Cyanoarenes are important structural motifs that form the core structures of numerous compounds, including dyes, herbicides, agrochemicals and natural products, as well as being important pharmacophores and synthetic building blocks ^{[1, 2, 3, 4, 5]}. Moreover, the cyano functionality of these compounds can be used as a valuable intermediate and effective precursor for the synthesis of various functionalized products such as aldehydes, ketones, amines, amides, amidines, benzoic acid derivatives, and heterocycles ^{[6, 7, 8, 9, 10]}. Therefore, the development of new mild and efficient methods for facile construction of aryl-CN bonds has attracted considerable attention in modern organic synthesis ^{[11, 12, 13, 14, 15, 16, 17, 18]}. Among the many different methods available for the direct synthesis of cyanoarenes, the transition-metal-catalyzed regioselective cyanation of C−H bonds has emerged as one of the most promising and economical ^{[19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46]}. Among the various transition-metals available for this reaction, Pd ^{[29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39]} and Cu ^{[40, 41, 42, 43, 44, 45, 46]} catalysts have been investigated extensively with a wide range of both metallic and nonmetallic cyano-group sources, including NaCN, CuCN, Zn(CN)₂, nitromethane, DMF, TMSCN, acetonitrile, isonitrile and N-cyano-N-phenyl-p-toluenesulfonamide (NCTS, 2). However, in contrast to the remarkable advances made in this field using Pd and Cu catalysts, there have been very few reports pertaining to Rh(III)-catalyzed cyanation reactions. In fact, to the best of our knowledge, only six examples of Rh(III)-catalyzed reactions for the direct construction of cyanoarenes have been reported to date by the groups of Fu ^[47], Anbarasan ^{[48, 49]}, Gu ^[50], Zhu ^[51] and Xu ^[52] (Scheme 1(a)-(c)). For this reason, further research is still needed to explore and develop new, efficient, selective and practical Rh(III)-catalyzed C−H bond cyanation reactions, because Rh(III)-based catalysts has been proven to perform just as effectively as any other transition metal catalyst in terms of their activity, selectivity, substrate scope and functional group tolerance ^{[53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66]}.

Scheme 1. Evolution of the Rh(III)-catalyzed C-H cyanation of arenes.

A suitable directing group (DG) is generally required to achieve Rh(III)-catalyzed C-H activation reactions. Furthermore, the use of a DG can be advantageous in terms of improving the regioselectivity and overall efficiency of the reaction. As a consequence, several versatile DGs have been developed, with the CONHOMe group playing a particularly prominent role ^{[67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83]}. Following on from the pioneering work of Yu et al. ^{[67, 68]} in 2008, significant progress has been made towards the development of a broad range of important synthetic transformations that proceed in a step- and atom-economical fashion using a CONHOMe moiety as part of a DG strategy.

With all of this in mind, it was envisioned that a CONHOMe-mediated C-H bond cyanation could be achieved using a suitable cyanating reagent as the coupling partner. As part of our ongoing interest in the development of Rh(III)-catalyzed and CONHOMe-mediated C-H activation reactions ^[83], we herein report the development of a Rh(III)-catalyzed reaction for the C-H bond cyanation of N-methoxybenzamides using NCTS as the efficient cyanating reagent (Scheme 1(d)).

All of the chemicals used in the current study were obtained from commercial suppliers and were dried and purified as necessary. The water used in this study was re-distillated and ion-free. Melting points were determined on a WRS-1B digital instrument without correction. ¹H and ¹³C NMR spectra were recorded on Varian Mercury-Plus 400 NMR instruments (¹H 400 MHz; ¹³C 100 MHz or ¹³C 125 MHz in CDCl₃. The multiplicities of the peaks have been reported as follows: s, singlet; brs, broad singlet; d, doublet; t, triplet; dd, doublet of doublets; m, multiplet. High-resolution mass spectra were measured on an Agilent G6230B mass spectrometer. Thin-layer chromatography was conducted on pre-coated silica gel 60 F254 plates (Merck). Silica gel 60H (200-300 mesh) manufactured by Qingdao Haiyang Chemical Group Co. was used for general chromatography.

