Highly para- selective C‒H alkylation of unactivated arenes with α-aryl-α-diazoesters catalyzed by gold(I) immobilized on MCM-41

Abstract

The heterogeneous gold(I)-catalyzed highly para-selective C(sp²)–H bond alkylation of benzene derivatives with α-aryl-α-diazoesters possessing electron-withdrawing substituents on the aryl rings are achieved. The reactions proceed under mild conditions in good to excellent yields by using an MCM-41-anchored diphenylphosphine gold(I) complex [MCM-41-PPh₂-AuOTf] as a recyclable catalyst.

Introduction

Over the past few decades, C–H bond functionalization has been developed into an efficient and straightforward synthetic strategy for the construction of complex molecules.^1–3 In order to make this strategy generally useful in organic synthesis, the development of highly site-selective functionalization of inert C–H bonds has to be addressed. Substituted benzenes exist widely in nature and materials-related fields,^4,5 and they constitute a frequently employed skeleton in small-molecule drugs. ⁶ Therefore, developing site-selective C–H bond functionalization of a benzene ring is highly attractive to the synthetic community and very useful for post-modification of bioactive compounds. Transition-metal-catalyzed, directing-group-assisted methods have proven to be one of the most efficient and popular solutions to the site-selectivity problem.^7–16 A wide range of directing groups (DGs) have been used for the ortho C(sp)²–H functionalization^7–11 and meta C(sp)²–H functionalization^12–14 of arenes via coordination between the DGs and the transition metal. However, the para C(sp)²–H functionalization^15,16 of arenes is rarely explored and still represents a challenge, especially for arene molecules lacking functional groups.

Transition-metal-catalyzed insertion of a carbene into a C–H bond reaction has proven to be a promising and efficient strategy for undirected C–H functionalization.^17–19 However, highly site-selective C(sp)²–H bond functionalization of unactivated arenes with diazo compounds remains a challenge due to the presence of several competing reactions when mixing an alkyl-substituted benzene with diazo esters under the catalysis of transition metals. For instance, the rhodium-catalyzed benzylic C(sp)³–H functionalization of toluene has been reported by the groups of Thu and Davies.^20,21 Recently, the application of gold catalysts to carbene transfer reactions has attracted considerable interest since gold carbenes display very unique reactivity and selectivity compared to those of other noble metals such as rhodium, copper, and palladium.^22–25 Gold(I)-catalyzed C(sp)²–H bond functionalizations of activated arenes such as phenols, N-acylanilines, and anisoles with α-diazoesters have been reported in recent years.^26–30 More recently, gold(I)-catalyzed highly para-selective C(sp)²–H bond functionalizations of unactivated arenes have also been developed by the groups of Ma and Liu.^31–34 However, the non-recyclability of expensive homogeneous gold catalysts and the decay of cationic gold(I) limit their application in large-scale synthesis or multistep syntheses. Recycling of homogeneous precious metal catalysts is a task of great economic and environmental importance in industry. Anchoring of existing gold complexes on various supports appears to be an attractive strategy for addressing this problem.^35–38 To our knowledge, no example of a heterogeneous gold-catalyzed C(sp)²–H bond functionalization of arenes has been described until now.

Recently, mesoporous silica MCM-41 has been widely used as an ideal support for anchoring homogeneous metal complexes, owing to its excellent properties such as ultrahigh surface area, large and defined pore sizes, high pore volume, and high thermal stability. ³⁹ In recent years, functionalized MCM-41-bound Au(I) or Au(III) complexes have been successfully applied to various organic reactions as highly effective and recyclable catalysts.^40–44 To further expand our Au(I)-MCM-41 chemistry toolbox,^42–44 herein we report the first heterogeneous gold(I)-catalyzed para-selective C(sp)²–H bond alkylation of unactivated arenes with α-aryl-α-diazoesters possessing electron-withdrawing groups as activating groups on the aryl rings (Scheme 1).

Scheme 1.

Heterogeneous gold(I)-catalyzed para-selective C–H bond alkylation of unactivated arenes with diazoesters.

