Palladium-Catalyzed Decarboxylative ortho ... - ACS Publications

Nov 10, 2017 - (2C), 128.4 (2C), 127.4, 39.2, 34.9, 21.4; HRMS (FTMS-ESI) calcd for C17H18NO2 [M + H]+ 268.1332, found 268.1331. 2-Benzoyl-4-fluoro-N,...
1 downloads 12 Views 2MB Size
Download PDF
Article pubs.acs.org/joc

Palladium-Catalyzed Decarboxylative ortho-Acylation of Benzamides with α‑Oxocarboxylic Acids Kun Jing,† Jia-Ping Yao,† Zhong-Yuan Li,† Qi-Li Li,† Hao-Sheng Lin,† and Guan-Wu Wang*,†,‡ †

CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Hefei National Laboratory for Physical Sciences at Microscale, and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China ‡ State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, P. R. China S Supporting Information *

ABSTRACT: A palladium-catalyzed decarboxylative ortho-acylation of tertiary benzamides with α-oxocarboxylic acids by weak O-coordination has been described. This reaction proceeds smoothly with a high monoacylation selectivity, affording orthoacylated benzamides in moderate to good yields. When secondary benzamides are employed as the substrates, the formed orthoacylated benzamides undergo further intramolecular cyclization to provide isoindolinone derivatives. In addition, several transformations of the synthesized ortho-acylated benzamides into a diversity of synthetically valuable products have been demonstrated.

■

oxime,6 azo,7 acetamide,8 indole,9 and others10 have been utilized in the C−H acylation with α-oxocarboxylic acids. Although significant achievements in this field have been accomplished so far, many challenges still remain and further developments are demanded. For example, a majority of the previous studies heavily relied on the usage of N-coordinating groups including pyridine, oxime, and azo; meanwhile, the weak O-coordinating groups such as tertiary benzamides were rarely investigated in the decarboxylative acylation. Tertiary benzamides appear in a large number of pharmaceuticals, natural products, and functional materials as key structural motifs and crucial intermediates.11 However, the transition-metal-catalyzed direct ortho-C−H functionalization of tertiary amides is relatively difficult due to the weak O-coordination of the tertiary amide group and the electron-deficiency of the aryl ring.12 In 2011, the Kim group first presented the rhodiumcatalyzed oxidative acylation of tertiary benzamides with aryl aldehydes as the acylation source.13 Nevertheless, the palladium-catalyzed decarboxylative acylation of tertiary benzamides has not been reported yet. With our continuing interest in developing more C−H bond activation protocols,14 herein we disclose the first example for the palladium-catalyzed decarboxylative acylation of tertiary benzamides with αoxocarboxylic acids by weak O-coodination.15 It is intriguing to find that when secondary benzamides are employed as the

INTRODUCTION Aromatic ketones are crucial structural motifs and precursors for the synthesis of a wide range of natural products, biologically active compounds, and functional materials.1 Traditional methods such as Friedel−Crafts acylation reaction have already been regarded as the most frequently used synthetic strategies to access aromatic ketones. However, the application of this unquestionably effective Friedel−Crafts reaction is somehow limited in organic synthesis, due to its requirements of a stoichiometric amount of Lewis acid, bad functional group tolerance, and poor regioselectivity.2 Consequently, it is highly desirable to develop more efficient methodologies for the synthesis of aromatic ketones to overcome the above-mentioned disadvantages. Over the past decades, the transition-metal-catalyzed decarboxylative cross-coupling reactions have emerged as increasingly valid tools for the construction of diaryl ketones due to their atom-economic and environment-friendly advantages by avoiding the preparation of prefunctionalized starting materials and the usage of stoichiometric organometallic reagents.3 In 2008, Gooßen et al. initially reported the Pdcatalyzed decarboxylative acylation of aryl bromides with αoxocarboxylic carboxylate salts to provide unsymmetric diaryl ketones.4 Subsequently, Ge and co-workers elegantly disclosed the Pd-catalyzed functional group-directed decarboxylative ortho-acylation of acetanilides and phenylpyridines by employing α-oxocarboxylic acids as the acylation source.5 After these pioneering works, a vast number of directing groups such as © 2017 American Chemical Society

Received: October 8, 2017 Published: November 10, 2017 12715

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry Table 1. Optimization of the Reaction Conditionsa

a b

entry

catalyst

oxidant

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19c 20c,d 21c,f 22c,g

Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(TFA)2 PdCl2 Pd(CH3CN)2Cl2 Pd(PhCN)2Cl2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2

K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 Na2S2O8 (NH4)2S2O8 Oxone Ag2O K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8 K2S2O8

additive

D-CSA

TsOH CH3SO3H TFA AcOH TfOH TfOH TfOH TfOH TfOH TfOH TfOH TfOH TfOH TfOH TfOH TfOH TfOH

solvent

yield (%)b

DCE 1,4-dioxane CH3CN diglyme DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE

40 25 trace trace 58 47 60 trace 43 66 64 57 49 trace 63 44 50 52 71 77 (77e) 73 62

Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), Pd(OAc)2 (0.01 mmol), K2S2O8 (0.2 mmol), additive (0.05 mmol), DCE (1 mL), 80 °C, 24 h. Isolated yields based on 1a. cAdditive (0.02 mmol). d70 °C. e0.2 mmol scale. f60 °C. g90 °C.

substrates, the formed ortho-acylated benzamides can undergo further intramolecular cyclization to provide isoindolinone derivatives. In addition, further transformations of the synthesized ortho-acylated benzamides have been demonstrated.

entry 11 vs entry 10). Other oxidants such as (NH4)2S2O8, Oxone, and Ag2O were also explored, yet they gave worse results than K2S2O8 (Table 1, entries 12−14 vs entry 10). The yield of 3aa was reduced when other palladium catalysts including Pd(TFA) 2, PdCl2 , Pd(CH 3CN) 2Cl2, and Pd(PhCN)2Cl2 were further examined (Table 1, entries 15−18 vs entry 10). Gratifyingly, product 3aa was isolated in 71% yield when the amount of TfOH was reduced to 0.2 equiv (Table 1, entry 19). Decreasing the temperature to 70 °C provided 3aa in a better yield of 77% (Table 1, entry 20). Further decreasing the temperature to 60 °C or increasing the temperature to 90 °C lowered the yield of 3aa slightly (Table 1, entries 21 and 22). Therefore, the optimized conditions of the Pd-catalyzed decarboxylative ortho-acylation of the tertiary benzamides were as follows: 10 mol % Pd(OAc)2 as the catalyst, 2.0 equiv of K2S2O8 as the oxidant, 20 mol % TfOH as the additive, and 2.0 equiv of 2a as the partner of 1a. The reaction performed best at 70 °C for 24 h with DCE as the solvent. With the optimized reaction conditions in hand, the substrate scope of tertiary benzamides 1 was explored by reacting with 2a. As shown in Table 2, the reactions proceeded smoothly to afford ortho-acylation products 3aa−3pa in moderate to good yields. Benzamides 1b and 1c with para-substituted electrondonating groups (OMe and Me) gave the corresponding products 3ba and 3ca in 70% and 74% yields, respectively. Halogen-substituted benzamides 1d−1f were compatible with our optimal reaction conditions. In particular, the chlorosubstituted benzamide 1e gave the corresponding product 3ea

■

RESULTS AND DISCUSSION In our initial investigation, we chose N,N-dimethylbenzamide (1a) and phenylglyoxylic acid (2a) as the model substrates to screen the reaction conditions, and selected results are summarized in Table 1. Product 3aa was obtained in 40% yield when using 10 mol % Pd(OAc)2 as the catalyst, 2.0 equiv of K2S2O8 as the oxidant, and 1,2-dichloroethane (DCE) as the solvent at 80 °C for 24 h (Table 1, entry 1). Other solvents including 1,4-dioxane, CH3CN, and diglyme were screened, but no better results were achieved (Table 1, entries 2−4). To our delight, when 0.5 equiv of an acid was added to this reaction as the additive, the yield of 3aa was affected dramatically. Particularly, trifluoromethanesulfonic acid (TfOH) performed best for this catalytic reaction among all examined acids including D-camphorsulfonic acid (D-CSA), p-toluenesulfonic acid (TsOH), methanesulfonic acid (CH3SO3H), trifluoacetic acid (TFA), and acetic acid (AcOH), providing 3aa in 66% yield (Table 1, entries 5−10). The triflate anion is generally believed to tune the electrophilicity of the Pd(II) center and promote the insertion of Pd(II) into the aromatic C−H bonds of tertiary benzamides.16 Product 3aa was obtained in a slightly lower yield when K2S2O8 was replaced with Na2S2O8 (Table 1, 12716

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry Table 2. Pd-Catalyzed Decarboxylative Acylation of Tertiary Benzamides 1a−1p with Phenylglyoxylic Acid (2a)a,b

a

Reaction conditions: 1a (1b−1p, 0.2 mmol), 2a (0.4 mmol), Pd(OAc)2 (0.02 mmol), K2S2O8 (0.4 mmol), TfOH (0.04 mmol), DCE (2 mL), 70 °C, 24 h. bIsolated yields based on 1.

