.73 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.3 Hz, 1H), 7.32 (dd, J = 15.2, 7.5 Hz, 2H), 7.04 (d, J = 7.9 Hz, 2H), 6.98 (d, J = 7.9 Hz, 2H), 3.54 (d, J = 17.2 Hz, 1H), 3.40 (d, J = 14.2 Hz, 1H), 3.22 (d, J = 14.2 Hz, 1H), 3.11 (d, J = 17.2 Hz, 1H), 2.24 (s, 3H), 1.38 (s, 9H). ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 202.8, 169.9, 153.6, 136.3, 135.6, 135.1, 133.9, 130.0, 129.0, 127.5, 126.3, 124.6, 82.1, 62.7, 39.1, 35.7, 27.9, 21.1. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 10.8 min, t_minor = 13.2 min. HRMS ESI (m/z): calc for C₂₂H₂₄O₃Na [M + Na]⁺: 359.1623, found: 359.1621.

3.2.12. Tert-Butyl 2-[(4-Chlorophenyl)methyl]-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (6)

Following the general procedure, the product 6 (71 mg, 0.2 mmol, 97%, 88% ee) was obtained as colorless oil. ¹H NMR (500 MHz, CDCl₃) δ 7.72 (d, J = 7.7 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 7.36–7.31 (m, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 3.54 (d, J = 17.2 Hz, 1H), 3.37 (d, J = 14.1 Hz, 1H), 3.25 (d, J = 14.2 Hz, 1H), 3.06 (d, J = 17.1 Hz, 1H), 1.37 (s, 9H). ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 202.6, 169.8, 153.3, 135.5, 135.4, 135.3, 132.7, 131.5, 128.5, 127.7, 126.3, 124.7, 82.4, 62.3, 38.7, 35.8, 27.9. HPLC-separation conditions: Chiralcel AD-H, 20 °C, 254 nm, hexane/iPrOH [98:2, v/v], 0.8 mL/min; t_major = 14.5 min, t_minor = 11.0 min. HRMS ESI (m/z): calc for C₂₁H₂₁ClO₃Na [M + Na]⁺: 379.1077, found: 379.1085.

Author Contributions

Conceptualization, P.N.; methodology, P.N. and M.M.; validation, P.N. and M.M.; formal analysis, P.N. and P.G.; investigation, P.N., M.M. and P.G.; resources, J.J.; data curation, P.N.; writing—original draft preparation, P.N.; writing—review and editing, P.N. and J.J.; visualization, P.N.; supervision, J.J.; project administration, J.J.; funding acquisition, J.J. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by 2018/29/B/ST5/01366 (J.J.) project, funded by Poland’s National Science Center (NCN).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Not applicable.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures and Tables

Figure 1. Cinchona phase-transfer catalysts A–O.

Figure 2. Model of a possible intermediate state for the reaction.

Table 1

Optimization of the reaction conditions for the alkylation of β-keto ester 1a with phase-transfer catalyst L ^a.

[Image omitted. Please see PDF.]
Entry	Solvent	Base	T (°C)	Yield b (%)	eec (%)
1	PhMe/CHCl3 (7/3)	K2CO3	25	99	64
2	PhMe/CHCl3 (7/3)	50%aq K2CO3	25	99	62
3	PhMe/CHCl3 (7/3)	KF	25	99	67
4	PhMe/CHCl3 (7/3)	50%aq KF	25	99	64
5	PhMe/CHCl3 (7/3)	Na2CO3	25	95	65
6	PhMe/CHCl3 (7/3)	50%aq Na2CO3	25	94	61
7	PhMe	KF	25	99	67
8	m-Xylene	KF	25	99	66
9	CH2Cl2	KF	25	99	66
10	CHCl3	KF	25	99	65
11	PhMe/CHCl3 (7/3)	KF	10	99	71
12	PhMe/CHCl3 (7/3)	KF	5	99	72

^a Unless otherwise specified, the reactions were performed with 1a (1 equiv.), BnBr (1.25 equiv.), phase-transfer catalyst L (1 mol%), and base (2 equiv.). ^b Yields shown are of isolated products. ^c Determined by chiral HPLC (Chiralcel AD-H column).

Table 2

Screening of phase-transfer catalysts A–O using substrate 1a ^a.