A mixture of N-methoxybenzamide (1, 0.20 mmol), NCTS (2, 49.0 mg, 0.22 mmol), [Cp*RhCl₂]₂ (3 mg, 0.005 mmol, 2.5 mol %) and Ag₂CO₃ (54 mg, 0.2 mmol, 1.0 equiv.) in dioxane (1.0 mL) was stirred at 80 °C for 8 h. The mixture was then cooled to room temperature and the solvent removed under reduced pressure to give a residue, which was purified by column chromatography over silica gel to give the desired product 3.

2-Cyano-N-methoxybenzamide (3a). 75% yield as a white solid. M.p. 72-73 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.94 (d, J = 7.0 Hz, 1H), 7.85 (d, J = 6.8 Hz, 1H), 7.75-7.69 (m, 2H), 4.08 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 162.2, 153.8, 133.8, 132.8, 131.0, 128.4, 123.4, 122.2, 65.4; HRMS (ESI) calcd. for 177.0664 ([M+H]⁺), found 177.0663 ([M+H]⁺).

2-Cyano-N-methoxy-6-methylbenzamide (3b). 80% yield as a white solid. M.p. 67-68 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.78 (d, J = 7.6 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 4.07 (s, 3H), 2.70 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 163.2, 154.0, 138.0, 135.0, 133.2, 131.4, 125.2, 119.8, 65.4, 17.4; HRMS (ESI) calcd. for 191.0821 ([M+H]⁺), found 191.0820 ([M+H]⁺).

2-Chloro-6-cyano-N-methoxybenzamide (3c). 48% yield as a white solid. M.p. 126-126 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.90 (d, J = 6.8 Hz, 1H), 7.70-7.61 (m, 2H), 4.10 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 160.0, 134.6, 134.4, 131.6, 124.4, 120.8, 65.4; HRMS (ESI) calcd. for 211.0274, 213.0245 ([M+H]⁺), found 211.0273, 213.0244 ([M+H]⁺).

2-Cyano-N-methoxy-5-methylbenzamide (3d). 75% yield as a white solid. M.p. 87-88 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.91 (d, J = 7.6 Hz, 1H), 7.67 (s, 1H), 7.55 (d, J = 7.6 Hz, 1H), 4.10 (s, 3H), 2.52 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 162.4, 154.0, 143.8, 134.4, 128.4, 128.2, 1234.0, 122.2, 65.4, 22.0; HRMS (ESI) calcd. for 191.0821 ([M+H]⁺), found 191.0821 ([M+H]⁺).

2-Cyano-N,5-dimethoxybenzamide (3e-1) and 2-cyano-N,3- dimethoxybenzamide (3e-2). These two compounds were obtained as an inseparable mixture of regioisomers in a combined yield of 81% [mixture of 3e-1/3e-2 (4:1)] as a white solid. M.p. 90-91 °C; 3e-1: ¹H NMR (400 MHz, CDCl₃): δ 7.82 (d, J = 8.4 Hz, 1H), 7.31 (d, J = 1.6 Hz, 1H), 7.19 (dd, J = 8.4, 2.0 Hz, 1H), 4.06 (s, 3H), 3.91 (s, 3H); 3e-2: ¹H NMR (400 MHz, CDCl₃): δ 7.67-7.56 (m, 1H), 7.44 (d, J = 7.4 Hz, 1H), 7.22 (m, 1H), 4.09 (s, 3H), 4.04 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 163.6, 162.2, 156.4, 153.6, 134.2, 130.4, 129.8, 123.8, 123.0, 120.2, 116.4, 115.6, 107.6, 65.4, 56.0; HRMS (ESI) calcd. for 207.0770 ([M+H]⁺), found 207.0769 ([M+H]⁺).