in 79% yield. It is worthy to mention that the bromo atom in 1f remained intact during the reaction and provided 3fa in a good yield of 72%, and it may offer further transformations via transition-metal-catalyzed cross-coupling reactions.17 To our delight, meta-substituted electron-rich or electron-deficient benzamides exhibited good regioselectivity, and the orthoacylation mainly occurred at the less hindered position, providing corresponding products 3ga and 3ha in 66% and 58% yields, respectively. Furthermore, the reaction could be applied to other N,N-disubstituted benzamides. The N,N-

diethylbenzamide (1i) afforded product 3ia in 72% yield, and the para-substituted or meta-substituted N,N-diethylbenzamides gave 3ja, 3ka, and 3la in 60%, 73%, and 63% yields, respectively. Satisfactorily, benzamide 1m bearing the pyrrolidino moiety proceeded efficiently to give 3ma in 70% yield. When other cyclic benzamides such as 1n and 1o were used, the desired products 3na and 3oa were obtained in relatively lower yields of 37% and 47%, respectively. Intriguingly, the benzamides with different substituents attached to the nitrogen atom could also work well in this catalytic system. For example, 12717

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry when N-ethyl-N-methylbenzamide (1p) was employed, product 3pa was isolated in 70% yield. It should be noted that benzamides with strong electron-deficient groups such as NO2, CN, and CO2Me at the para-position gave disappointing results even with higher temperatures or more additives. To further explore the substrate scope and limitation, a vast variety of α-oxocarboxylic acids 2b−2r were employed to react with 1a under the optimal reaction conditions, and the results are shown in Table 3. Phenylglyoxylic acids bearing electronrich or electron-deficient groups at the para-position proved to be suitable substrates for this transformation, affording the corresponding products 3ab−3ag in 50−70% yields. Similarly, meta-substituted phenylglyoxylic acids worked well to give the

desired products 3ah−3al in 62−75% yields. The reaction could also be extended to ortho-substituted phenylglyoxylic acids to produce 3am, 3an, and 3ao in 56%, 60%, and 70% yields, respectively. The disubstituted phenylglyoxylic acids also proved to be feasible for this procedure and provided products 3ap and 3aq in 58% and 72% yields, respectively. Finally, when 2-(naphthalene-1-yl)-2-oxoacetic acid (2r) was employed as the acyl source, the corresponding product 3ar was obtained in 70% yield. In an attempt to extend the substrates from aromatic oxocarboxylic acids to aliphatic oxocarboxylic acids, the reaction of 1a with pyruvic acid (2s) under our optimized conditions failed to give the desired product. Great efforts were then made to seek out the best conditions for the aliphatic acylation of tertiary benzamides. To our delight, when K2S2O8 was replaced with Na2S2O8 and when AgOAc was added, 1a could react with 2s to afford the desired product 3as in 44% yield. Similarly, other representative tertiary benzamides such as N,Ndiethylbenzamide (1i) and cyclic benzamide 1m were also reactive under the optimized conditions, providing acetylated products 3is and 3ms in 47% and 35% yields, respectively (Table 4).

Table 3. Pd-Catalyzed Decarboxylative Acylation of N,NDimethylbenzamide (1a) with α-Oxocarboxylic Acids 2b− 2ra,b

Table 4. Pd-Catalyzed Decarboxylative Acylation of Tertiary Benzamides with Pyruvic Acid (2s)a,b

a

Reaction conditions: 1a (1i or 1m, 0.5 mmol), 2s (1.0 mmol), Pd(OAc)2 (0.05 mmol), Na2S2O8 (1.0 mmol), AgOAc (0.25 mmol), TfOH (0.1 mmol), DCE (2.5 mL), 100 °C, 48 h. bIsolated yields based on 1.

It is noteworthy that we did not obtain the bis-acylated products from the above acylation reactions, indicating the highly selective monoacylation of the present methodology. We could not detect any bis-acylated products by analyzing the 1H NMR and mass spectra of the crude reaction mixtures either. Furthermore, we attempted the second acylation by using the monoacylated products as the starting materials under the standard conditions, but failed to isolate any bis-acylated products either. The reasons may arise from the following two aspects. First, the monoacylated products possess an increased large steric hindrance at the ortho-position of the amide group on the phenyl ring, which may prevent further ortho-palladation to form bis-acylated products. Second, the electron-withdrawing nature of the introduced acyl group would decrease the electron density of the phenyl ring of benzamides and is unfavorable for the further acylation reaction. Intriguingly, when different secondary benzamides (4a−4d) were employed as the substrates, their reactions with

a

Reaction conditions: 1a (0.2 mmol), 2b (2c−2r, 0.4 mmol), Pd(OAc)2 (0.02 mmol), K2S2O8 (0.4 mmol), TfOH (0.04 mmol), DCE (2 mL), 70 °C, 24 h. bIsolated yields based on 1a. 12718

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry Table 5. Pd-Catalyzed Decarboxylative Acylation of Secondary Benzamides 4a−4d with α-Oxocarboxylic Acids 2a,b

a

Reaction conditions: 4a (4b−4d, 0.2 mmol), 2a (2c or 2f, 0.4 mmol), Pd(OAc)2 (0.02 mmol), K2S2O8 (0.4 mmol), TfOH (0.04 mmol), DCE (2 mL), 70 °C, 24 h. bIsolated yields based on 4. cTfOH was replaced by TsOH.

oxazin-1-one (8aa)20 were successfully synthesized from 3aa in 91% and 70% yields by reacting with hydrazine and hydroxylamine, respectively. In addition, 3aa could react with NH4OAc and EtOH in a sealed tube to give isoindolin 9aa in 86% yield. Compounds 3, 5, and 6aa−9aa were characterized by HRMS, 1H NMR, 13C NMR, and 19F NMR spectroscopies and were assigned as the ortho-functionalized products. All mass spectra of these products gave the correct molecular ion peaks. Their 1H NMR and 13C NMR spectra displayed the expected chemical shifts as well as the splitting patterns for all protons and carbons. Particularly, products 3aa, 3ia, 3ma, 3oa, and 6aa−8aa are known compounds, and their 1H NMR spectra were consistent with those reported in the literature.13,18−20 For products 3ga, 3ha, and 3la, the regioselectivity could be confirmed by the diagnostic singlet at 7.20−7.41 ppm in their 1 H NMR spectra, indicating that the ortho-acylation occurred at the less hindered position. To gain insight into the reaction mechanism, additional experiments had been performed (Scheme 2). First, when radical scavenger 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO) was added to the reaction system of 1a and 2a, only a trace amount of 3aa was detected, while the acyl radical− TEMPO adduct 10 was isolated in 31% yield, indicating that the reaction probably involved a free radical process. Second, the intermolecular kinetic isotope effect (KIE) experiment was studied, and it was found that the kH/kD for the reaction of 1a/ [D5]-1a with 2a was 2.5, hinting that the C−H cleavage might be involved in our catalytic system as the rate-determining step. Finally, intermolecular competition experiments between differently substituted benzamides and phenylglyoxylic acids were investigated. The product distribution (43% for 3ba vs 18% for 3ea) for the reactions of 4-methoxy-N,N-dimethylbenzamide (1b) and 4-chloro-N,N-dimethylbenzamide (1e)

representative 2a under our optimized conditions for tertiary benzamides afforded isoindolinone detivatives 5aa−5da, which should be generated through the intramolecular cyclization of the formed ortho-acylated precursors. If TfOH was replaced by TsOH, the product yields of 5aa−5da could be significantly improved from 43−52% to 76−82%. Likewise, other representative phenylglyoxylic acids 2c and 2f also worked well with 4b to give the desired products 5bc and 5bf in 75% and 60% yields, respectively, when TsOH was used as the additive (Table 5). In order to demonstrate the synthetic utility of synthesized ortho-acylated benzamides, we conducted further transformations of the representative 3aa to provide several synthetically valuable products (Scheme 1). For example, 3aa could be reduced by NaBH4 to provide the lactone 3-phenylisobenzofuran-1(3H)-one (6aa)18 in 86% yield. Furthermore, 4-phenylphthalazin-1(2H)-one (7aa)19 and 4-phenyl-1H-benzo[d][1,2]Scheme 1. Transformations of 2-Benzoyl-N,Ndimethybenzamide (3aa)

12719

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry Scheme 2. Preliminary Mechanistic Studies

with 2a indicated that the electron-rich benzamides were inherently more reactive. In contrast, the reactions of 1a with 4methoxyphenylglyoxylic acid (2b) and 4-trifluoromethylphenylglyoxylic acid (2g) gave the corresponding products 3ab and 3ag in 26% and 34%, respectively, displaying that the substituents on phenylglyoxylic acids had little influence on the reactivity. On the basis of the above experimental results and the previous literature, a plausible reaction mechanism is proposed (Scheme 3). At first, this transformation is believed to start with the formation of a five-membered palladacycle I by the orthopalladation of 1 with a Pd(II) species. Then, I undergoes oxidative coupling with the acyl radical II, which is produced by decarboxylation of 2 in the presence of K2S2O8 to furnish the Pd(III) or Pd(IV) intermediate III.21 Finally, the acylated product 3 is generated by reductive elimination with the simultaneous release of a Pd(II) species to complete the catalytic cycle.

Scheme 3. Plausible Reaction Mechanism

■

CONCLUSIONS In summary, a novel Pd-catalyzed decarboxylative orthoacylation of tertiary benzamides with α-oxocarboxylic acids 12720

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry via sp2 C−H bond activation has been developed. This protocol can be applied to a wide range of tertiary benzamides and αoxocarboxylic acids with both electron-donating and electronwithdrawing groups in moderate to good yields. It is intriguing to find that when the tertiary benzamides are replaced with secondary benzamides, the formed ortho-acylated benzamides undergo further intramolecular cyclization to provide isoindolinone derivatives. In addition, the synthesized orthoacylated benzamides can be transformed to various biologically active compounds and synthetically valuable products.

