Supporting Information

Supporting Information A General thod for Two-Step Transamidation of Secondary Amides using Commercially Available, Airand Moisture-Stable Palladium/C (-eterocyclic Carbene) Complexes Guangrong ng, Peng Lei,, and Michal Szostak*, Department of Chemistry, Rutgers University, 73 Warren Street, ewark, ew Jersey 07102, United States Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China michal.szostak@rutgers.edu Table of Contents 1 List of Known Compounds/General thods 2 Experimental Procedures and Characterization Data 3 General Procedures 3 Characterization Data of Starting Materials 5 Cross-Coupling of Amides: Variation of Amine 8 Cross-Coupling of Amides: Variation of Amide 12 Control Experiments and Additional Studies 22 References 24 1 and 13 C MR Spectra 25 Corresponding Author: Prof. Dr. M. Szostak Department of Chemistry, Rutgers University 73 Warren Street, ewark, J 07102, United States E-mail: michal.szostak@rutgers.edu SI-1

List of Known Compounds/General thods All starting materials reported in the manuscript have been previously described in literature and prepared by the method reported previously. Amides were prepared by standard methods. 1-3 All experiments were performed using standard Schlenk techniques under nitrogen or argon unless stated otherwise. All solvents were purchased at the highest commercial grade and used as received or after purification by passing through activated alumina columns or distillation from sodium/benzophenone under nitrogen. All solvents were deoxygenated prior to use. All other chemicals were purchased at the highest commercial grade and used as received. Reaction glassware was oven-dried at 140 C for at least 24 h or flame-dried prior to use, allowed to cool under vacuum and purged with argon (three cycles). All products were identified using 1 MR analysis and comparison with authentic samples. GC and/or GC/MS analysis was used for volatile products. All yields refer to yields determined by 1 MR and/or GC or GC/MS using an internal standard (optimization) and isolated yields (preparative runs) unless stated otherwise. 1 MR and 13 C MR spectra were recorded in CDCl 3 on Bruker spectrometers at 500 ( 1 MR) and 125 Mz ( 13 C MR). All shifts are reported in parts per million (ppm) relative to residual CCl 3 peak (7.27 and 77.2 ppm, 1 MR and 13 C MR, respectively). All coupling constants (J) are reported in hertz (z). Abbreviations are: s, singlet; d, doublet; t, triplet; q, quartet; brs, broad singlet. GC-MS chromatography was performed using Agilent P6890 GC System and Agilent 5973A inert XL EI/CI MSD using helium as the carrier gas at a flow rate of 1 ml/min and an initial oven temperature of 50 C. The injector temperature was 250 C. The detector temperature was 250 C. For runs with the initial oven temperature of 50 C, temperature was increased with a 10 C/min ramp after 50 C hold for 3 min to a final temperature of 220 C, then hold at 220 C for 15 min (splitless mode of injection, total run time of 22.0 min). igh-resolution mass spectra (RMS) were measured on a 7T Bruker Daltonics FT-MS instrument. All flash chromatography was performed using silica gel, 60 Å, 300 mesh. TLC analysis was carried out on glass plates coated with silica gel 60 F254, 0.2 mm thickness. The plates were visualized using a 254 nm ultraviolet lamp or aqueous potassium permanganate solutions. 1 MR and 13 C MR data are given for all compounds in the SI for characterization purposes. 1 MR, 13 C MR, MS and RMS data are given for all new compounds. All products have been previously reported, unless stated otherwise. SI-2