2-Cyano-5-fluoro-N-methoxybenzamide (3f-1) and 2-cyano-3-fluoro-N-methoxybenzamide (3f-2). White solids in 20% (3f-1) and 56% (3f-2) yields. 3f-1: M.p. 108-109 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.01 (dd, J = 8.2, 4.4 Hz, 1H), 7.56 (dd, J = 7.0, 2.2 Hz, 1H), 7.43 (td, J = 8.7, 2.2 Hz, 1H), 4.10 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 165.6 (d, J = 255.6 Hz), 161.0, 153.0, 130.8 (d, J = 9.1 Hz), 125.0 (d, J = 9.0 Hz), 121.0 (d, J = 23.6 Hz), 111.2 (d, J = 24.8 Hz), 65.6; HRMS (ESI) calcd. for 195.0570 ([M+H]⁺), found 195.0569 ([M+H]⁺). 3f-2: M.p. 81-82 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.69 (m, 2H), 7.42 (m, 1H), 4.11 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 161.4, 157.8 (d, J = 261.0 Hz), 151.8, 134.8 (d, J = 7.6 Hz), 130.6, 121.8 (d, J = 19.6 Hz), 119.8 (d, J = 3.6 Hz), 65.38; HRMS (ESI) calcd. for 195.0570 ([M+H]⁺), found 195.0567 ([M+H]⁺).

5-Chloro-2-cyano-N-methoxybenzamide (3g). 46% yield as a white solid. M.p. 57-58 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.06 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 1.6 Hz, 1H), 7.73 (dd, J = 8.1, 1.6 Hz, 1H), 4.13 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 161.0, 139.2, 133.8, 130.0, 123.8, 123.6, 65.4; HRMS (ESI) calcd. for 211.0274, 213.0245 ([M+H]⁺), found 211.0273, 213.0243 ([M+H]⁺).

2-Cyano-N-methoxy-4-methylbenzamide (3h). 66% yield as a white solid. M.p. 47-48 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.73 (m, 2H), 7.48 (d, J = 7.6 Hz, 1H), 4.07 (s, 3H), 2.51 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 162.6, 154.0, 145.0, 133.4, 131.2, 125.8, 123.4, 122.6, 65.2, 22.2; HRMS(ESI) calcd. for 191.0821 ([M+H]⁺), found 191.0821 ([M+H]⁺).

2-Cyano-N,4-dimethoxybenzamide (3i). 77% yield as a white solid. M.p. 95-96 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.76 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 1.6 Hz, 1H), 7.15 (dd, J = 8.4, 2.0 Hz, 1H), 4.07 (s, 3H), 3.94 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 164.4, 162.4, 125.2, 120.4, 119.27, 106.8, 65.4, 56.0; HRMS (ESI) calcd. for 207.0770 ([M+H]⁺), found 207.0769 ([M+H]⁺).

2-Cyano-4-fluoro-N-methoxybenzamide (3j). 55% yield as a white solid. M.p. 102-103 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.87 (dd, J = 8.2, 4.8 Hz, 1H), 7.65 (dd, J = 7.5, 2.2 Hz, 1H), 7.37 (m, 1H), 4.09 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 166.2 (d, J = 255.9 Hz), 161.4, 152.6, 134.0, 126.0 (d, J = 9.5 Hz), 124.4, 120.0 (d, J = 23.6 Hz), 110.2 (d, J = 25.2 Hz), 65.4; HRMS (ESI) calcd. for 195.0570 ([M+H]⁺), found 195.0568 ([M+H]⁺).

4-Chloro-2-cyano-N-methoxybenzamide (3k). 30% yield as a white solid. M.p. 109-110 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.94 (d, J = 1.6 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.67 (dd, J = 8.0, 1.8 Hz, 1H), 4.09 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 161.4, 152.4, 140.4, 133.0, 126.6, 124.8, 122.8, 65.4; HRMS (ESI) calcd. for 211.0274, 213.0245 ([M+H]⁺), found 211.0273, 213.0241 ([M+H]⁺).