■

(d, JC−F = 251.0 Hz), 139.4 (d, JC−F = 6.4 Hz), 136.4, 133.9 (d, JC−F = 3.7 Hz), 133.5, 130.0 (2C), 129.3 (d, JC−F = 8.0 Hz), 128.5 (2C), 118.0 (d, JC−F = 21.6 Hz), 116.9 (d, JC−F = 23.1 Hz), 39.1, 34.9; HRMS (FTMS-ESI) calcd for C16H15FNO2 [M + H]+ 272.1081, found 272.1085. 2-Benzoyl-4-chloro-N,N-dimethylbenzamide (3ea). By following the general procedure, the reaction of 1e (36.7 mg, 0.2 mmol) with 2a (60.5 mg, 0.4 mmol) gave 3ea (42.4 mg, 79% yield): light yellow solid, mp 84−86 °C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.4 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.56−7.51 (m, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.37 (d, J = 8.0 Hz, 1H), 2.91 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 195.4, 169.6, 138.8, 136.5, 136.3, 134.6, 133.6, 131.1, 130.2 (2C), 129.8, 128.8, 128.6 (2C), 39.2, 34.9; HRMS (FTMS-ESI) calcd for C16H15ClNO2 [M + H]+ 288.0786, found 288.0788. 2-Benzoyl-4-bromo-N,N-dimethylbenzamide (3fa). By following the general procedure, the reaction of 1f (45.6 mg, 0.2 mmol) with 2a (60.3 mg, 0.4 mmol) gave 3fa (47.7 mg, 72% yield): yellow solid, mp 98−99 °C; 1H NMR (400 MHz, CDCl3) δ 7.81−7.76 (m, 2H), 7.69 (dd, J = 8.0, 1.9 Hz, 1H), 7.67 (d, J = 1.9 Hz, 1H), 7.63−7.57 (m, 1H), 7.47 (t, J = 7.7 Hz, 2H), 7.30 (d, J = 8.0 Hz, 1H), 2.91 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 195.3, 169.7, 139.0, 136.8, 136.5, 134.1, 133.6, 132.6, 130.2 (2C), 128.9, 128.6 (2C), 122.6, 39.2, 34.9; HRMS (FTMS-ESI) calcd for C16H15BrNO2 [M + H]+ 332.0281, found 332.0279. 2-Benzoyl-N,N,5-trimethylbenzamide (3ga). By following the general procedure, the reaction of 1g (32.6 mg, 0.2 mmol) with 2a (60.3 mg, 0.4 mmol) gave 3ga (35.2 mg, 66% yield): light yellow solid, mp 78−80 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.3 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.48−7.41 (m, 3H), 7.27−7.21 (m, 2H), 2.94 (s, 3H), 2.88 (s, 3H), 2.43 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 196.6, 171.0, 142.4, 138.4, 137.5, 133.7, 132.9, 130.6, 130.1 (2C), 129.0, 128.4 (2C), 128.1, 39.1, 34.9, 21.6; HRMS (FTMS-ESI) calcd for C17H18NO2 [M + H]+ 268.1332, found 268.1330. 2-Benzoyl-5-chloro-N,N-dimethylbenzamide (3ha). By following the general procedure, the reaction of 1h (36.7 mg, 0.2 mmol) with 2a (60.2 mg, 0.4 mmol) gave 3ha (33.6 mg, 58% yield): light yellow oil; 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.3 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.52−7.40 (m, 5H), 2.95 (s, 3H), 2.92 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 195.7, 169.2, 140.0, 137.7, 136.9, 135.1, 133.4, 131.5, 130.2 (2C), 128.6, 128.5 (2C), 127.6, 39.1, 34.9; HRMS (FTMS-ESI) calcd for C16H15ClNO2 [M + H]+ 288.0786, found 288.0784. 2-Benzoyl-N,N-diethylbenzamide (3ia).13 By following the general procedure, the reaction of 1i (53.7 mg, 0.3 mmol) with 2a (90.1 mg, 0.6 mmol) gave 3ia (60.5 mg, 72% yield): yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.1 Hz, 2H), 7.59−7.49 (m, 3H), 7.47− 7.38 (m, 4H), 3.43 (q, J = 7.1 Hz, 2H), 3.26 (q, J = 7.1 Hz, 2H), 1.12 (t, J = 7.1 Hz, 3H), 1.07 (t, J = 7.1 Hz, 3H). 2-Benzoyl-N,N-diethyl-4-methylbenzamide (3ja). By following the general procedure, the reaction of 1j (38.3 mg, 0.2 mmol) with 2a (60.0 mg, 0.4 mmol) gave 3ja (35.0 mg, 60% yield): colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.3 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.36−7.27 (m, 3H), 3.39 (q, J = 7.1 Hz, 2H), 3.25 (q, J = 7.1 Hz, 2H), 2.39 (s, 3H), 1.10 (t, J = 7.1 Hz, 3H), 1.01 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 196.9, 170.1, 138.3, 137.3, 137.1, 135.3, 133.0, 131.4, 130.23, 130.17 (2C), 128.2 (2C), 126.7, 43.2, 38.8, 21.2, 13.7, 12.1; HRMS (FTMS-ESI) calcd for C19H22NO2 [M + H]+ 296.1645, found 296.1644. 2-Benzoyl-4-chloro-N,N-diethylbenzamide (3ka). By following the general procedure, the reaction of 1k (42.3 mg, 0.2 mmol) with 2a (60.0 mg, 0.4 mmol) gave 3ka (46.1 mg, 73% yield): yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.3 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.54−7.43 (m, 4H), 7.34 (d, J = 8.1 Hz, 1H), 3.41 (q, J = 6.8 Hz, 2H), 3.26 (q, J = 6.6 Hz, 2H), 1.12 (t, J = 7.1 Hz, 3H), 1.03 (t, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 195.4, 169.0, 138.9, 136.6 (2C), 134.4, 133.6, 130.8, 130.4 (2C), 129.7, 128.6 (2C), 128.2, 43.4, 39.1, 13.9, 12.2; HRMS (FTMS-ESI) calcd for C18H19ClNO2 [M + H]+ 316.1099, found 316.1096. 2-Benzoyl-N,N-diethyl-5-methylbenzamide (3la). By following the general procedure, the reaction of 1l (38.4 mg, 0.2 mmol) with 2a

EXPERIMENTAL SECTION

General Information. NMR spectra were recorded on a 400 MHz NMR spectrometer (400 MHz for 1H NMR; 100.6 MHz for 13C NMR). 1H NMR chemical shifts were determined relative to internal TMS at δ 0.0 ppm. 13C NMR chemical shifts were determined relative to CDCl3 at δ 77.16 ppm. Data for 1H NMR and 13C NMR are reported as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, q = quartet, br = broad). Highresolution mass spectra (HRMS) were measured with FTMS-ESI in a positive mode. 1a, 1i, 1l, 1n, 1p, 2a, and 2s were purchased from J&K, Adamas-beta, Aladdin, and TCI and used directly. 1b−1h, 1j, 1k, 1m, 1o, 2b−2r, and 4a−4d were prepared according to the reported protocols.12c,22 The solvent 1,2-dichloroethene (DCE) was purchased from Sinopharm Chemical Reagent Co. Ltd. (SCRC) and used directly. General Procedure for the Palladium-Catalyzed Decarboxylative ortho-Acylation of Tertiary Benzamides with αOxocarboxylic Acids. A mixture of benzamide 1 (0.2 mmol), αoxocarboxylic acid 2 (0.4 mmol), Pd(OAc)2 (4.6 mg, 0.02 mmol), K2S2O8 (108.1 mg, 0.4 mmol), and TfOH (4.0 μL, 0.04 mmol) in DCE (2 mL) was stirred at 70 °C for 24 h. After this, the reaction mixture was cooled to room temperature. Then, the reaction mixture was filtered through a silica gel plug with ethyl acetate as the eluent and evaporated in a vacuum. Product 3 was purified by column chromatography over silica gel using petroleum ether and ethyl acetate (3:1) as the eluent. 2-Benzoyl-N,N-dimethylbenzamide (3aa).13 By following the general procedure, the reaction of 1a (29.9 mg, 0.2 mmol) with 2a (59.8 mg, 0.4 mmol) gave 3aa (39 mg, 77% yield): light yellow solid; 1 H NMR (400 MHz, CDCl3) δ 7.82−7.78 (m, 2H), 7.60−7.53 (m, 3H), 7.48−7.40 (m, 4H), 2.94 (s, 3H), 2.91 (s, 3H). 2-Benzoyl-4-methoxy-N,N-dimethylbenzamide (3ba). By following the general procedure, the reaction of 1b (35.9 mg, 0.2 mmol) with 2a (60.2 mg, 0.4 mmol) gave 3ba (39.7 mg, 70% yield): light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.3 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.36 (d, J = 8.0 Hz, 1H), 7.08−7.03 (m, 2H), 3.84 (s, 3H), 2.89 (s, 3H), 2.85 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 196.7, 170.5, 159.6, 139.0, 137.0, 133.3, 130.1 (2C), 129.9, 129.0, 128.4 (2C), 116.3, 115.2, 55.7, 39.3, 35.0; HRMS (FTMS-ESI) calcd for C17H18NO3 [M + H]+ 284.1281, found 284.1278. 2-Benzoyl-N,N,4-trimethylbenzamide (3ca). By following the general procedure, the reaction of 1c (32.7 mg, 0.2 mmol) with 2a (60.1 mg, 0.4 mmol) gave 3ca (39.6 mg, 74% yield): colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.4 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 7.39−7.33 (m, 2H), 7.31 (d, J = 7.6 Hz, 1H), 2.89 (s, 6H), 2.40 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 197.1, 170.9, 138.7, 137.3, 137.2, 135.1, 133.1, 131.8, 130.4, 130.1 (2C), 128.4 (2C), 127.4, 39.2, 34.9, 21.4; HRMS (FTMS-ESI) calcd for C17H18NO2 [M + H]+ 268.1332, found 268.1331. 2-Benzoyl-4-fluoro-N,N-dimethylbenzamide (3da). By following the general procedure, the reaction of 1d (33.4 mg, 0.2 mmol) with 2a (60.4 mg, 0.4 mmol) gave 3da (37.2 mg, 69% yield): colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.7 Hz, 2H), 7.59 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 7.44−7.39 (m, 1H), 7.31−7.22 (m, 2H), 2.90 (s, 6H); 19F NMR (376 MHz, CDCl3) δ −110.76 to −110.85 (m, 1F); 13C NMR (101 MHz, CDCl3) δ 195.3, 169.6, 161.9 12721