Entry	Catalyst		Time (h)	Yield b (%)		eec (%)
1	A		5	99		60
2	B		6	98		55
3	C		5	99		52
4	D		5	99		60
5	E		5	99		61
6	F		4	99		64
7	G		5	98		31
8	H		6	96		49
9	I		7	98		42
10	J		7	97		56
11	K		6	98		57
12	L		4	99		68
13	M		4	99		70
14	N		4	99		73
15	O	O’	3	99	99	80	−84

^a Unless otherwise specified, the reactions were performed with 1a (1 equiv.), BnBr (1.25 equiv.), phase-transfer catalyst (1 mol%), and base (2 equiv.). ^b Yields shown are of isolated products. ^c Determined by chiral HPLC (Chiralcel AD-H column).

Table 3

Screening of β-keto esters 1a–e ^a.

[Image omitted. Please see PDF.]
Entry	Substrate	Yield b [%]	eec [%]
1	[Image omitted. Please see PDF.]	99	80
2	[Image omitted. Please see PDF.]	98	85
3	[Image omitted. Please see PDF.]	99	91
4	[Image omitted. Please see PDF.]	99	61
5	[Image omitted. Please see PDF.]	96	74

^a Unless otherwise specified, the reactions were performed with appropriate β-keto ester (1 equiv.), BnBr (1.25 equiv.), phase-transfer catalyst O (1 mol%), and base (2 equiv.). ^b Yields shown are of isolated products. ^c Determined by chiral HPLC (Chiralcel AD-H column).

Table 4

Screening of alkylating agents ^a.

[Image omitted. Please see PDF.]
Entry	Substrate	Yield b (%)	ee c (%)
1	[Image omitted. Please see PDF.]	99	91
2	[Image omitted. Please see PDF.]	98	90
3	[Image omitted. Please see PDF.]	97	91
4	[Image omitted. Please see PDF.]	98	89
5	[Image omitted. Please see PDF.]	98	88

^a Unless otherwise specified, the reactions were performed with 1c (1 equiv.), appropriate alkylating agent (1.25 equiv.), phase-transfer catalyst O (1 mol%), and base (2 equiv.). ^b Yields shown are of isolated products. ^c Determined by chiral HPLC (Chiralcel AD-H column).

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules27082508/s1: Copies of ¹H and ¹³C NMR spectra of compounds synthesized, chromatograms of enantioenriched mixtures.

References

1. Corey, E.J.; Guzman-Perez, A. The Catalytic Enantioselective Construction of Molecules with Quaternary Carbon Stereocenters. Angew. Chem. Int. Ed.; 1998; 37, pp. 388-401. [DOI: https://dx.doi.org/10.1002/(SICI)1521-3773(19980302)37:4<388::AID-ANIE388>3.0.CO;2-V]

2. Christoffers, J.; Mann, A. Enantioselective Construction of Quaternary Stereocenters. Angew. Chem. Int. Ed.; 2001; 40, pp. 4591-4597. [DOI: https://dx.doi.org/10.1002/1521-3773(20011217)40:24<4591::AID-ANIE4591>3.0.CO;2-V]

3. Wu, G.; Xu, H.; Liu, Z.; Liu, Y.; Yang, X.; Zhang, X.; Huang, Y. Asymmetric Organocatalysis Combined with Palladium Catalysis: Synergistic Effect on Enantioselective Mannich/α-Allylation Sequential Reactions of Pyrazolones in Constructing Vicinal Quaternary Stereocenters. Org. Lett.; 2019; 21, pp. 7708-7712. [DOI: https://dx.doi.org/10.1021/acs.orglett.9b02440] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31545618]

4. Sansinenea, E.; Martinez, E.F.; Ortiz, A. Organocatalytic Synthesis of Chiral Spirooxindoles with Quaternary Stereogenic Centers. Eur. J. Org. Chem.; 2020; 2020, pp. 5101-5118. [DOI: https://dx.doi.org/10.1002/ejoc.202000470]

5. Wang, K.; Yu, J.; Shao, Y.; Tang, S.; Sun, J. Forming All-Carbon Quaternary Stereocenters by Organocatalytic Aminomethylation: Concise Access to β2,2-Amino Acids. Angew. Chem. Int. Ed.; 2020; 59, pp. 23516-23520. [DOI: https://dx.doi.org/10.1002/anie.202009892] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32902091]

6. Yu, S.-J.; Zhu, Y.-N.; Ye, J.-L.; Huang, P.-Q. A versatile approach to functionalized cyclic ketones bearing quaternary carbon stereocenters via organocatalytic asymmetric conjugate addition of nitroalkanes to cyclic β-substituted α,β-Enones. Tetrahedron; 2021; 84, 132005. [DOI: https://dx.doi.org/10.1016/j.tet.2021.132005]