4-Bromo-2-cyano-N-methoxybenzamide (3l). 35% yield as a white solid. M.p. 132-133 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.10 (s, 1H), 7.83 (dd, J = 8.0, 1.6 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 4.08 (s, 3H); ¹³C NMR (125 MHz, CDCl₃): δ 161.6, 136.8, 135.8, 128.6, 127.0, 125.6, 124.8, 65.4; HRMS (ESI) calcd. for 254.9769, 256.9749([M+H]⁺), found 254.9767, 256.9745 ([M+H]⁺)

Methyl 3-cyano-4-(methoxycarbamoyl)benzoate (3m). 73% yield as a white solid. M.p. 160-161 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.61 (s, 1H), 8.38 (dd, J = 7.8, 1.0 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 4.11 (s, 3H), 4.00 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 165.4, 161.2, 135.2, 1334.0, 132.0, 123.6, 123.4, 65.4, 52.8; HRMS (ESI) calcd. for 235.0719 ([M+H]⁺), found 235.0717 ([M+H]⁺).

3-Cyano-N-methoxy-[1,1'-biphenyl]-4-carboxamide (3n). 86% yield as a white solid. M.p. 112-113 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.44 (s, 1H), 7.95 (m, 2H), 7.72-7.67 (m, 2H), 7.53 (t, J = 7.2 Hz, 2H), 7.50-7.46 (m, 1H), 4.17 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 162.0, 147.6, 139.0, 1312.0, 129.2, 129.0, 127.4, 126.2, 124.4, 122.0, 65.8; HRMS (ESI) calcd. for 253.0977 ([M+H]⁺), found 253.0976 ([M+H]⁺).

3-Cyano-N-methoxy-2-naphthamide (3o). 35% yield as a white solid. M.p. 135-136 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.43 (s, 1H), 8.37 (s, 1H), 8.05 (m, 2H), 7.75-7.65 (m, 2H), 4.14 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 162.0, 135.4, 134.8, 130.0, 129.8, 129.0, 128.6, 124.8, 122.0, 65.2; HRMS (ESI) calcd. for 227.0821 ([M+H]⁺), found 227.0820 ([M+H]⁺).

2-Cyano-N-methoxy-1-naphthamide (3p). 74% yield as a white solid. M.p. 135-136 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.96 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 7.6 Hz, 2H), 7.69 (m, 2H), 4.14 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 163.8, 154.2, 135.6, 134.6, 129.2, 128.6, 128.2, 124.6, 123.4, 117.8, 65.4; HRMS (ESI) calcd. for 227.0821 ([M+H]⁺), found 227.0821 ([M+H]⁺).

2-Cyano-N-methoxycyclohex-1-enecarboxamide (3q). 51% yield as a white solid. M.p. 131-132 °C; ¹H NMR (400 MHz, CDCl₃): δ 3.96 (m, 3H), 2.43 (m, 2H), 2.32 (m, 2H), 1.83-1.74 (m, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 166.0, 157.4, 141.0, 136.0, 65.2, 21.4, 20.2, 19.8; HRMS (ESI) calcd. for 181.0977 ([M+H]⁺), found 181.0978 ([M+H]⁺).

Given that the results of several previous studies have shown that NCTS, which is non-toxic, easy to prepare and handle and bench-stable, can be used as a highly efficient cyanating reagent for Rh(III)-catalyzed C-H activation reactions ^{[47, 48, 49, 50, 51]}, we commenced our study by investigating the reaction of N-methoxybenzamide (1a) with NCTS (2) in presence of several well-known Rh(III) catalysts to allow for the optimization of the reaction conditions (Table 1). Pleasingly, when [Cp*Rh(Cl)₂]₂ and CsOAc were employed as the catalyst and the additive, respectively (Table 1, entry 2), the reaction of 1a with 2 proceeded successfully in dioxane to deliver the expected cyanation product 3a in 46% yield. Furthermore, the replacement of CsOAc with Ag₂CO₃ gave an improved yield of 62%