Experimental Procedures and Characterization Data General Procedure for the Synthesis of Starting Materials. All amides used in this study have been prepared by methods described by us, 1 Prof. Garg 2 and Prof. Zou. 3 1 MR and 13 C MR data for all amides are given in the section below for characterization purposes. General Procedure for Amide Transamidation. An oven-dried vial equipped with a stir bar was charged with an amide substrate (neat, 1.0 equiv), potassium carbonate (typically, 3.0 equiv), amine (typically, 2.0 equiv), Pd-C catalyst (typically, 3 mol%), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. DME (typically, 0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath and stirred for the indicated time. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with C 2 Cl 2 (10 ml), filtered, and concentrated. The sample was analyzed by 1 MR (CDCl 3, 500 Mz) and GC-MS to obtain conversion, selectivity and yield using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (EtAc/hexanes) afforded the tile product. General Procedure for Synthesis of - Amides from Secondary Amides. An oven-dried round-bottomed flask (100 ml) was charged with a secondary amide substrate (5.0 mmol, 1.0 equiv), DMAP (0.1 equiv) and dichloromethane (typically, 0.20 M). 2 (1.0 equiv) was added in one portion and the reaction mixture was allowed to stir at room temperature for 15 h. After the indicated time, the reaction mixture was quenched by with ac 3 (aq., sat., 10 ml), extracted with EtAc (3 20 ml), washed with 2 (1 x 20 ml), brine (1 x 20 ml). The organic layers were combined, dried, and concentrated. Unless stated otherwise, purification by flash chromatography (EtAc/hexanes) afforded pure product. In our hands, - activation of secondary amides typically proceeds in >80% average yields. A previously published procedure for the synthesis of -Ts amides from secondary amides was followed (typically, >80% yields). 3 - activation of secondary amides is vastly preferred due to operational simplicity; however, activation of the amide bond by -tosylation offers an alterative procedure for challenging crosscouplings. We recommend that both methods are tested to facilitate reaction development. SI-3

Representative Synthetic Procedure at 1.0 mmol Scale.. An oven-dried vial equipped with a stir bar was charged with tert-butyl (4-methylbenzoyl)(phenyl)carbamate (neat, 1.0 mmol, 311 mg, 1.0 equiv), potassium carbonate (3.0 mmol, 415 mg, 3.0 equiv), 2,6-dimethylaniline (2.0 mmol, 242 mg, 2.0 equiv), (IPr)Pd(cinnamyl)Cl (3 mol%, 19.4 mg), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. DME (0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 110 C and stirred for 15 h at 110 C. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with C 2 Cl 2 (10 ml), filtered, and concentrated. The sample was analyzed by 1 MR (CDCl 3, 500 Mz) and GC-MS to obtain conversion, selectivity and yield using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (EtAc/hexanes) afforded the tile product. Yield 92% (219.7 mg). White solid. Characterization data are included in the section below. SI-4

Characterization Data for Starting Materials ote: amide substrates exist as single rotamers around the C amide bond. tert-butyl benzoyl(phenyl)carbamate (1a). White Solid. 1 MR (500 Mz, CDCl 3 ) δ 7.76 (d, J = 7.1 z, 2 ), 7.55 (t, J = 7.4 z, 1 ), 7.49-7.43 (m, 4 ), 7.37 (t, J = 7.4 z, 1 ), 7.30 (d, J = 7.4 z, 2 ), 1.26 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 172.78, 153.30, 139.10, 136.98, 131.72, 129.21, 128.28, 128.14, 127.96, 127.80, 83.50, 27.49. tert-butyl (4-methylbenzoyl)(phenyl)carbamate (1b). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.67 (d, J = 7.9 z, 2 ), 7.44 (t, J = 7.7 z, 2 ), 7.35 (t, J = 7.2 z, 1 ), 7.27 (t, J = 8.0 z, 4 ), 2.44 (s, 3 ), 1.29 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 172.58, 152.85, 138.55, 137.86, 135.69, 130.73, 129.92, 129.22, 128.07, 127.98, 126.39, 125.53, 83.57, 27.34, 19.52. tert-butyl (2-methylbenzoyl)(phenyl)carbamate (1c). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.48 (q, J = 7.2 z, 3 ), 7.40 (d, J = 6.9 z, 1 ), 7.38-7.34 (m, 1 ), 7.32 (d, J = 7.9 z, 2 ), 7.27 (d, J = 7.4 z, 2 ), 2.52 (s, 3 ), 1.19 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 172.58, 152.85, 138.55, 137.86, 135.69, 130.73, 129.92, 129.22, 128.07, 127.98, 126.39, 125.53, 83.57, 27.34, 19.52. F 3 C tert-butyl phenyl(4-(trifluoromethyl)benzoyl)carbamate (1d). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.84 (d, J = 8.0 z, 2 ), 7.74 (d, J = 8.2 z, 2 ), 7.47 (t, J = 7.6 z, 2 ), 7.40 (t, J = 7.4 z, 1 ), 7.29 (d, J = 7.2 z, 2 ), 1.27 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 171.38, 152.87, 140.33, 138.52, 133.07 (J 2 = 65.0 z), 129.31, 128.16, 127.98, 125.31 (J 3 = 7.5 z), 123.64 (J 1 = 270.0 z), 84.12, 27.49. 19 F MR (471 Mz, CDCl 3 ) δ -62.93. tert-butyl (4-methoxybenzoyl)(phenyl)carbamate (1e). il. 1 MR (500 Mz, CDCl 3 ) δ 7.77 (d, J = 7.6 z, 2 ), 7.43 (t, J = 7.2 z, 2 ), 7.33 (t, J = 7.3 z, 1 ), 7.28 (d, J = 7.9 z, 2 ), 6.95 (d, J = 7.7 z, 2 SI-5