Results and discussion

Several MCM-41-anchored diphenylphosphine gold(I) complexes [MCM-41-PPh₂-AuX] were easily prepared via a simple procedure, as illustrated in Scheme 2. ⁴⁴ First, MCM-41-anchored diphenylphosphine ligand (MCM-41-PPh₂) was prepared by the condensation of commercially available 2-(diphenylphosphino)ethyltriethoxysilane with mesoporous MCM-41 at 100°C in toluene for 24 h, followed by the reaction with Me₃SiCl at room temperature in toluene for 24 h. Next, MCM-41-PPh₂ was reacted with Me₂SAuCl at room temperature in dichloromethane for 8 h, followed by treatment with various silver salts (AgX = AgOTf, AgNTf₂, AgSbF₆, and AgBF₄) at room temperature for 0.5 h to afford the MCM-41-PPh₂-AuX complexes as gray powders.

Scheme 2.

Preparation of the MCM-41-PPh₂-AuX complexes.

In our initial screening experiments, the reaction of toluene (1a) with methyl 2-(2-chlorophenyl)-2-diazoacetate (2a) was investigated to optimize the reaction conditions, and the results are summarized in Table 1. First, the efficiency of various heterogeneous gold(I) catalysts was examined with toluene as the solvent at room temperature, and a significant catalyst effect was observed (entries 1–5). The use of MCM-41-PPh₂-AuCl as the catalyst did not produce the desired product 3a (entry 1). When MCM-41-PPh₂-AuOTf was used as the catalyst, the reaction was complete within 5 min and afforded the desired product 3a in 96% yield (entry 2), while MCM-41-PPh₂-AuNTf₂ and MCM-41-PPh₂-AuSbF₆ were substantially less effective and MCM-41-PPh₂-AuBF₄ was ineffective (entries 3–5). The reaction did not proceed without a gold catalyst (entry 6). When homogeneous Ph₃PAuOTf was employed as the catalyst, the desired product 3a was isolated in 97% yield (entry 7), which indicated that the catalytic activity of MCM-41-PPh₂-AuOTf was comparable with that of Ph₃PAuOTf. It should be noted that this heterogeneous gold(I)-catalyzed reaction proceeded effectively, even when only two equivalents of toluene (1a) were used as the substrate in CH₂Cl₂ as the solvent, providing 3a in 85% yield within 30 min (entry 8). We next examined the effect of the gold catalyst loading on the model reaction. The reaction proceeded smoothly even when the amount of the gold catalyst was reduced to 3 mol%, providing the target product 3a in 93% yield within 20 min (entry 9). Further reducing the amount of the gold catalyst to 1 mol% resulted in a decreased yield and required a relatively longer reaction time (entry 10). To show the practical application of this method, we carried out the reaction under air, to our delight, the desired product 3a could also be isolated in 95% yield (entry 11). Thus, the optimized reaction conditions for this transformation are the use of 5 mol% of MCM-41-PPh₂-AuOTf with toluene as both substrate and solvent at room temperature under argon for 5 min (entry 2).

Table 1.

Optimization of the reaction conditions. ^a

Entry	Au catalyst (mol%)	Time	Isolated yield (%)
1	MCM-41-PPh2-AuCl (5)	24 h	0
2	MCM-41-PPh2-AuOTf (5)	5 min	96
3	MCM-41-PPh2-AuNTf2 (5)	24 h	17
4	MCM-41-PPh2-AuSbF6 (5)	30 min	47
5	MCM-41-PPh2-AuBF4 (5)	24 h	0
6	–	24 h	0
7	Ph3PAuOTf (5)	3 min	97
8 b	MCM-41-PPh2-AuOTf (5)	30 min	85
9	MCM-41-PPh2-AuOTf (3)	20 min	93
10	MCM-41-PPh2-AuOTf (1)	1.5 h	81
11 c	MCM-41-PPh2-AuOTf (5)	5 min	95

a

Reaction conditions: 2a (0.4 mmol), gold catalyst (0.02 mmol), toluene 1a (1.0 mL), room temperature, and Ar.

b

Toluene 1a (0.8 mmol) was used in CH₂Cl₂ (1.0 mL).

c

Reaction was run under air.