Table 1 Optimization of the reaction conditions. Entry Catalyst (mol%) Additive (mol%) Solvent T (°C) Isolated yield (%) 1 [Cp*Rh(MeCN)3] (SbF6)2 (2.5) — Dioxane 100 0 2 [Cp*RhCl2]2 (2.5) CsOAc (100) Dioxane 100 46 3 [Cp*RhCl2]2 (2.5) Cu(OAc)2 (100) Dioxane 100 0 4 [Cp*RhCl2]2 (2.5) Ag2CO3 (100) Dioxane 100 62 5 [Cp*RhCl2]2 (2.5) Ag2CO3 (100) Dioxane 120 45 6 [Cp*RhCl2]2 (2.5) Ag2CO3 (100) Dioxane 80 75 7 a [Cp*RhCl2]2 (2.5) Ag2CO3 (100) Dioxane 50 20 8 [Cp*RhCl2]2 (2.5) Ag2CO3 (100) DCE 80 57 9 [Cp*RhCl2]2 (2.5) Ag2CO3 (100) THF 80 10 10 [Cp*RhCl2]2 (2.5) Ag2CO3 (100) MeCN 80 25 11 [Cp*RhCl2]2 (2.5) Ag2CO3 (20) Dioxane 80 36 12 b [Cp*RhCl2]2 (2.5) Ag2CO3 (100) Dioxane 80 67 Reaction conditions: substrate 1a (0.20 mmol), 2 (0.22 mmol), catalyst (2.5 mol%), the additive (100 mol%), solvent (1.0 mL), 8 h. a 24 h, 1a (20 mg) was recovered. b Performed on a 5.0 mmol scale.

Table 1 Optimization of the reaction conditions.

(Table 1, entry 4). Encouraged by this finding, we proceeded to

investigate the optimization of the reaction using a variety of different temperatures and solvents. As shown in Table 1, decreasing the reaction temperature to 80 °C led to an improvement in the yield to 75%, while raising the temperature to 120 °C or lowering to 50 °C resulted in a lower yield (Table 1, entries 5-7). Inferior results were also obtained in several other solvents, including DCE, THF and MeCN (Table 1, entries 8-10). Furthermore, reducing the amount of additive led to a significant decrease in the yield of the reaction (Table 1, entry 11). In summary, the optimal conditions for this reaction were found to include dioxane as the solvent with [Cp*RhCl₂]₂ (2.5 mol %) and Ag₂CO₃ (100 mol %) as the catalyst and additive, respectively, at 80 °C for 8 h under air. Finally, the reaction was amenable to scale up and could be readily conducted on a gram scale with the desired product 3a being isolated in a decent yield (Table 1, entry 12).

With the optimized conditions in hand, we proceeded to examine the substrate scope and limitations of this newly developed reaction using a series of N-methoxybenzamides. As demonstrated in Scheme 2, NCTS (2) underwent an efficient coupling reaction with a variety of functionalized N-methoxybenzamides to afford the corresponding aryl nitriles 3 in moderate to good yields. The presence of an electron-donating or electron-withdrawing group was well tolerated at the ortho- (3b-c), meta- (3d-g) or para- (3h-n) position. Importantly, the reaction also demonstrated good compatibility with a wide range of valuable functional groups, including methyl (3b, 3d and 3h), chloro (3c, 3g and 3k), methoxy (3e and 3i), fluoro (3f and 3j), ester (3m) and bromo (3l) substituents. Tolerance towards the Br, Cl and ester functional groups is especially noteworthy because these groups are useful intermediates and effective precursors for subsequent cross-coupling reactions. Notably, substrates 1d and 1g bearing methyl and Cl groups at the meta-position, respectively, afforded the corresponding cyanation products with complete regioselectivity. However, the meta-methoxy-substituted substrate 1e gave a 4:1 mixture of the regioisomeric products 3e-1 and 3e-2. In contrast, substrate 1f afforded a 1:3 mixture of the regioisomeric products 3f-1 and 3f-2, where the CN group was mainly attached at the more-hindered site. Taken together, these results revealed that the nature of the substituent at the meta-position played a critical role in determining the outcome of the reaction. Finally, we were pleased to find that this new cyanation reaction could also be applied to polyaromatic naphthalene and cyclohexene substrates, with the corresponding products being obtained in synthetically useful yields (35% for 3o, 74% for 3p and 51% for3q). The results therefore provide further illustration of the remarkably robust nature of our newly developed Rh(III)-catalyzed system.