), 3.88 (s, 3 ), 1.32 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 172.07, 162.78, 153.53, 139.48, 130.86, 129.12, 128.72, 127.75, 127.48, 113.56, 83.10, 55.49, 27.65. F F tert-butyl phenyl(3,4-difluorobenzoyl)carbamate (1f). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.61-7.56 (t, J = 7.3 z, 1 ), 7.52 (brs, 1 ), 7.45 (t, J = 7.4 z, 2 ), 7.38 (t, J = 7.2 z, 1 ), 7.25 (d, J = 7.9 z, 3 ), 1.33 (s, 9 ). 13 C MR (125 Mz CDCl 3 ) δ 170.31, 152.56 (J 1 = 253.8 z), 153.00, 150.07 (J 1 = 250.0 z), 138.70, 133.51 (J 3 = 5.0 z), 129.28, 128.05, 127.84, 124.92 (J 2 = 15.0 z, J 3 = 7.5 z), 117.81 (J 2 = 18.8 z), 117.26 (J 1 = 17.5 z), 83.98, 27.60. 19 F MR (471 Mz, CDCl 3 ) δ - 131.63, -136.54. tert-butyl phenyl((4-(methoxycarbonyl)benzoyl)carbamate (1g). White solid. 1 MR (500 Mz, CDCl 3 ) δ 8.14 (d, J = 8.1 z, 2 ), 7.78 (d, J = 8.1 z, 2 ), 7.46 (t, J = 7.6 z, 2 ), 7.38 (t, J = 7.3 z, 1 ), 7.28 (d, J = 7.8 z, 2 ), 3.97 (s, 3 ), 1.26 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 171.83, 166.21, 152.93, 141.01, 138.62, 132.53, 129.52, 129.27, 128.07, 127.99, 127.78, 84.01, 52.42, 27.51. tert-butyl (furan-2-carbonyl)(phenyl)carbamate (1h). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.57-7.54 (m, 1 ), 7.43 (t, J = 7.6 z, 2 ), 7.35 (t, J = 7.4 z, 1 ), 7.28 (d, J = 7.2 z, 2 ), 7.04 (d, J = 3.5 z, 1 ), 6.53 (dd, J = 3.5, 1.7 z, 1 ), 1.42 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 161.23, 152.84, 148.49, 145.05, 138.64, 129.16, 127.96, 127.88, 118.13, 112.29, 83.34, 77.31, 77.05, 76.80, 27.70. Ts -thyl--tosylbenzamide (1i). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.85 (d, J = 8.0 z, 2 ), 7.57 (d, J = 8.2 z, 2 ), 7.53 (t, J = 8.0 z, 1 ), 7.43 (t, J = 7.6 z, 2 ), 7.35 (d, J = 8.1 z, 2 ), 3.30 (s, 3), 2.47 (s, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 171.48, 144.91, 135.21, 134.52, 131.96, 129.62, 128.49, 128.42, 128.29, 35.60, 21.68. SI-6