The optimized conditions were then used in the reactions of a wide range of unactivated arenes 1 with methyl 2-(2-chlorophenyl)-2-diazoacetate (2a) and the results are summarized in Table 2. The reactions of unactivated arenes bearing various alkyl groups 1a-g with 2a were completed within 5 min at room temperature, providing exclusively the para-C(sp)²–H bond alkylation products 3a-g in 70%–97% yields. Interestingly, benzene (1h) could also undergo the C(sp)²–H bond alkylation with 2a to give the expected product 3h in good yield. Notably, none of the products derived from C(sp)³–H insertion or ortho- or meta-C(sp)²–H bond functionalization were detected. In addition, disubstituted or trisubstituted benzenes 1i-l were compatible with the standard conditions and reacted with 2a to afford the corresponding alkylated products 3i-l in high to excellent yields. We also performed the gram scale reaction of 2a (5.0 mmol) with 1a (5.0 mL) under the standard conditions, providing the desired 3a in 92% yield.

Table 2.

Substrate scope of various unactivated arenes.^a,b

a

Reaction conditions: 2a (0.4 mmol), MCM-41-PPh₂-AuOTf (0.02 mmol), arene 1 (1.0 mL), room temperature, Ar, and 5 min.

b

Isolated yield.

c

The gram scale reaction was carried out with 2a (5.0 mmol), MCM-41-PPh₂-AuOTf (0.25 mmol), and toluene 1a (5.0 mL) at room temperature under Ar for 10 min.

We next investigated the substrate scope of this heterogeneous gold(I)-catalyzed, highly para-selective C(sp)²–H bond alkylation of toluene (1a) by varying the components of the α-aryl α-diazoesters 2. As shown in Table 3, an ethyl on the ester group of 2 had no influence on the yield and selectivity of the reaction, with ethyl 2-(2-chlorophenyl)-2-diazoacetate (2b) affording the desired product 3m in 91% yield. However, when sterically hindered isopropyl 2-(2-chlorophenyl)-2-diazoacetate (2c) was used as the substrate, the target product 3n was obtained in only 75% yield. α-Aryl α-diazoesters 2d-g bearing both strong and weak electron-withdrawing groups at the ortho-position of the phenyl ring reacted with toluene (1a) smoothly to furnish the corresponding products 3o-r in good to excellent yields. α-Aryl α-diazoesters 2h and 2i having a strong electron-withdrawing group at the para-position of the phenyl ring were also suitable for the C(sp)²–H bond functionalization of toluene (1a) and afforded the desired products 3s and 3t, respectively, in good yields. However, methyl 2-(4-bromophenyl)-2-diazoacetate (2j) bearing a weak electron-withdrawing group at the para-position delivered the expected product 3u in only 46% yield, indicating that the electron-withdrawing ability of the substituent on the phenyl ring plays a pivotal role in the reaction. In addition, α-aryl α-diazoesters 2k-m having multiple electron-withdrawing groups on the phenyl ring showed high reactivity in this transformation, thus providing the corresponding products 3v-x in good to excellent yields.

Table 3.

Substrate scope of various α-aryl-α-diazoesters.^a,b

a

Reaction conditions: 2 (0.4 mmol), MCM-41-PPh₂-AuOTf (0.02 mmol), toluene 1a (1.0 mL), room temperature, Ar, and 5 min.

b

Isolated yield.

A plausible mechanism for this heterogeneous gold(I)-catalyzed C(sp)²–H bond functionalization of unactivated arenes is shown in Scheme 3.^27,28 First, the cationic gold MCM-41-PPh₂-AuOTf undergoes ligand exchange with the diazoester 2 to form the diazonium ion intermediate A, which collapses to give the MCM-41-bound gold(I) carbene intermediate B. The electrophilic gold(I) carbene intermediate B reacts with the nucleophilic arene 1 to afford gold zwitterionic intermediate C. Finally, intermediate C undergoes a 1,4-H shift and deauration to produce the desired product 3 and regenerate the MCM-41-PPh₂-AuOTf complex.