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry (60.0 mg, 0.4 mmol) gave 3la (37.2 mg, 63% yield): colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.2 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.46−7.40 (m, 3H), 7.23 (d, J = 7.9 Hz, 1H), 7.20 (s, 1H), 3.44 (q, J = 7.1 Hz, 2H), 3.25 (q, J = 7.1 Hz, 2H), 2.44 (s, 3H), 1.10 (t, J = 7.1 Hz, 3H), 1.09 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 196.5, 170.3, 141.9, 138.7, 137.6, 133.8, 132.9, 130.5, 130.3 (2C), 128.7, 128.3 (2C), 127.6, 43.3, 38.9, 21.6, 13.8, 12.3; HRMS (FTMS-ESI) calcd for C19H22NO2 [M + H]+ 296.1645, found 296.1644. (2-Benzoylphenyl)(pyrrolidin-1-yl)methanone (3ma).13 By following the general procedure, the reaction of 1m (35.1 mg, 0.2 mmol) with 2a (60.0 mg, 0.4 mmol) gave 3ma (39.3 mg, 70% yield): yellow solid; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.3 Hz, 2H), 7.60− 7.52 (m, 3H), 7.49−7.41 (m, 4H), 3.42 (t, J = 6.6 Hz, 2H), 3.30 (t, J = 6.3 Hz, 2H), 1.92−1.84 (m, 4H); HRMS (FTMS-ESI) calcd for C18H18NO2 [M + H]+ 280.1332, found 280.1332. (2-Benzoylphenyl)(piperidin-1-yl)methanone (3na). By following the general procedure, the reaction of 1n (38.0 mg, 0.2 mmol) with 2a (60.0 mg, 0.4 mmol) gave 3na (21.2 mg, 37% yield): colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.8 Hz, 2H), 7.59−7.50 (m, 3H), 7.47−7.38 (m, 4H), 3.57−3.48 (m, 2H), 3.32−3.23 (m, 2H), 1.67−1.50 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 196.8, 169.1, 138.1, 137.3, 137.2, 133.1, 131.0, 130.2 (2C), 129.9, 128.34 (2C), 128.30, 127.2, 48.6, 42.7, 25.9, 25.3, 24.6; HRMS (FTMS-ESI) calcd for C19H20NO2 [M + H]+ 294.1489, found 294.1485. (2-Benzoylphenyl)(morpholino)methanone (3oa).13 By following the general procedure, the reaction of 1o (38.2 mg, 0.2 mmol) with 2a (60.3 mg, 0.4 mmol) gave 3oa (27.8 mg, 47% yield): colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.84−7.79 (m, 2H), 7.60−7.53 (m, 3H), 7.50−7.44 (m, 3H), 7.43−7.39 (m, 1H), 3.76−3.59 (m, 6H), 3.40− 3.31 (m, 2H); HRMS (FTMS-ESI) calcd for C18H18NO3 [M + H]+ 296.1281, found 296.1280. 2-Benzoyl-N-ethyl-N-methylbenzamide (3pa). By following the general procedure, the reaction of 1p (32.8 mg, 0.2 mmol) with 2a (61.3 mg, 0.4 mmol) gave 3pa (37.5 mg, 70% yield): yellow solid, mp 67−69 °C; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.6 Hz, 2H), 7.60−7.51 (m, 3H), 7.48−7.38 (m, 4H), 3.43 (q, J = 7.1 Hz, 1H), 3.27 (q, J = 7.1 Hz, 1H), 2.93 (s, 1.5H), 2.88 (s, 1.5H), 1.14 (t, J = 7.1 Hz, 1.5H), 1.06 (t, J = 7.1 Hz, 1.5H); 13C NMR (101 MHz, CDCl3) δ 196.8 (0.5C), 196.7 (0.5C), 170.6 (0.5C), 170.1 (0.5C), 138.24 (0.5C), 138.16 (0.5C), 137.2 (0.5C), 137.1 (0.5C), 137.0 (0.5C), 136.9 (0.5C), 133.1, 131.2 (0.5C), 131.1 (0.5C), 130.3, 130.2, 130.04 (0.5C), 129.98 (0.5C), 128.42 (0.5C), 128.37 (2C), 128.3 (0.5C), 127.2 (0.5C), 127.0 (0.5C), 46.0 (0.5C), 42.0 (0.5C), 36.5 (0.5C), 31.8 (0.5C), 13.3 (0.5C), 11.6 (0.5C); HRMS (FTMS-ESI) calcd for C17H18NO2 [M + H]+ 268.1332, found 268.1325. 2-(4-Methoxybenzoyl)-N,N-dimethylbenzamide (3ab). By following the general procedure, the reaction of 1a (29.9 mg, 0.2 mmol) with 2b (72.2 mg, 0.4 mmol) gave 3ab (34.0 mg, 60% yield): light yellow solid, mp 81−82 °C; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.9 Hz, 2H), 7.57−7.50 (m, 2H), 7.44 (td, J = 7.5, 1.2 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 6.93 (d, J = 8.9 Hz, 2H), 3.87 (s, 3H), 2.95 (s, 3H), 2.90 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 195.5, 170.8, 163.8, 137.8, 137.4, 132.7 (2C), 130.8, 129.9, 129.6, 128.4, 127.3, 113.7 (2C), 55.6, 39.2, 34.9; HRMS (FTMS-ESI) calcd for C17H18NO3 [M + H]+ 284.1281, found 284.1280. N,N-Dimethyl-2-(4-methylbenzoyl)benzamide (3ac). By following the general procedure, the reaction of 1a (30.1 mg, 0.2 mmol) with 2c (65.7 mg, 0.4 mmol) gave 3ac (35.6 mg, 67% yield): light yellow solid, mp 73−74 °C; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.1 Hz, 2H), 7.57−7.51 (m, 2H), 7.47−7.39 (m, 2H), 7.25 (d, J = 8.1 Hz, 2H), 2.94 (s, 3H), 2.90 (s, 3H), 2.41 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 196.5, 170.8, 144.1, 138.0, 137.1, 134.5, 131.1, 130.4 (2C), 129.9, 129.1 (2C), 128.4, 127.3, 39.2, 34.9, 21.8; HRMS (FTMS-ESI) calcd for C17H18NO2 [M + H]+ 268.1332, found 268.1332. 2-(4-Fluorobenzoyl)-N,N-dimethylbenzamide (3ad). By following the general procedure, the reaction of 1a (30.1 mg, 0.2 mmol) with 2d (67.2 mg, 0.4 mmol) gave 3ad (35.9 mg, 66% yield): light yellow solid, mp 80−82 °C; 1H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 8.7, 5.5 Hz, 2H), 7.56 (td, J = 7.4, 1.4 Hz, 1H), 7.53−7.49 (m, 1H), 7.46 (td, J