7. Vetica, F.; Chauhan, P.; Dochain, S.; Enders, D. Asymmetric organocatalytic methods for the synthesis of tetrahydropyrans and their application in total synthesis. Chem. Soc. Rev.; 2017; 46, pp. 1661-1674. [DOI: https://dx.doi.org/10.1039/C6CS00757K]

8. Xie, X.; Huang, W.; Peng, C.; Han, B. Organocatalytic Asymmetric Synthesis of Six-Membered Carbocycle-Based Spiro Compounds. Adv. Synth. Catal.; 2018; 360, pp. 194-228. [DOI: https://dx.doi.org/10.1002/adsc.201700927]

9. Lavios, A.; Sanz-Marco, A.; Vila, C.; Gonzalo, B.; Pedro, J.R. Asymmetric Organocatalytic Synthesis of aza-Spirocyclic Compounds from Isothiocyanates and Isocyanides. Eur. J. Org. Chem.; 2021; 2021, pp. 2268-2284. [DOI: https://dx.doi.org/10.1002/ejoc.202100232]

10. Parella, R.; Jakkampudi, S.; Zhao, J.C.-G. Recent Applications of Asymmetrisc Organocatalytic Methods in Total Synthesis. ChemistrySelect; 2021; 6, pp. 2252-2280. [DOI: https://dx.doi.org/10.1002/slct.202004196]

11. Tu, M.-S.; Chen, K.-W.; Wu, P.; Zhang, Y.-C.; Liu, X.-Q.; Shi, F. Advances in organocatalytic asymmetric reactions of vinylindoles: Powerful access to enantioenriched indole derivatives. Org. Chem. Front.; 2021; 8, pp. 2643-2672. [DOI: https://dx.doi.org/10.1039/D0QO01643H]

12. Xu, P.-W.; Yu, J.-S.; Chen, C.; Cao, Z.-Y.; Zhou, F.; Zhou, J. Catalytic Enantioselective Construction of Spiro Quaternary Carbon Stereocenters. ACS Catal.; 2019; 9, pp. 1820-1882. [DOI: https://dx.doi.org/10.1021/acscatal.8b03694]

13. Zhu, T.; Liu, Y.; Smetankova, M.; Zhuo, S.; Chi, Y.R.; Zhu, T.; Mou, C.; Chai, H.; Jin, Z. Carbene-Catalyzed Desymmetrization and Direct Construction of Arenes with All-Carbon Quaternary Chiral Center. Angew. Chem. Int. Ed.; 2019; 58, pp. 15778-15782. [DOI: https://dx.doi.org/10.1002/anie.201910183]

14. Wang, Z.; Liu, J. All-carbon [3 + 2] cycloaddition in natural product synthesis. Beilstein J. Org. Chem.; 2020; 16, pp. 3015-3031. [DOI: https://dx.doi.org/10.3762/bjoc.16.251] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33363670]

15. Wang, Z. Construction of all-carbon quaternary stereocenters by catalytic asymmetric conjugate addition to cyclic enones in natural product synthesis. Org. Chem. Front.; 2020; 7, pp. 3815-3841. [DOI: https://dx.doi.org/10.1039/D0QO00763C]

16. Wang, Z.; Yang, Z.-P.; Fu, G.C. Quaternary stereocentres via catalytic enantioconvergent nucleophilic substitution reactions of tertiary alkyl halides. Nat. Chem.; 2021; 13, pp. 236-242. [DOI: https://dx.doi.org/10.1038/s41557-020-00609-7]

17. Xin, Z.; Wang, H.; He, H.; Gao, S. Recent advances in the total synthesis of natural products bearing the contiguous all-carbon quaternary stereocenters. Tetrahedron; 2021; 71, 153029. [DOI: https://dx.doi.org/10.1016/j.tetlet.2021.153029]

18. Benetti, S.; Romagnoli, R.; De Risi, C.; Spalluto, G.; Zanirato, V. Mastering. beta.-Keto Esters. Chem. Rev.; 1995; 95, pp. 1065-1114. [DOI: https://dx.doi.org/10.1021/cr00036a007]

19. Kallepu, S.; Sanjeev, K.; Chegondi, R.; Mainkar, P.S.; Chandrasekhar, S. Benzyne Insertion onto β-Keto Esters of Polycyclic Natural Products: Synthesis of Benzo Octacyclo Scaffolds. Org. Lett.; 2018; 20, pp. 7121-7124. [DOI: https://dx.doi.org/10.1021/acs.orglett.8b03070]