Scheme 3.

Proposed catalytic cycle.

For the practical application of a heterogeneous precious metal catalyst, its stability and reusability are important factors to be examined. The MCM-41-PPh₂-AuOTf complex can be easily recovered by simple filtration of the reaction solution. We next examined the recycling of the catalyst in the reaction of toluene (1a) with methyl 2-(2-chlorophenyl)-2-diazoacetate (2a). After completion of the reaction, the reaction mixture was diluted with ethyl acetate and filtered. The catalyst was washed with acetone, air-dried, and could be reused directly without further purification. The recovered MCM-41-PPh₂-AuOTf was used in the next cycle, and almost the same yield of 3a was observed for eight consecutive cycles (96%, 95%, 96%, 94%, 95%, 94%, 93%, and 93%, respectively), which indicated that the MCM-41-PPh₂-AuOTf complex exhibits excellent recyclability in this reaction.

Conclusion

In conclusion, we have developed a novel, efficient, and practical heterogeneous gold(I)-catalyzed C(sp)²–H bond functionalization of benzene derivatives with alkyl α-aryl-α-diazoesters in good to excellent yields with high chemo- and site-selectivities. In this method, the electron-withdrawing groups on the phenyl moiety of the diazoesters effectively promoted the chemo- and site-selective C(sp)²–H bond functionalization. Importantly, this heterogeneous gold(I) catalyst can be easily recovered by simple filtration of the reaction solution and recycled at least seven times with almost consistent activity, thus making this protocol economically and environmentally more acceptable.

Experimental

All reagents were used as received without further purification. The MCM-41-PPh₂-AuOTf, MCM-41-PPh₂-AuNTf₂, MCM-41-PPh₂-AuSbF₆, and MCM-41-PPh₂-AuBF₄ complexes were prepared according to our previous procedure. ⁴⁴ The gold contents were determined to be 0.37, 0.35, 0.36, and 0.38 mmol g⁻¹, respectively, based on inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis (Atomscan 16; TJA Corporation). All the α-aryl-α-diazoesters were prepared according to the literature method. ³² Dichloromethane was dried over P₂O₅ and distilled before use. All reactions were carried out under Ar in oven-dried glassware with magnetic stirring. ¹H NMR spectra were recorded on a Bruker Avance 400 (400 MHz) spectrometer with tetramethylsilane (TMS) as an internal standard using CDCl₃ as the solvent. ¹³C NMR spectra were recorded on a Bruker Avance 400 (100 MHz) spectrometer using CDCl₃ as the solvent. We have identified all the products by comparing their spectroscopic and physical data with that available for the products in the Supplementary Information provided by Ma et al. ³²

Heterogeneous gold(I)-catalyzed C(sp²)–H bond alkylation of benzene derivatives with α-aryl-α-diazoesters: general procedure

A 10 mL Schlenk tube was charged with MCM-41-PPh₂-AuOTf (54 mg, 5 mol%) and arene 1 (0.2 mL) at room temperature under Ar. Next, a solution of α-aryl-α-diazo- ester 2 (0.4 mmol) dissolved in arene 1 (0.8 mL) was introduced into the reaction mixture by a syringe over 1 min. The resulting mixture was continually stirred at room temperature for 5 min. The mixture was diluted with EtOAc (10 mL) and filtered. The gold catalyst was washed with acetone (2 × 3 mL), air-dried, and reused in the next run. The filtrate was concentrated under reduced pressure, and the residue was purified by flash column chromatography on silica gel (PE/EtOAc = 30:1) to provide the desired product 3.

Methyl 2-(2-chlorophenyl)-2-p-tolylacetate (3a): ³² White solid; m.p. 60–61°C. ¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.33 (m, 1H), 7.25–7.11 (m, 7H), 5.44 (s, 1H), 3.71 (s, 3H), 2.31 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.5, 137.2, 136.8, 134.2, 134.0, 130.0, 129.5, 129.4, 128.8, 128.5, 126.9, 53.4, 52.4, and 21.0.