= 7.5, 1.1 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.13 (t, J = 8.6 Hz, 2H), 2.96 (s, 3H), 2.92 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −104.78 to −110.86 (m, 1F); 13C NMR (101 MHz, CDCl3) δ 195.3, 170.6, 165.9 (d, JC−F = 255.2 Hz), 138.0, 136.9, 133.4 (d, JC−F = 2.9 Hz), 132.9 (2C, d, JC−F = 9.4 Hz), 131.2, 129.6, 128.5, 127.4, 115.6 (2C, d, JC−F = 21.9 Hz), 39.2, 34.9; HRMS (FTMS-ESI) calcd for C16H15FNO2 [M + H]+ 272.1081, found 272.1081. 2-(4-Chlorobenzoyl)-N,N-dimethylbenzamide (3ae). By following the general procedure, the reaction of 1a (30.2 mg, 0.2 mmol) with 2e (73.8 mg, 0.4 mmol) gave 3ae (38.5 mg, 67% yield): light yellow solid, mp 97−98 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.5 Hz, 2H), 7.57 (td, J = 7.4, 1.5 Hz, 1H), 7.53−7.49 (m, 1H), 7.47 (dd, J = 7.3, 0.9 Hz, 1H), 7.45−7.39 (m, 3H), 2.96 (s, 3H), 2.91 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 195.6, 170.6, 139.7, 138.0, 136.6, 135.4, 131.6 (2C), 131.4, 129.7, 128.8 (2C), 128.6, 127.4, 39.2, 34.9; HRMS (FTMS-ESI) calcd for C16H15ClNO2 [M + H]+ 288.0786, found 288.0786. 2-(4-Bromobenzoyl)-N,N-dimethylbenzamide (3af). By following the general procedure, the reaction of 1a (30.6 mg, 0.2 mmol) with 2f (92.0 mg, 0.4 mmol) gave 3af (33.2 mg, 50% yield): light yellow solid, mp 118−119 °C; 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.6 Hz, 2H), 7.60 (d, J = 8.6 Hz, 2H), 7.57 (td, J = 7.4, 1.5 Hz, 1H), 7.51 (dd, J = 7.6, 1.1 Hz, 1H), 7.46 (td, J = 7.5, 1.2 Hz, 1H), 7.42 (d, J = 7.5 Hz, 1H), 2.96 (s, 3H), 2.91 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 195.8, 170.5, 138.1, 136.6, 135.8, 131.75 (2C), 131.68 (2C), 131.4, 129.8, 128.6, 128.4, 127.4, 39.2, 34.9; HRMS (FTMS-ESI) calcd for C16H15BrNO2 [M + H]+ 332.0281, found 332.0278. N,N-Dimethyl-2-(4-(trifluoromethyl)benzoyl)benzamide (3ag). By following the general procedure, the reaction of 1a (30.0 mg, 0.2 mmol) with 2g (87.2 mg, 0.4 mmol) gave 3ag (44.4 mg, 70% yield): light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.1 Hz, 2H), 7.73 (d, J = 8.1 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.48 (t, J = 7.4 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 2.96 (s, 3H), 2.93 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −63.08 (s, 3F); 13 C NMR (101 MHz, CDCl3) δ 195.7, 170.4, 140.0, 138.2, 136.2, 134.2 (q, JC−F = 32.7 Hz), 131.7, 130.3 (2C), 129.9, 128.6, 127.4, 125.4 (2C, q, JC−F = 3.7 Hz), 123.6 (q, JC−F = 272.8 Hz), 39.1, 34.8; HRMS (FTMS-ESI) calcd for C17H15F3NO2 [M + H]+ 322.1049, found 322.1044. 2-(3-Methoxybenzoyl)-N,N-dimethylbenzamide (3ah). By following the general procedure, the reaction of 1a (30.2 mg, 0.2 mmol) with 2h (72.1 mg, 0.4 mmol) gave 3ah (34.9 mg, 62% yield): yellow solid, mp 111−113 °C; 1H NMR (400 MHz, CDCl3) δ 7.59−7.53 (m, 2H), 7.48−7.39 (m, 2H), 7.39−7.31 (m, 3H), 7.15−7.10 (m, 1H), 3.84 (s, 3H), 2.97 (s, 3H), 2.92 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 196.5, 170.8, 159.7, 138.4, 138.3, 136.9, 131.3, 130.1, 129.4, 128.4, 127.4, 123.4, 120.0, 114.0, 55.6, 39.2, 34.9; HRMS (FTMS-ESI) calcd for C17H18NO3 [M + H]+ 284.1281, found 284.1281. 2-(3-Chlorobenzoyl)-N,N-dimethylbenzamide (3ai). By following the general procedure, the reaction of 1a (30.1 mg, 0.2 mmol) with 2i (74.4 mg, 0.4 mmol) gave 3ai (36.4 mg, 63% yield): light yellow solid, mp 94−95 °C; 1H NMR (400 MHz, CDCl3) δ 7.78 (t, J = 1.8 Hz, 1H), 7.67 (dt, J = 7.7, 1.2 Hz, 1H), 7.61−7.52 (m, 3H), 7.47 (td, J = 7.5, 1.2 Hz), 7.42 (d, J = 7.5 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 2.97 (s, 3H), 2.93 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 195.4, 170.5, 138.7, 138.2, 136.4, 134.7, 133.1, 131.5, 129.92, 129.90, 129.8, 128.6, 128.5, 127.4, 39.2, 34.9; HRMS (FTMS-ESI) calcd for C16H15ClNO2 [M + H]+ 288.0786, found 288.0789. 2-(3-Bromobenzoyl)-N,N-dimethylbenzamide (3aj). By following the general procedure, the reaction of 1a (29.9 mg, 0.2 mmol) with 2j (91.6 mg, 0.4 mmol) gave 3aj (49.6 mg, 75% yield): light yellow solid, mp 121−122 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 7.74− 7.68 (m, 2H), 7.58 (td, J = 7.4, 1.0 Hz, 1H), 7.54 (d, J = 6.8 Hz, 1H), 7.48 (t, J = 7.2 Hz, 1H), 7.42 (d, J = 7.5 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H), 2.97 (s, 3H), 2.94 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 195.3, 170.5, 139.0, 138.2, 136.4, 136.0, 132.8, 131.5, 130.0, 129.9, 128.9, 128.6, 127.4, 122.7, 39.2, 34.9; HRMS (FTMS-ESI) calcd for C16H15BrNO2 [M + H]+ 332.0281, found 332.0281. 2-(3-Iodobenzoyl)-N,N-dimethylbenzamide (3ak). By following the general procedure, the reaction of 1a (30.1 mg, 0.2 mmol) with 2k 12722

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry

2-(2-Naphthoyl)-N,N-dimethylbenzamide (3ar). By following the general procedure, the reaction of 1a (30.3 mg, 0.2 mmol) with 2r (80.7 mg, 0.4 mmol) gave 3ar (42.5 mg, 70% yield): light yellow solid, mp 144−146 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H), 7.98− 7.86 (m, 4H), 7.64−7.57 (m, 3H), 7.56−7.48 (m, 2H), 7.45 (d, J = 7.9 Hz, 1H), 2.95 (s, 3H), 2.92 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 196.8, 170.8, 138.2, 137.2, 135.7, 134.4, 132.7, 132.3, 131.3, 130.2, 129.8, 128.7, 128.52, 128.47, 127.9, 127.4, 126.9, 125.3, 39.3, 34.9; HRMS (FTMS-ESI) calcd for C20H18NO2 [M + H]+ 304.1332, found 304.1332. General Procedure for the Palladium-Catalyzed Decarboxylative ortho-Acylation of Tertiary Benzamides with Pyruvic Acid (2s). A mixture of benzamide 1a (1i or 1m, 0.5 mmol), pyruvic acid (2s) (1.0 mmol), Pd(OAc)2 (11.5 mg, 0.05 mmol), Na2S2O8 (238.1 mg, 1.0 mmol), AgOAc (41.5 mg, 0.25 mmol), and TfOH (10 μL, 0.1 mmol) in DCE (2.5 mL) was stirred at 100 °C for 48 h. The reaction mixture was subsequently cooled to room temperature. Then, the reaction mixture was filtered through a silica gel plug with ethyl acetate as the eluent and evaporated in a vacuum. The crude product was purified by column chromatography over silica gel using petroleum ether and ethyl acetate (1:1 to 1:2) as the eluent to give product 3as (3is or 3ms). 2-Acetyl-N,N-dimethylbenzamide (3as). By following the general procedure, the reaction of 1a (74.5 mg, 0.5 mmol) with 2s (88.1 mg, 1.0 mmol) gave 3as (42.1 mg, 44% yield): white solid, mp 72−73 °C; 1 H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.7 Hz, 1H), 7.57 (td, J = 7.4, 0.8 Hz, 1H), 7.47 (td, J = 7.6, 1.0 Hz, 1H), 7.30 (d, J = 7.0 Hz, 1H), 3.14 (s, 3H), 2.77 (s, 3H), 2.60 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.8, 171.9, 137.8, 135.0, 132.8, 129.7, 128.8, 127.3, 38.5, 34.9, 27.7; HRMS (FTMS-ESI) calcd for C11H13NO2Na [M + Na]+ 214.0844, found 214.0842. 2-Acetyl-N,N-diethylbenzamide (3is). By following the general procedure, the reaction of 1i (88.6 mg, 0.5 mmol) with 2s (88.1 mg, 1.0 mmol) gave 3is (51.5 mg, 47% yield): yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 7.8, 0.5 Hz, 1H), 7.55 (td, J = 7.5, 1.0 Hz, 1H), 7.46 (td, J = 7.6, 1.2 Hz, 1H), 7.29 (dd, J = 7.5, 0.7 Hz, 1H), 3.58 (q, J = 7.1 Hz, 2H), 3.09 (q, J = 7.1 Hz, 2H), 2.59 (s, 3H), 1.32 (t, J = 7.1 Hz, 3H), 1.03 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 198.6, 170.9, 138.0, 134.8, 132.4, 129.6, 128.5, 127.1, 42.6, 38.7, 27.7, 13.5, 12.1; HRMS (FTMS-ESI) calcd for C13H17NO2Na [M + Na]+ 242.1157, found 242.1156. 1-(2-(Pyrrolidine-1-carbonyl)phenyl)ethan-1-one (3ms). By following the general procedure, the reaction of 1m (87.6 mg, 0.5 mmol) with 2s (88.1 mg, 1.0 mmol) gave 3ms (38.0 mg, 35% yield): yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.7 Hz, 1H), 7.56 (td, J = 7.4, 0.7 Hz, 1H), 7.47 (td, J = 7.6, 0.9 Hz, 1H), 7.33 (dd, J = 7.5, 0.6 Hz, 1H), 3.68 (t, J = 6.9 Hz, 2H), 3.09 (t, J = 6.7 Hz, 2H), 2.60 (s, 3H), 2.12−1.93 (m, 2H), 1.92−1.84 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 199.0, 170.1, 138.4, 134.8, 132.7, 129.5, 128.8, 127.2, 48.5, 45.6, 27.8, 25.9, 24.6; HRMS (FTMS-ESI) calcd for C13H15NO2Na [M + Na]+ 240.1000, found 240.1003. General Procedure for the Palladium-Catalyzed Decarboxylative ortho-Acylation of Secondary Benzamides 4 with αOxocarboxylic Acids 2. A mixture of secondary benzamide 4 (0.2 mmol), α-oxocarboxylic acid 2 (0.4 mmol), Pd(OAc)2 (4.6 mg, 0.02 mmol), K2S2O8 (108.1 mg, 0.4 mmol), and TfOH (4.0 μL, 0.04 mmol) or TsOH (7.6 mg, 0.04 mmol) in DCE (2 mL) was stirred at 70 °C for 24 h. After this, the reaction mixture was subsequently cooled to room temperature. Then, the reaction mixture was filtered through a silica gel plug with ethyl acetate as the eluent and evaporated in a vacuum. Products 5 were purified by column chromatography over silica gel using petroleum ether and ethyl acetate (6:1) as the eluent. 3-Hydroxy-2-methyl-3-phenylisoindolin-1-one (5aa). By following the general procedure, the reaction of 1a (27.6 mg, 0.2 mmol) with 2a (60.7 mg, 0.4 mmol) gave 5aa (20.4 mg, 43% yield for TfOH; 36.4 mg, 76% yield for TsOH): white solid, mp 181−182 °C; 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 7.5 Hz, 1H), 7.47 (td, J = 7.5, 1.0 Hz, 1H), 7.39−7.29 (m, 7H), 4.50 (brs, 1H), 2.62 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.1, 149.1, 138.1, 132.7, 130.2, 129.5, 128.8