Ts -enyl--tosylbenzamide (1j). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.86 (d, J = 8.3 z, 2 ), 7.46 (d, J = 8.3 z, 2 ), 7.34 (d, J = 8.1 z, 2 ), 7.29 (m, 4 ), 7.21-7.16 (m, 4 ), 2.47 (s, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 169.90, 144.81, 137.43, 135.25, 133.67, 131.74, 130.40, 129.49, 129.25, 129.10, 129.03, 128.60, 127.98, 21.73. tert-butyl benzoyl(methyl)carbamate (1k). il. 1 MR (500 Mz, CDCl 3 ) δ 7.53 (d, J = 7.2 z, 2 ), 7.48 (t, J = 7.4 z, 1 ), 7.40 (t, J = 7.5 z, 2 ), 3.33 (s, 3 ), 1.17 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 173.59, 153.54, 137.91, 130.85, 127.99, 127.41, 82.98, 32.55, 27.37. Bn tert-butyl benzoyl(benzyl)carbamate (1l). il. 1 MR (500 Mz, CDCl 3 ) δ 7.54 (d, J = 7.0 z, 2 ), 7.47 (dd, J = 10.9, 7.4 z, 3 ), 7.41 (d, J = 7.7 z, 2 ), 7.37 (s, 2 ), 7.30 (s, 1 ), 5.02 (s, 2 ), 1.15 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 173.09, 153.46, 137.86, 137.73, 131.04, 128.45, 128.16, 128.06, 127.46, 127.40, 83.18, 48.88, 27.35. C 9 19 tert-butyl (1-decanoyl)(phenyl)carbamate (1m). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.41 (t, J = 7.2 z, 2 ), 7.34 (t, J = 7.3 z, 1 ), 7.09 (d, J = 7.7 z, 2 ), 2.92 (t, J = 7.4 z, 2 ), 1.70 (p, J = 7.3, 6.8 z, 2 ), 1.40 (s, 9 ), 1.29 (s, 12 ), 0.90 (t, J = 6.4 z, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 175.97, 152.75, 139.17, 128.90, 128.22, 127.66, 82.93, 38.03, 31.90, 29.48, 29.30, 29.23, 27.84, 25.01, 22.69, 14.13. SI-7

Transamidation of Amides: Variation of Amine ucleophile 2,6-Dimethylaniline (2a) (Scheme 1, Entry 1) 2 eolyst CX31, K 2 C 3 1a 2a 3a According to the general procedure, the reaction of tert-butyl benzoyl(phenyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 [(IPr)Pd(cinnamyl)Cl] (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 98% yield (44.2 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.94 (m, 2 ), 7.59 (m, 1 ), 7.51 (m, 3 ), 7.15 (m, 3 ), 2.30 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.99, 135.61, 134.47, 133.87, 131.82, 128.77, 128.29, 127.47, 127.23, 18.49. Aniline (2b) (Scheme 1, Entry 2) 2 eolyst CX31, K 2 C 3 1b 2b 3b According to the general procedure, the reaction of tert-butyl (4- methylbenzoyl)(phenyl)carbamate (0.20 mmol), aniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 98% yield (41.5 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 8.01 (s, 1 ), 7.78 (m, 2 ), 7.67 (m, 2), 7.37 (m, 2 ), 7.27 (m, 2 ), 7.16 (m, 1 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.81, 142.31, 138.10, 132.12, 129.39, 129.04, 127.09, 124.41, 120.27, 21.51. p-anisidine (2c) (Scheme 1, Entry 3) SI-8

2 eolyst CX31, K 2 C 3 1a 2c 3c According to the general procedure, the reaction of tert-butyl benzoyl(phenyl)carbamate (0.20 mmol), p-anisidine (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 86% yield (39.0 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.88 (m, 3 ), 7.55 (m, 3 ), 7.48 (m, 2 ), 6.92 (m, 2 ), 3.83 (s, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.67, 156.63, 135.03, 131.69, 131.01, 128.73, 127.00, 122.14, 114.23, 55.51. p-(trifluoromethyl)aniline (2d) (Scheme 1, Entry 4) 2 eolyst CX31, K 2 C 3 CF 3 CF 3 1a 2d 3d According to the general procedure, the reaction of tert-butyl benzoyl(phenyl)carbamate (0.20 mmol), p-(trifluoromethyl)aniline (3.0 equiv), K 2 C 3 (4.5 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 76% yield (40.2 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 8.00 (s, 1 ), 7.90 (m, 2 ), 7.81 (m, 2 ), 7.65 (m, 2 ), 7.61 (m, 1 ), 7.54 (m, 2 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.83, 140.98, 134.41, 132.31, 130.58, 128.96, 127.06, 126.40 (J 3 = 7.5 z), 124.06 (J 1 = 270.0 z), 119.71. 19 F MR (471 Mz, CDCl 3 ) δ -62.44. 2,6-Diisopropylaniline (2e) (Scheme 1, Entry 5) SI-9