Methyl 2-(2-chlorophenyl)-2-(4-ethylphenyl)acetate (3b): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.38–7.35 (m, 1H), 7.25–7.14 (m, 7H), 5.45 (s, 1H), 3.73 (s, 3H), 2.63 (q, J = 7.6 Hz, 2H), 1.22 (t, J = 7.6 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.5, 143.5, 136.8, 134.2, 134.1, 130.1, 129.5, 128.8, 128.5, 128.3, 126.9, 53.4, 52.4, 28.5, and 15.3.

Methyl 2-(2-chlorophenyl)-2-(4-propylphenyl)acetate (3c): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.39–7.36 (m, 1H), 7.24–7.13 (m, 7H), 5.45 (s, 1H), 3.75 (s, 3H), 2.57 (t, J = 7.8 Hz, 2H), 1.66–1.60 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.6, 142.0, 136.8, 134.3, 130.1, 129.5, 128.8, 128.7, 128.5, 126.9, 53.4, 52.4, 37.7, 24.4, and 13.9.

Methyl 2-(2-chlorophenyl)-2-(4-isopropylphenyl)acetate (3d): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.32–7.29 (m, 1H), 7.22–7.11 (m, 7H), 5.38 (s, 1H), 3.67 (s, 3H), 2.84–2.78 (m, 1H), 1.17 (d, J = 7.2 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃): δ = 171.6, 147.1, 135.8, 133.3, 133.2, 129.1, 128.5, 127.8, 127.5, 125.9, 125.8, 52.3, 51.4, 32.7, and 22.9.

Methyl 2-(4-tert-butylphenyl)-2-(2-chlorophenyl)acetate (3e): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.32–7.27 (m, 3H), 7.23–7.12 (m, 5H), 5.39 (s, 1H), 3.67 (s, 3H), 1.23 (s, 9H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.6, 150.4, 136.8, 134.2, 133.9, 130.1, 129.5, 128.5, 126.9, 125.7, 53.3, 52.4, 34.5, and 31.3.

Methyl 2-(2-chlorophenyl)-2-(4-isobutylphenyl)acetate (3f): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.38 (dd, J = 5.4, 3.8 Hz, 1H), 7.25–7.17 (m, 5H), 7.12 (d, J = 8.4 Hz, 2H), 5.45 (s, 1H), 3.74 (s, 3H), 2.46 (d, J = 7.2 Hz, 2H), 1.89–1.81 (m, 1H), 0.90 (d, J = 6.8 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.6, 141.0, 136.9, 134.3, 134.2, 130.1, 129.6, 129.5, 128.6, 128.5, 126.9, 53.4, 52.4, 45.1, 30.1, and 22.4.

Methyl 2-(biphenyl-4-yl)-2-(2-chlorophenyl)acetate (3g): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.57 (d, J = 8.0 Hz, 4H), 7.45–7.26 (m, 7H), 7.24–7.20 (m, 2H), 5.53 (s, 1H), 3.78 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.4, 140.6, 140.5, 136.5, 136.1, 134.3, 130.1, 129.7, 129.3, 128.8, 128.7, 127.5, 127.4, 127.1, 127.0, 53.4, and 52.6.

Methyl 2-(2-chlorophenyl)-2-phenylacetate (3h): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.32–7.28 (m, 3H), 7.27–7.21 (m, 3H), 7.16–7.11 (m, 3H), 5.42 (s, 1H), 3.67 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.3, 137.1, 136.5, 134.2, 130.1, 129.6, 128.9, 128.7, 128.6, 127.6, 126.9, 53.8, and 52.5.

Methyl 2-(2-chlorophenyl)-2-(2,4-dimethylphenyl)acetate (3i): ³² White solid; m.p. 67–68°C. ¹H NMR (400 MHz, CDCl₃): δ = 7.40–7.37 (m, 1H), 7.23–7.14 (m, 2H), 7.03–6.98 (m, 4H), 5.54 (s, 1H), 3.75 (s, 3H), 2.31 (s, 3H), 2.17 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.8, 137.4, 136.6, 136.1, 134.5, 132.6, 131.7, 130.2, 129.5, 128.6, 128.0, 127.0, 126.9, 52.5, 50.8, 21.0, and 19.5.