(110.4 mg, 0.4 mmol) gave 3ak (49.3 mg, 65% yield): light yellow solid, mp 139−140 °C; 1H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H), 7.90 (d, J = 7.9 Hz, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.58 (t, J = 7.4 Hz, 1H), 7.53 (d, J = 7.3 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.42 (d, J = 7.7 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 2.97 (s, 3H), 2.93 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 195.3, 170.5, 141.8, 139.0, 138.6, 138.3, 136.4, 131.5, 130.1, 129.9, 129.5, 128.6, 127.4, 94.1, 39.2, 34.9; HRMS (FTMS-ESI) calcd for C16H15INO2 [M + H]+380.0142, found 380.0142. N,N-Dimethyl-2-(3-(trifluoromethyl)benzoyl)benzamide (3al). By following the general procedure, the reaction of 1a (30.8 mg, 0.2 mmol) with 2l (87.3 mg, 0.4 mmol) gave 3al (40.3 mg, 63% yield): light yellow solid, mp 92−93 °C; 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.96 (d, J = 7.7 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.60 (t, J = 7.8 Hz, 2H), 7.53 (d, J = 7.4 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 7.44 (d, J = 7.5 Hz, 1H), 2.96 (s, 3H), 2.95 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −62.74 (s, 3F); 13C NMR (101 MHz, CDCl3) δ 195.3, 170.3, 138.2, 137.7, 136.2, 133.5, 131.6, 130.9 (q, JC−F = 33.0 Hz), 129.8, 129.4 (q, JC−F = 3.5 Hz), 129.0, 128.6, 127.4, 126.4 (q, JC−F = 3.8 Hz), 123.7 (q, JC−F = 272.6 Hz), 39.1, 34.8; HRMS (FTMS-ESI) calcd for C17H15F3NO2 [M + H]+ 322.1049, found 322.1051. 2-(2-Methoxybenzoyl)-N,N-dimethylbenzamide (3am). By following the general procedure, the reaction of 1a (30.5 mg, 0.2 mmol) with 2m (67.2 mg, 0.4 mmol) gave 3am (31.4 mg, 56% yield): light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.57−7.42 (m, 4H), 7.42−7.34 (m, 2H), 7.02 (t, J = 7.5 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 3.71 (s, 3H), 2.99 (s, 3H), 2.83 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 196.1, 171.1, 158.1, 137.6, 136.8, 133.0, 132.1, 130.9, 130.8, 128.4, 128.2, 127.2, 120.6, 111.6, 55.8, 38.7, 34.9; HRMS (FTMS-ESI) calcd for C17H18NO3 [M + H]+ 284.1281, found 284.1282. N,N-Dimethyl-2-(2-methylbenzoyl)benzamide (3an). By following the general procedure, the reaction of 1a (30.4 mg, 0.2 mmol) with 2n (65.9 mg, 0.4 mmol) gave 3an (31.9 mg, 60% yield): yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.55 (td, J = 7.4, 1.3 Hz, 1H), 7.48 (dd, J = 7.6, 0.9 Hz, 1H), 7.43−7.32 (m, 4H), 7.26 (d, J = 7.1 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 3.00 (s, 3H), 2.90 (s, 3H), 2.42 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.7, 171.0, 138.3, 138.2, 137.9, 137.4, 131.9, 131.3, 131.2, 130.9, 130.1, 128.6, 127.2, 125.2, 39.0, 34.8, 20.5; HRMS (FTMS-ESI) calcd for C17H18NO2 [M + H]+ 268.1332, found 268.1332. 2-(2-Chlorobenzoyl)-N,N-dimethylbenzamide (3ao). By following the general procedure, the reaction of 1a (30.4 mg, 0.2 mmol) with 2o (74.0 mg, 0.4 mmol) gave 3ao (40.4 mg, 70% yield): light yellow solid, mp 87−88 °C; 1H NMR (400 MHz, CDCl3) δ 7.60 (td, J = 7.5, 1.3 Hz, 1H), 7.51 (dd, J = 7.8, 0.8 Hz, 1H), 7.47−7.32 (m, 6H), 3.05 (s, 3H), 2.87 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 195.1, 170.9, 138.3, 138.0, 134.8, 133.1, 131.9, 131.84, 131.77, 130.5, 130.2, 128.8, 127.5, 126.8, 38.7, 34.9; HRMS (FTMS-ESI) calcd for C16H15ClNO2 [M + H]+ 288.0786, found 288.0783. 2-(3,4-Dimethylbenzoyl)-N,N-dimethylbenzamide (3ap). By following the general procedure, the reaction of 1a (30.8 mg, 0.2 mmol) with 2p (71.3 mg, 0.4 mmol) gave 3ap (32.7 mg, 58% yield): light yellow solid, mp 99−101 °C; 1H NMR (400 MHz, CDCl3) δ 7.60 (s, 1H), 7.57−7.50 (m, 3H), 7.47−7.39 (m, 2H), 7.20 (d, J = 7.8 Hz, 1H), 2.96 (s, 3H), 2.91 (s, 3H), 2.32 (s, 3H), 2.29 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 196.7, 170.8, 142.8, 138.1, 137.2, 136.8, 134.9, 131.3, 131.0, 129.9, 129.6, 128.3, 128.2, 127.3, 39.2, 34.9, 20.2, 19.8; HRMS (FTMS-ESI) calcd for C18H20NO2 [M + H]+ 282.1489, found 282.1488. 2-(3,4-Dichlorobenzoyl)-N,N-dimethylbenzamide (3aq). By following the general procedure, the reaction of 1a (30.2 mg, 0.2 mmol) with 2q (87.6 mg, 0.4 mmol) gave 3aq (46.0 mg, 72% yield): light yellow solid, mp 129−131 °C; 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 2.0 Hz, 1H), 7.63 (dd, J = 8.3, 2.0 Hz, 1H), 7.61−7.56 (m, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.52−7.45 (m, 2H), 7.43 (d, J = 7.4 Hz, 1H), 2.98 (s, 3H), 2.94 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 194.5, 170.4, 138.2, 137.8, 136.7, 136.2, 133.1, 131.9, 131.6, 130.6, 129.7, 129.3, 128.7, 127.5, 39.2, 35.0; HRMS (FTMS-ESI) calcd for C16H14Cl2NO2 [M + H]+ 322.0396, found 322.0396. 12723