20. Kazmierczak, J.C.; Cargnelutti, R.; Barcellos, T.; Silveira, C.C.; Schumacher, R.F. Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions. Beilstein J. Org. Chem.; 2021; 17, pp. 234-244. [DOI: https://dx.doi.org/10.3762/bjoc.17.24]

21. Corral-Bautista, F.; Mayr, H. Quantification of the Nucleophilic Reactivities of Cyclic β-Keto Ester Anions. Eur. J. Org. Chem.; 2015; 2015, pp. 7594-7601. [DOI: https://dx.doi.org/10.1002/ejoc.201501107]

22. Wang, Y.; Wang, S.; Gao, Q.; Li, L.; Zhi, H.; Zhang, T.; Zhang, J. Transition-metal, organic solvent and base free α-hydroxylation of β-keto esters and β-keto amides with peroxides in water. Tetrahedron; 2019; 75, pp. 3856-3863. [DOI: https://dx.doi.org/10.1016/j.tet.2019.06.011]

23. Wang, Y.-F.; Jiang, Z.-H.; Chu, M.-M.; Qi, S.-S.; Yin, H.; Han, H.-T.; Xu, D.-Q. Asymmetric copper-catalyzed fluorination of cyclic β-keto esters in a continuous-flow microreactor. Org. Biomol. Chem.; 2020; 18, pp. 4927-4931. [DOI: https://dx.doi.org/10.1039/D0OB00588F] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32573633]

24. Wang, Y.; Mo, M.; Zhu, K.; Zheng, C.; Zhang, H.; Wang, W.; Shao, Z. Asymmetric synthesis of syn-propargylamines and unsaturated β-amino acids under Bronsted base catalysis. Nat. Commun.; 2015; 6, 8544. [DOI: https://dx.doi.org/10.1038/ncomms9544]

25. Zhang, D.; Chen, X.; Zhang, R.; Yao, P.; Wu, Q.; Zhu, D. Development of β-amino acid dehydrogenase for the synthesis of β-amino acids via reductive amination of β-keto acids. ACS Catal.; 2015; 5, pp. 2220-2224. [DOI: https://dx.doi.org/10.1021/cs5017358]

26. Asano, T.; Moritani, M.; Nakajima, M.; Kotani, S. Chiral lithium binaphtholate for enantioselective amination of acyclic α-alkyl-β-keto esters: Application to the total synthesis of L-carbidopa. Tetrahedron; 2017; 73, pp. 5975-5982. [DOI: https://dx.doi.org/10.1016/j.tet.2017.08.015]

27. Bryliakov, K.P. Catalytic Asymmetric Oxygenations with the Environmentally Benign Oxidants H. Chem. Rev.; 2017; 117, pp. 11406-11459. [DOI: https://dx.doi.org/10.1021/acs.chemrev.7b00167]

28. Tavakolian, M.; Vahdati-Khajeh, S.; Asgari, S. Recent Advances in Solvent-Free Asymmetric Catalysis. ChemCatChem; 2019; 11, pp. 2943-2977. [DOI: https://dx.doi.org/10.1002/cctc.201900354]

29. Trost, B.M.; Sacchi, K.L.; Schroeder, G.M.; Asakawa, N. Intramolecular Palladium-Catalyzed Allylic Alkylation:  Enantio- and Diastereoselective Synthesis of [2.2.2] Bicycles. Org. Lett.; 2002; 4, pp. 3427-3430. [DOI: https://dx.doi.org/10.1021/ol0265766]

30. Nemoto, T.; Fukuda, T.; Matsumoto, T.; Hitomi, T.; Hamada, Y. Enantioselective Construction of All-Carbon Quaternary Stereocenters Using Palladium-Catalyzed Asymmetric Allylic Alkylation of γ-Acetoxy-α,β-unsaturated Carbonyl Compounds. Adv. Synth. Catal.; 2005; 347, pp. 1504-1506. [DOI: https://dx.doi.org/10.1002/adsc.200505149]

31. Zhou, H.; Wang, Y.; Zhang, L.; Cai, M.; Luo, S. Enantioselective Terminal Addition to Allenes by Dual Chiral Primary Amine/Palladium Catalysis. J. Am. Chem. Soc.; 2017; 139, pp. 3631-3634. [DOI: https://dx.doi.org/10.1021/jacs.7b00437] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28238267]