Scheme 2. Scheme 2. Substrate scope of N-methoxybenzamides. Reaction conditions: substrates 1 (0.20 mmol), 2 (0.22 mmol), [Cp*RhCl2]2 (2.5 mol %), Ag2CO3 (100 mol %), dioxane (1.0 mL), 8 h. *Reacted for 16 h.

Inspired by the results presented above, we conducted a series of additional experiments to develop a deeper understanding of the mechanism of the reaction (Scheme 3). To begin with, we conducted a competition experiment between differently substituted N-methoxybenzamides (1h and 1m), and the result indicated that electron-rich substrates were preferentially converted to the corresponding cyanated products, which suggested that the C-H activation process could be occurring via an internal electrophilic substitution (IES)-type mechanism ^{[84, 85, 86, 87, 88]} (Scheme 3(a)). An H/D exchange experiment was then performed in the absence of NCTS (Scheme 3(b)). As shown in Scheme 3(b), a remarkable H/D exchange effect was observed for the recovering substrate [D]_n-1a when D₂O was added to the reaction mixture, which revealed that the step involving the metallation of the C-H bond was largely reversible ^{[89, 90, 91, 92]}. The reaction of the N-methyl-substituted substrate 1r was also investigated to evaluate the role of the N-H bond (Scheme 3(c)). As anticipated, the reaction of 1r and 2 did not proceed, which indicated that the N-H bond was critical to the success of this transformation ^{[93, 94]}. Finally, a kinetic isotope effect (KIE) experiment ^{[93, 94, 95]} was carried out using D-labeled N-methoxybenzamide 1a-d5. As shown in Scheme (3d), the treatment of a 1:1 mixture of 1a and 1a-d5 with NCTS gave a typical KIE value (k_H/k_D = 2.8) for a Rh(III)-catalyzed C−H activation process ^{[96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106]}.

Scheme 3. Mechanistic experiments.

Based on the results presented above and results published elsewhere ^{[47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108]}, we have proposed a preliminary mechanistic pathway for this reaction, which is shown in Scheme 4. Briefly, the initial coordination of N-methoxybenzamide1 to the Rh(III)-catalyst could be the rate-limiting step for the C−H bond cleavage to form the five-membered rhodacycle A. Compound 2 would then coordinate to the Rh(III) center in A, followed by the insertion of the CN moiety into the C−Rh(III) bond to give intermediate B. Finally, the rearrangement of B would lead to the cyanated product 3 and the Rh species C, which would subsequently release the active Rh catalyst for the next catalytic cycle.

Scheme 4. Postulated mechanism.

We have developed for the first time a Rh(III)-catalyzed method for the direct C−H bond cyanation of various N- methoxybenzamides using N-cyano-N-phenyl-p- toluenesulfonamide (NCTS) as an environmentally friendly and versatile cyanating reagent. This new reaction boasts many remarkable features, including mild reaction conditions, moderate to good product yields, good regioselectivity, broad substrate scope and excellent functional group tolerance. Furthermore, the experimental results have provided the basis for a plausible reaction mechanism, as well as deepening our understanding of Rh(III)- catalyzed reactions and extending the concept and scope of the Rh-catalyzed C-H cyanation reactions. Considering the valuable structural features of these products, it is envisioned that these reactions will have broad utility in organic synthesis.