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry

4-Phenylphthalazin-1(2H)-one (7aa): 19 light yellow solid; 1H NMR (400 MHz, DMSO-d6) δ 12.86 (s, 1H), 8.38−8.32 (m, 1H), 7.94−7.87 (m, 2H), 7.71−7.66 (m, 1H), 7.62−7.53 (m, 5H). Synthesis and Characterization of Product 8aa. A mixture of 3aa (25.3 mg, 0.1 mmol), NH2OH·HCl (69.5 mg, 1.0 mmol), and Et3N (139 μL, 1.0 mmol) was loaded into a sealed tube equipped with a Teflon-coated magnetic stir bar. EtOH (1 mL) was added into the tube. The tube was stirred at 80 °C for 24 h. After cooling the mixture to room temperature, the solvent was removed in a vacuum. Column chromatography of the residue over silica gel using petroleum ether and ethyl acetate (6:1) as the eluent gave product 8aa (15.6 mg, 70% yield). 4-Phenyl-1H-benzo[d][1,2]oxazin-1-one (8aa): 20 white solid; 1H NMR (400 MHz, CDCl3) δ 8.50−8.44 (m, 1H), 7.92−7.84 (m, 2H), 7.63−7.53 (m, 6H). Synthesis and Characterization of Product 9aa. A mixture of 3a (25.7 mg, 0.1 mmol) and NH4OAc (154.2 mg, 2.0 mmol) was loaded into a sealed tube equipped with a Teflon-coated magnetic stir bar. EtOH (1 mL) was added into the tube. The tube was stirred at 100 °C for 24 h. After cooling the mixture to room temperature, the solvent was removed in a vacuum. Column chromatography of the residue over silica gel using petroleum ether and ethyl acetate (3:1) as the eluent afforded product 9aa (21.7 mg, 86% yield). 3-Ethoxy-3-phenylisoindolin-1-one (9aa): white solid, mp 128− 130 °C; 1H NMR (400 MHz, CDCl3) δ 7.85−7.81 (m, 1H), 7.58− 7.54 (m, 2H), 7.52 (td, J = 7.4, 1.4 Hz, 1H), 7.47 (td, J = 7.4, 1.4 Hz, 1H), 7.37−7.27 (m, 4H), 6.60 (s, 1H), 3.55−3.46 (m, 1H), 3.15−3.05 (m, 1H), 1.21 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 169.8, 147.3, 140.3, 133.1, 131.0, 129.7, 128.8 (2C), 128.7, 125.7 (2C), 123.9, 123.3, 91.9, 58.6, 15.4; HRMS (FTMS-ESI) calcd for C16H15NO2Na [M + Na]+ 276.1000, found 276.0999. Preliminary Mechanistic Studies. 1. Trapping Experiment with TEMPO. A mixture of benzamide 1a (29.9 mg, 0.2 mmol), 2a (60 mg, 0.4 mmol), Pd(OAc)2 (4.6 mg, 0.02 mmol), K2S2O8 (108.1 mg, 0.4 mmol), TfOH (4.0 μL, 0.04 mmol), and TEMPO (62.5 mg, 0.4 mmol) in DCE (2 mL) was stirred at 70 °C for 24 h. After this, the reaction mixture was subsequently cooled to room temperature, filtered through a silica gel plug with ethyl acetate as the eluent, and evaporated in a vacuum. Column chromatography of the residue over silica gel using petroleum ether and ethyl acetate (6:1) as the eluent provided product 10 (31.9 mg, 31% yield based on 2a). 2,2,6,6-Tetramethylpiperidin-1-yl Benzoate (10): 21 white solid; 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 7.9 Hz, 2H), 7.57 (d, J = 7.3 Hz, 1H), 7.46 (d, J = 7.6 Hz, 2H), 1.84−1.66 (m, 3H), 1.62−1.56 (m, 2H), 1.50−1.42 (m, 1H), 1.28 (s, 6H), 1.12 (s, 6H). 2. Kinetic Isotope Effect Experiment. A mixture of benzamide 1a (14.9 mg, 0.1 mmol), [D5]-1a (15.4 mg, 0.1 mmol), 2a (60 mg, 0.4 mmol), Pd(OAc)2 (4.6 mg, 0.02 mmol), K2S2O8 (108.1 mg, 0.4 mmol), and TfOH (4.0 μL, 0.04 mmol) in DCE (2 mL) was stirred at 70 °C for 24 h. After this, the reaction mixture was subsequently cooled to room temperature, filtered through a silica gel plug with ethyl acetate as the eluent, and evaporated in a vacuum. The residue was purified by column chromatography over silica gel using petroleum ether and ethyl acetate (3:1) as the eluent to afford a mixture of 3aa and [D4]-3aa (22.9 mg, 45% yield), which was analyzed by 1H NMR spectroscopy. 3. Intermolecular Competition Experiments. (a) A mixture of benzamide 1b (35.8 mg, 0.2 mmol), 1e (36.7 mg, 0.2 mmol), 2a (30 mg, 0.2 mmol), Pd(OAc)2 (4.6 mg, 0.02 mmol), K2S2O8 (108.1 mg, 0.4 mmol), and TfOH (4.0 μL, 0.04 mmol) in DCE (2 mL) was stirred at 70 °C for 24 h. After this, the reaction mixture was subsequently cooled to room temperature, filtered through a silica gel plug with ethyl acetate as the eluent, and evaporated in a vacuum. The residue was purified by column chromatography over silica gel using petroleum ether and ethyl acetate (3:1) as the eluent to afford 3ba (24.1 mg, 43% yield) and 3ea (10.1 mg, 18% yield). (b) A mixture of benzamide 1a (29.8 mg, 0.2 mmol), 2-(4methoxyphenyl)-2-oxoacetic acid (2b) (36.2 mg, 0.2 mmol), 2-

(2C), 128.6, 126.1 (2C), 123.2, 122.9, 91.2, 24.0; HRMS (FTMS-ESI) calcd for C15H14NO2 [M + H]+ 240.1019, found 240.0999. 3-Hydroxy-2,5-dimethyl-3-phenylisoindolin-1-one (5ba). By following the general procedure, the reaction of 1b (30.0 mg, 0.2 mmol) with 2a (60.8 mg, 0.4 mmol) gave 5ba (22.3 mg, 44% yield for TfOH; 41.4 mg, 82% yield for TsOH): white solid, mp 177−178 °C; 1H NMR (400 MHz, CDCl3) δ 7.41−7.29 (m, 6H), 7.14−7.09 (m, 2H), 4.89 (s, 1H), 2.56 (s, 3H), 2.35 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.3, 149.6, 143.5, 138.4, 130.1, 128.7 (2C), 128.4, 127.5, 126.1 (2C), 123.4, 123.0, 91.0, 24.0, 22.0; HRMS (FTMS-ESI) calcd for C16H16NO2 [M + H]+ 254.1176, found 254.1161. 2-Ethyl-3-hydroxy-3-phenylisoindolin-1-one (5ca). By following the general procedure, the reaction of 1c (29.8 mg, 0.2 mmol) with 2a (60.1 mg, 0.4 mmol) gave 5ca (26.3 mg, 52% yield for TfOH; 39.4 mg, 78% yield for TsOH): white solid, mp 147−148 °C; 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 7.3 Hz, 1H), 7.46 (t, J = 7.2 Hz, 1H), 7.42−7.36 (m, 3H), 7.35−7.29 (m, 3H), 7.26 (d, J = 6.6 Hz, 1H), 4.09 (s, 1H), 3.48−3.37 (m, 1H), 3.11−3.00 (m, 1H), 0.97 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 167.8, 149.2, 138.8, 132.7, 130.7, 129.5, 128.6 (2C), 128.5, 126.4 (2C), 123.2, 122.8, 91.5, 34.3, 14.3; HRMS (FTMS-ESI) calcd for C16H16NO2 [M + H]+ 254.1176, found 254.1165. 3-Hydroxy-2-isopropyl-3-phenylisoindolin-1-one (5da). By following the general procedure, the reaction of 1d (32.6 mg, 0.2 mmol) with 2a (60.1 mg, 0.4 mmol) gave 5da (25.1 mg, 47% yield for TfOH; 42.1 mg, 79% yield for TsOH): white solid, mp 163−165 °C; 1 H NMR (400 MHz, CDCl3) δ 7.74−7.69 (m, 1H), 7.46−7.40 (m, 4H), 7.36−7.30 (m, 3H), 7.20−7.15 (m, 1H), 3.61 (heptet, J = 6.9 Hz, 1H), 3.28 (s, 1H), 1.42 (d, J = 6.8 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 167.5, 148.8, 138.8, 132.5, 131.8, 129.6, 128.5, 128.4 (2C), 126.5 (2C), 123.2, 122.6, 91.9, 45.1, 21.4, 20.0; HRMS (FTMS-ESI) calcd for C17H18NO2 [M + H]+ 268.1293, found 268.1283. 3-Hydroxy-2,5-dimethyl-3-(p-tolyl)isoindolin-1-one (5bc). By following the general procedure, the reaction of 1b (29.8 mg, 0.2 mmol) with 2c (66.0 mg, 0.4 mmol) gave 5bc (24.0 mg, 45% yield for TfOH; 40.1 mg, 75% yield for TsOH): white solid, mp 176−177 °C; 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 7.6 Hz, 1H), 7.24 (d, J = 8.1 Hz, 2H), 7.16−7.08 (m, 4H), 4.77 (s, 1H), 2.56 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.3, 149.7, 143.4, 138.2, 135.4, 130.1, 129.4 (2C), 127.5, 126.0 (2C), 123.3, 123.0, 91.1, 23.9, 22.0, 21.2; HRMS (FTMS-ESI) calcd for C17H18NO2 [M + H]+ 268.1338, found 268.1336. 3-(4-Bromophenyl)-3-hydroxy-2,5-dimethylisoindolin-1-one (5bf). By following the general procedure, the reaction of 1b (29.8 mg, 0.2 mmol) with 2f (91.2 mg, 0.4 mmol) gave 5bf (26.5 mg, 40% yield for TfOH; 39.9 mg, 60% yield for TsOH): white solid, mp 194−196 °C; 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 7.7 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 7.7 Hz, 1H), 7.06 (s, 1H), 5.18 (s, 1H), 2.51 (s, 3H), 2.35 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.3, 149.1, 143.7, 137.6, 131.9 (2C), 130.2, 128.0 (2C), 127.3, 123.3, 123.0, 122.6, 90.7, 23.9, 22.0; HRMS (FTMS-ESI) calcd for C16H15BrNO2 [M + H]+ 332.0286, found 332.0283. Synthesis and Characterization of Product 6aa. A mixture of 3aa (25.3 mg, 0.1 mmol) and NaBH4 (5.7 mg, 0.15 mmol) in EtOH (1 mL) was stirred at room temperature for 3 h. The solvent was removed in a vacuum, and then the residue was separated by column chromatography over silica gel using petroleum ether and ethyl acetate (6:1) as the eluent to provide product 6aa (18.1 mg, 86% yield). 3-Phenylisobenzofuran-1(3H)-one (6aa): 18 light yellow solid; 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 7.7 Hz, 1H), 7.65 (td, J = 7.5, 0.9 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.40−7.35 (m, 3H), 7.33 (d, J = 7.7 Hz, 1H), 7.30−7.25 (m, 2H), 6.41 (s, 1H). Synthesis and Characterization of Product 7aa. A mixture of 3aa (25.9 mg, 0.1 mmol) and NH2NH2·H2O (29 μL, 0.5 mmol) was loaded into a sealed tube equipped with a Teflon-coated magnetic stir bar. EtOH (1 mL) was added into the tube. The tube was stirred at 80 °C for 24 h. After cooling the mixture to room temperature, the crude product was recrystallized from ethanol and diethyl ether to afford 7aa (20.2 mg, 91% yield). 12724