32. Verbicky, J.W., Jr.; O’Neil, E.A. Chiral phase-transfer catalysis. Enantioselective alkylation of racemic alcohols with a nonfunctionalized optically active phase-transfer catalyst. J. Org. Chem.; 1985; 50, pp. 1786-1787. [DOI: https://dx.doi.org/10.1021/jo00210a054]

33. Ooi, T.; Takeuchi, M.; Kameda, M.; Maruoka, K. Practical catalytic enantioselective synthesis of α,α-dialkyl-α-amino acids by chiral phase-transfer catalysis. J. Am. Chem. Soc.; 2000; 122, pp. 5228-5229. [DOI: https://dx.doi.org/10.1021/ja0007051]

34. Arlt, A.; Toyama, H.; Takada, K.; Hashimoto, T.; Maruoka, K. Phase-transfer catalyzed asymmetric synthesis of α,β-unsaturated γ,γ-disubstituted γ-lactams. Chem. Commun.; 2017; 53, pp. 4779-4782. [DOI: https://dx.doi.org/10.1039/C7CC01058C]

35. Sicignano, M.; Rodriguez, R.I.; Capaccio, V.; Borello, F.; Cano, R.; De Riccardis, F.; Bernardi, L.; Diaz-Tendero, S.; Della Sala, G.; Aleman, J. Asymmetric trifluoromethylthiolation of azlactones under chiral phase transfer catalysis. Org. Biomol. Chem.; 2020; 18, pp. 2914-2920. [DOI: https://dx.doi.org/10.1039/D0OB00476F]

36. Woo, S.; Kim, Y.-G.; Lim, B.; Oh, J.; Lee, Y.; Gwon, H.; Nahm, K. Dimeric cinchona ammonium salts with benzophenone linkers: Enantioselective phase transfer catalysts for the synthesis of α-amino acids. RSC Adv.; 2018; 8, pp. 2157-2160. [DOI: https://dx.doi.org/10.1039/C7RA12499F]

37. Hu, B.; Deng, L. Direct Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Esters/Lactones via Umpolung Strategy. J. Org. Chem.; 2019; 84, pp. 994-1005. [DOI: https://dx.doi.org/10.1021/acs.joc.8b02893] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30543752]

38. Wang, J.; Liu, Y.; Wei, Z.; Cao, J.; Liang, D.; Lin, Y.; Duan, H. Synthesis of 4-Azaindolines Using Phase-Transfer Catalysis via an Intramolecular Mannich Reaction. J. Org. Chem.; 2020; 85, pp. 4047-4057. [DOI: https://dx.doi.org/10.1021/acs.joc.9b03025] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32130006]

39. Majdecki, M.; Niedbała, P.; Tyszka-Gumkowska, A.; Jurczak, J. Assisted by Hydrogen-Bond Donors: Cinchona Quaternary Salts as Privileged Chiral Catalysts for Phase-Transfer Reactions. Synthesis; 2021; 53, pp. 2777-2786.

40. Corey, E.J.; Xu, F.; Noe, M.C. A Rational Approach to Catalytic Enantioselective Enolate Alkylation Using a Structurally Rigidified and Defined Chiral Quaternary Ammonium Salt under Phase Transfer Conditions. J. Am. Chem. Soc.; 1997; 119, pp. 12414-12415. [DOI: https://dx.doi.org/10.1021/ja973174y]

41. Zhang, F.-Y.; Corey, E.J. Highly Enantioselective Michael Reactions Catalyzed by a Chiral Quaternary Ammonium Salt. Illustration by Asymmetric Syntheses of (S)-Ornithine and Chiral 2-Cyclohexenones. Org. Lett.; 2000; 2, pp. 1097-1100. [DOI: https://dx.doi.org/10.1021/ol0056527] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10804563]

42. Manabe, K. Synthesis of novel chiral quaternary phosphonium salts with a multiple hydrogen-bonding site, and their application to asymmetric phase-transfer alkylation. Tetrahedron; 1998; 54, pp. 14465-14476. [DOI: https://dx.doi.org/10.1016/S0040-4020(98)00899-0]

43. Ooi, T.; Miki, T.; Taniguchi, M.; Shiraishi, M.; Takeuchi, M.; Maruoka, K. Highly Enantioselective Construction of Quaternary Stereocenters on β-Keto Esters by Phase-Transfer Catalytic Asymmetric Alkylation and Michael Reaction. Angew. Chem. Int. Ed.; 2003; 42, pp. 3796-3798. [DOI: https://dx.doi.org/10.1002/anie.200351469] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12923847]