Methyl 2-(2-chlorophenyl)-2-(3,4-dimethylphenyl)acetate (3j): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.38–7.35 (m, 1H), 7.24–7.17 (m, 3H), 7.11 (d, J = 7.6 Hz, 1H), 7.05–7.01 (m, 2H), 5.41 (s, 1H), 3.74 (s, 3H), 2.24 (s, 6H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.6, 137.1, 136.8, 136.0, 134.4, 134.2, 130.1, 130.0, 129.5, 128.5, 126.9, 126.2, 53.4, 52.4, 19.8, and 19.4.

Methyl 2-(2-chlorophenyl)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetate (3k): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.38–7.35 (m, 1H), 7.25–7.17 (m, 3H), 7.05–6.97 (m, 3H), 5.40 (s, 1H), 3.74 (s, 3H), 2.76–2.72 (m, 4H), 1.81–1.74 (m, 4H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.6, 137.6, 136.8, 136.6, 134.2, 133.9, 130.1, 129.5, 129.4, 128.5, 126.9, 125.9, 53.5, 52.5, 29.4, 29.1, 23.1, and 23.0.

Methyl 2-(2-chlorophenyl)-2-mesitylacetate (3l): ³² White solid; m.p. 109–110°C. ¹H NMR (400 MHz, CDCl₃): δ = 7.43 (dd, J = 7.6, 1.2 Hz, 1H), 7.22–7.18 (m, 1H), 7.11–7.08 (m, 1H), 6.91 (s, 2H), 6.82 (dd, J = 7.6, 1.6 Hz, 1H), 5.60 (s, 1H), 3.73 (s, 3H), 2.29 (s, 3H), 2.18 (s, 6H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.7, 137.3, 137.1, 135.6, 134.6, 131.8, 130.0, 129.6, 129.5, 128.5, 126.8, 52.4, 49.7, 20.9, and 20.7.

Ethyl 2-(2-chlorophenyl)-2-p-tolylacetate (3m): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.38–7.35 (m, 1H), 7.24–7.12 (m, 7H), 5.41 (s, 1H), 4.25–4.17 (m, 2H), 2.33 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.1, 137.2, 137.0, 134.3, 134.2, 130.1, 129.6, 129.5, 128.8, 128.5, 126.9, 61.4, 53.6, 21.1, and 14.2.

Isopropyl 2-(2-chlorophenyl)-2-p-tolylacetate (3n): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.29–7.26 (m, 1H), 7.15–7.03 (m, 7H), 5.29 (s, 1H), 5.02–4.97 (m, 1H), 2.24 (s, 3H), 1.15 (d, J = 6.0 Hz, 3H), 1.11 (d, J = 6.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 171.5, 137.2, 137.1, 134.3, 134.2, 130.1, 129.5, 129.4, 128.8, 128.4, 126.8, 68.7, 53.8, 21.7, 21.6, and 21.1.

Methyl 2-(2-fluorophenyl)-2-p-tolylacetate (3o): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.18–7.11 (m, 4H), 7.07 (d, J = 8.4 Hz, 2H), 7.01–6.93 (m, 2H), 5.18 (s, 1H), 3.66 (s, 3H), 2.25 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.5, 160.5 (d, J = 245.0 Hz), 137.3, 134.1, 129.9 (d, J = 3.4 Hz), 129.5, 128.9 (d, J = 8.3 Hz), 128.7, 126.4 (d, J = 14.4 Hz), 124.1 (d, J = 3.6 Hz), 115.3 (d, J = 22.0 Hz), 52.4, 49.5 (d, J = 3.2 Hz), and 21.1.

Methyl 2-(2-bromophenyl)-2-p-tolylacetate (3p): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.45 (d, J = 8.0 Hz, 1H), 7.16–6.95 (m, 7H), 5.36 (s, 1H), 3.62 (s, 3H), 2.22 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.6, 138.5, 137.3, 134.3, 133.0, 130.3, 129.6, 128.8, 127.6, 125.1, 56.0, 52.5, and 21.2.