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725

Article

The Journal of Organic Chemistry

■

(10) For selected examples, see: (a) Yao, J.; Feng, R.; Wu, Z.; Liu, Z.; Zhang, Y. Adv. Synth. Catal. 2013, 355, 1517. (b) Miao, J.; Ge, H. Org. Lett. 2013, 15, 2930. (c) Wu, Y.; Sun, L.; Chen, Y.; Zhou, Q.; Huang, J.-W.; Miao, H.; Luo, H.-B. J. Org. Chem. 2016, 81, 1244. (d) Yao, J.-P.; Wang, G.-W. Tetrahedron Lett. 2016, 57, 1687. (11) For selected examples, see: (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893. (b) Laufer, R. S.; Dmitrienko, G. I. J. Am. Chem. Soc. 2002, 124, 1854. (c) Wang, X.; Fu, J.-m.; Snieckus, V. Helv. Chim. Acta 2012, 95, 2680. (12) For selected examples, see: (a) Thirunavukkarasu, V. S.; Hubrich, J.; Ackermann, L. Org. Lett. 2012, 14, 4210. (b) WencelDelord, J.; Nimphius, C.; Wang, H.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 13001. (c) Wencel-Delord, J.; Nimphius, C.; Patureau, F. W.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 2247. (d) Yang, Z.; Qiu, F.-C.; Gao, J.; Li, Z.-W.; Guan, B.-T. Org. Lett. 2015, 17, 4316. (e) Nareddy, P.; Jordan, F.; Brenner-Moyer, S. E.; Szostak, M. ACS Catal. 2016, 6, 4755. (f) Lied, F.; Lerchen, A.; Knecht, T.; MückLichtenfeld, C.; Glorius, F. ACS Catal. 2016, 6, 7839. (g) Nareddy, P.; Jordan, F.; Szostak, M. Chem. Sci. 2017, 8, 3204. (13) Park, J.; Park, E.; Kim, A.; Lee, Y.; Chi, K.-W.; Kwak, J. H.; Jung, Y. H.; Kim, I. S. Org. Lett. 2011, 13, 4390. (14) For a review, see: (a) Wang, G.-W. Top. Organomet. Chem. 2016, 55, 119. For selected examples, see: (b) Wang, G.-W.; Yuan, T.T.; Li, D.-D. Angew. Chem., Int. Ed. 2011, 50, 1380. (c) Li, Z.-Y.; Wang, G.-W. Org. Lett. 2015, 17, 4866. (d) Li, Z.-Y.; Li, L.; Li, Q.-L.; Jing, K.; Xu, H.; Wang, G.-W. Chem. - Eur. J. 2017, 23, 3285. (15) A closely related palladium-catalyzed ortho-acylation of tertiary benzamides using arylglyoxylic acids was published after the original submission of this work to J. Org. Chem. See: Laha, J. K.; Patel, K. V.; Sharma, S. ACS Omega 2017, 2, 3806. (16) Xiao, B.; Fu, Y.; Xu, J.; Gong, T.-J.; Dai, J.-J.; Yi, J.; Liu, L. J. Am. Chem. Soc. 2010, 132, 468. (17) (a) Negishi, E.-I. Handbook of Organopalladium for Organic Synthesis; Wiley-Interscience, 2002; Vols. 1−2. (b) de Meijere, A. In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley−VCH: Weinheim, 2004; Vols. 1−2. (c) Tsuji, J. Palladium Reagents and Catalysts, 2nd ed.; Wiley: Chichester, 2004. (18) (a) Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring Compounds; Academic Press: New York, 1975; Vol. 1, p 249. (b) Ramachandran, P. V.; Chen, G.-M.; Brown, H. C. Tetrahedron Lett. 1996, 37, 2205. (c) Karthikeyan, J.; Parthasarathy, K.; Cheng, C.H. Chem. Commun. 2011, 47, 10461. (19) Botero Cid, H. M.; Tränkle, C.; Baumann, K.; Pick, R.; MiesKlomfass, E.; Kostenis, E.; Mohr, K.; Holzgrabe, U. J. Med. Chem. 2000, 43, 2155. (20) Csende, F.; Stájer, G. Heterocycles 2000, 53, 1379. (21) (a) Wang, H.; Guo, L.-N.; Wang, S.; Duan, X.-H. Org. Lett. 2015, 17, 3054. (b) Xu, N.; Liu, J.; Li, D.; Wang, L. Org. Biomol. Chem. 2016, 14, 4749. (22) Wadhwa, K.; Yang, C.; West, P. R.; Deming, K. C.; Chemburkar, S. R.; Reddy, R. E. Synth. Commun. 2008, 38, 4434.

oxo-2-(4-(trifluoromethyl)phenyl)acetic acid (2g) (43.6 mg, 0.2 mmol), Pd(OAc)2 (4.6 mg, 0.02 mmol), K2S2O8 (108.1 mg, 0.4 mmol), and TfOH (4.0 μL, 0.04 mmol) in DCE (2 mL) was stirred at 70 °C for 24 h. After this, the reaction mixture was subsequently cooled to room temperature, filtered through a silica gel plug with ethyl acetate as the eluent, and evaporated in a vacuum. The residue was purified by column chromatography over silica gel using petroleum ether and ethyl acetate (3:1) as the eluent to afford 3ab (14.7 mg, 26% yield) and 3ag (21.9 mg, 34% yield).

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02552. NMR spectra of 3, 5, 6aa−9aa, and 10 as well as a mixture of 3aa and [D4]-3aa (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Guan-Wu Wang: 0000-0001-9287-532X Notes

The authors declare no competing financial interest.

■

REFERENCES

(1) For selected examples, see: (a) Madan, B.; Singh, I.; Kumar, A.; Prasad, A. K.; Raj, H. G.; Parmar, V. S.; Ghosh, B. Bioorg. Med. Chem. 2002, 10, 3431. (b) Ma, D.; Jiang, Y.; Chen, F.; Gong, L.-k.; Ding, K.; Xu, Y.; Wang, R.; Ge, A.; Ren, J.; Li, J.; Li, J.; Ye, Q. J. Med. Chem. 2006, 49, 456. (c) Deng, Y.; Chin, Y.-W.; Chai, H.; Keller, W. J.; Kinghorn, A. D. J. Nat. Prod. 2007, 70, 2049. (d) Singh, S.; Prasad, N. R.; Chufan, E. E.; Patel, B. A.; Wang, Y.-J.; Chen, Z.-S.; Ambudkar, S. V.; Talele, T. T. J. Med. Chem. 2014, 57, 4058. (2) (a) Olah, G. A. Friedel−Crafts Chemistry; Wiley: New York, 1973. (b) Sartori, G.; Maggi, R. Chem. Rev. 2006, 106, 1077. (3) For selected examples, see: (a) Rodríguez, N.; Goossen, L. J. Chem. Soc. Rev. 2011, 40, 5030. (b) Li, M.; Wang, C.; Ge, H. Org. Lett. 2011, 13, 2062. (c) Yang, K.; Zhang, C.; Wang, P.; Zhang, Y.; Ge, H. Chem. - Eur. J. 2014, 20, 7241. (d) Yang, K.; Chen, X.; Wang, Y.; Li, W.; Kadi, A. A.; Fun, H.-K.; Sun, H.; Zhang, Y.; Li, G.; Lu, H. J. Org. Chem. 2015, 80, 11065. (4) Gooßen, L. J.; Rudolphi, F.; Oppel, C.; Rodríguez, N. Angew. Chem., Int. Ed. 2008, 47, 3043. (5) (a) Fang, P.; Li, M.; Ge, H. J. Am. Chem. Soc. 2010, 132, 11898. (b) Li, M.; Ge, H. Org. Lett. 2010, 12, 3464. (6) For selected examples, see: (a) Kim, M.; Park, J.; Sharma, S.; Kim, A.; Park, E.; Kwak, J. H.; Jung, Y. H.; Kim, I. S. Chem. Commun. 2013, 49, 925. (b) Yang, Z.; Chen, X.; Liu, J.; Gui, Q.; Xie, K.; Li, M.; Tan, Z. Chem. Commun. 2013, 49, 1560. (c) Cai, H.-T.; Li, D.-D.; Liu, Z.; Wang, G.-W. Acta Chim. Sin. 2013, 71, 717. (7) For selected examples, see: (a) Li, H.; Li, P.; Tan, H.; Wang, L. Chem. - Eur. J. 2013, 19, 14432. (b) Li, H.; Li, P.; Zhao, Q.; Wang, L. Chem. Commun. 2013, 49, 9170. (c) Li, Z.-Y.; Li, D.-D.; Wang, G.-W. J. Org. Chem. 2013, 78, 10414. (8) For selected examples, see: (a) Wang, H.; Guo, L.-N.; Duan, X.H. Org. Lett. 2012, 14, 4358. (b) Park, J.; Kim, M.; Sharma, S.; Park, E.; Kim, A.; Lee, S. H.; Kwak, J. H.; Jung, Y. H.; Kim, I. S. Chem. Commun. 2013, 49, 1654. (c) Sharma, S.; Kim, A.; Park, E.; Park, J.; Kim, M.; Kwak, J. H.; Lee, S. H.; Jung, Y. H.; Kim, I. S. Adv. Synth. Catal. 2013, 355, 667. (9) For selected examples, see: (a) Pan, C.; Jin, H.; Liu, X.; Cheng, Y.; Zhu, C. Chem. Commun. 2013, 49, 2933. (b) Kim, M.; Mishra, N. K.; Park, J.; Han, S.; Shin, Y.; Sharma, S.; Lee, Y.; Lee, E.-K.; Kwak, J. H.; Kim, I. S. Chem. Commun. 2014, 50, 14249. 12725

DOI: 10.1021/acs.joc.7b02552 J. Org. Chem. 2017, 82, 12715−12725