44. Dehmlow, E.V.; Düttmann, S.; Neumann, B.; Stammler, H.-G. Monodeazacinchona Alkaloid Derivatives: Synthesis and Preliminary Applications as Phase-Transfer Catalysts. Eur. J. Org. Chem.; 2002; 2002, pp. 2087-2093. [DOI: https://dx.doi.org/10.1002/1099-0690(200207)2002:13<2087::AID-EJOC2087>3.0.CO;2-Z]

45. Tarí, S.; Chinchilla, R.; Nájera, C.; Yus, M. Enantioselective alkylation of β-keto esters promoted by dimeric Cinchona-derived ammonium salts as recoverable organocatalysts. Arkivoc; 2011; 7, pp. 116-127. [DOI: https://dx.doi.org/10.3998/ark.5550190.0012.710]

46. Park, E.J.; Kim, M.H.; Kim, Y. Enantioselective Alkylation of β-Keto Esters by Phase-Transfer Catalysis Using Chiral Quaternary Ammonium Salts. J. Org. Chem.; 2004; 69, pp. 6897-6899. [DOI: https://dx.doi.org/10.1021/jo0401772]

47. Wang, Y.; Li, Y.; Lian, M.; Zhang, J.; Liu, Z.; Tang, X.; Yin, H.; Meng, Q. Asymmetric α-alkylation of cyclic β-keto esters and β-keto amides by phase-transfer catalysis. Org. Biomol. Chem.; 2019; 17, pp. 573-584. [DOI: https://dx.doi.org/10.1039/C8OB02669F]

48. Majdecki, M.; Niedbała, P.; Jurczak, J. Amide-Based Cinchona Alkaloids as Phase-Transfer Catalysts: Synthesis and Potential Application. Org. Lett.; 2019; 21, pp. 8085-8090. [DOI: https://dx.doi.org/10.1021/acs.orglett.9b03065]

49. Majdecki, M.; Niedbała, P.; Jurczak, J. Synthesis of C2 Hybrid Amide-Based PTC Catalysts and Their Comparison with Saturated Analogues. ChemistrySelect; 2020; 5, pp. 6424-6429. [DOI: https://dx.doi.org/10.1002/slct.202001012]

50. Majdecki, M.; Tyszka-Gumkowska, A.; Jurczak, J. Highly Enantioselective Epoxidation of α,β-Unsaturated Ketones Using Amide-Based Cinchona Alkaloids as Hybrid Phase-Transfer Catalysts. Org. Lett.; 2020; 22, pp. 8687-8691. [DOI: https://dx.doi.org/10.1021/acs.orglett.0c03272]

51. Majdecki, M.; Grodek, P.; Jurczak, J. Stereoselective α-Chlorination of β-Keto Esters in the Presence of Hybrid Amide-Based Cinchona Alkaloids as Catalysts. J. Org. Chem.; 2020; 86, pp. 995-1001. [DOI: https://dx.doi.org/10.1021/acs.joc.0c02486] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33320665]

52. Wavefunction Inc. I.A. Spartan. 2018; Available online: www.wavefun.com (accessed on 6 March 2022).

53. Zhao, Y.; Truhlar, D.G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: Two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor. Chem. Acc.; 2008; 120, pp. 215-241.

54. Kozuch, S.; Martin, J.M.L. Halogen Bonds: The Reliability of Pure and Hybrid DFT Methods Analysis. J. Chem. Theory Comput.; 2013; 9, pp. 1918-1931. [DOI: https://dx.doi.org/10.1021/ct301064t]

55. Bauzá, A.; Alkorta, I.; Frontera, A.; Elguero, J. On the Reliability of Pure and Hybrid DFT Methods for the Evaluation of Halogen, Chalcogen, and Pnicogen Bonds Involving Anionic and Neutral Electron Donors. J. Chem. Theory Comput.; 2013; 9, pp. 5201-5210. [DOI: https://dx.doi.org/10.1021/ct400818v] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26583427]

56. Hohenstein, E.G.; Chill, S.T.; Sherrill, C.D. Assessment of the Performance of the M05−2X and M06−2X Exchange-Correlation Functionals for Noncovalent Interactions in Biomolecules. J. Chem. Theory Comput.; 2008; 4, pp. 1996-2000. [DOI: https://dx.doi.org/10.1021/ct800308k] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26620472]