Methyl 2-(2-iodophenyl)-2-p-tolylacetate (3q): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.87–7.84 (m, 1H), 7.29–7.24 (m, 2H), 7.19–7.12 (m, 4H), 6.95–6.91 (m, 1H), 5.36 (s, 1H), 3.74 (s, 3H), and 2.32 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.6, 141,6, 139.8, 137.2, 134.6, 129.8, 129.5, 129.0, 128.8, 128.5, 101.7, 60.7, 52.5, and 21.2.

Methyl 2-p-tolyl-2-[2-(trifluoromethyl)phenyl]acetate (3r): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.57 (d, J = 7.6 Hz, 1H), 7.40–7.37 (m, 2H), 7.27–7.22 (m, 1H), 7.05 (s, 4H), 5.41 (s, 1H), 3.64 (s, 3H), 2.23 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.5, 137.2, 135.1, 131.9, 131.6, 129.5, 128.6 (q, J = 31.6 Hz), 128.4, 127.3, 125.8 (q, J = 5.8 Hz), 124.5 (q, J = 272.6 Hz), 52.5, 51.8, and 21.0.

Methyl 2-p-tolyl-2-(4-(trifluoromethyl)phenyl)acetate (3s): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.56 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 5.04 (s, 1H), 3.75 (s, 3H), 2.33 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 171.4, 141.8, 136.4, 133.8, 128.6, 128.5 (q, J = 32.4 Hz), 128.0, 127.3, 124.5 (q, J = 3.7 Hz), 123.1 (q, J = 270.4 Hz), 55.4, 51.5, and 20.0.

Methyl 2-(4-nitrophenyl)-2-p-tolylacetate (3t): ³² Yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.17–8.13 (m, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.20–7.14 (m, 4H), 5.07 (s, 1H), 3.76 (s, 3H), 2.34 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 171.8, 147.2, 146.0, 137.7, 134.2, 129.6, 129.5, 128.4, 123.6, 56.3, 52.6, and 21.1.

Methyl 2-(4-bromophenyl)-2-p-tolylacetate (3u): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.34 (d, J = 8.4 Hz, 2H), 7.13–7.01 (m, 6H), 4.85 (s, 1H), 3.64 (s, 3H), 2.22 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.7, 137.8, 137.3, 135.1, 131.6, 130.3, 129.5, 128.2, 121.3, 55.9, 52.4, and 21.0.

Methyl 2-(2-bromo-4-fluorophenyl)-2-p-tolylacetate (3v): ³² Colorless oil.¹H NMR (400 MHz, CDCl₃): δ = 7.24–7.20 (m, 1H), 7.15–7.10 (m, 1H), 7.06 (s, 4H), 6.89–6.85 (m, 1H), 5.31 (s, 1H), 3.65 (s, 3H), 2.24 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.4, 161.4 (d, J = 249.4 Hz), 137.5, 134.5 (d, J = 3.5 Hz), 134.2, 131.3 (d, J = 8.3 Hz), 129.6, 128.6, 124.8 (d, J = 9.4 Hz), 120.1 (d, J = 24.4 Hz), 114.7 (d, J = 20.7 Hz), 55.2, 52.5, and 21.1.

Methyl 2-(2,4-dichlorophenyl)-2-p-tolylacetate (3w): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.31 (s, 1H), 7.10–7.02 (m, 6H), 5.29 (s, 1H), 3.65 (s, 3H), 2.25 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.2, 137.6, 135.5, 134.8, 133.8, 133.7, 131.0, 129.6, 129.3, 128.7, 127.2, 52.9, 52.6, and 21.1.

Methyl 2-(2,3-dichlorophenyl)-2-p-tolylacetate (3x): ³² Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.28 (dd, J = 6.8, 2.8 Hz, 1H), 7.08 (s, 4H), 7.04–6.98 (m, 2H), 5.37 (s, 1H), 3.66 (s, 3H), 2.25 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 172.2, 139.2, 137.6, 133.6, 133.3, 132.6, 129.6, 129.4, 128.8, 128.3, 127.2, 54.3, 52.6, and 21.1.