2 eolyst CX31, K 2 C 3 1a 2e 3e According to the general procedure, the reaction of tert-butyl benzoyl(phenyl)carbamate (0.20 mmol), 2,6-diisopropylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 79% yield (44.3 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.95 (m, 2 ), 7.60 (m, 1 ), 7.53 (m, 2 ), 7.38 (m, 2 ), 7.25 (m, 2 ), 3.17 (p, J = 6.8 z, 2 ), 1.25 (d, J = 6.7 z, 12 ). 13 C MR (125 Mz, CDCl 3 ) δ 166.94, 146.39, 134.63, 131.78, 131.15, 128.83, 128.51, 127.19, 123.58, 28.93, 23.67. -thylaniline (2f) (Scheme 1, Entry 6) eolyst CX31, K 2 C 3 1a 2f 3f According to the general procedure, the reaction of tert-butyl benzoyl(phenyl)carbamate (0.20 mmol), -methylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 77% yield (32.6 mg). il. 1 MR (500 Mz, CDCl 3 ) δ 7.32 (m, 2 ), 7.27-7.21 (m, 3 ), 7.20-7.14 (m, 3 ), 7.06 (m, 2 ), 3.52 (s, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 170.68, 144.93, 135.94, 129.58, 129.14, 128.72, 127.72, 126.91, 126.48, 38.41. tert-butylamine (2g) (Scheme 1, Entry 7) 2 eolyst CX31, K 2 C 3 1a 2g 3g SI-10

According to the general procedure, the reaction of tert-butyl benzoyl(phenyl)carbamate (0.20 mmol), tert-butylamine (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 80% yield (28.4 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.74 (m, 2 ), 7.49 (m, 1 ), 7.43 (m, 2 ), 5.97 (s, 1 ), 1.50 (s, 9 ). 13 C MR (125 Mz, CDCl 3 ) δ 166.89, 135.94, 131.07, 128.47, 126.69, 51.60, 28.89. 2-Aminobiphenyl (2h) (Scheme 1, Entry 8) eolyst CX31, K 2 C 3 2 1a 2h 3h According to the general procedure, the reaction of tert-butyl benzoyl(phenyl)carbamate (0.20 mmol), 2-aminobiphenyl (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 84% yield (46.0 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 8.57 (m, 1 ), 8.03 (s, 1 ), 7.63 (m, 2 ), 7.56-7.52 (m, 2 ), 7.48 (m, 5 ), 7.41 (m, 2 ), 7.33 (m, 1 ), 7.25 (m, 1 ). 13 C MR (125 Mz, CDCl 3 ) δ 164.96, 138.07, 134.94, 134.80, 132.32, 131.73, 130.00, 129.37, 129.24, 128.75, 128.62, 128.20, 126.81, 124.36, 121.12. 3-amino-9-ethylcarbazole (2i) (Scheme 1, Entry 9) 2 eolyst CX31, K 2 C 3 Et 1a 2i 3i Et According to the general procedure, the reaction of tert-butyl benzoyl(phenyl)carbamate (0.20 mmol), 3-amino-9-ethylcarbazole (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 75% yield (47.0 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 8.47 (s, 1 ), 8.12 (m, 1 ), 7.97 (m, 3 ), 7.67 (m, 1 ), 7.62-7.57 (m, 1 ), 7.54 (m, 2 ), 7.53-7.47 (m, 1 SI-11

), 7.46-7.40 (m, 2 ), 7.25 (m, 1 ), 4.40 (q, J = 7.2 z, 2 ), 1.47 (t, J = 7.2 z, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.72, 157.46, 140.50, 137.41, 135.30, 131.65, 129.68, 128.79, 127.00, 125.93, 123.14, 122.78, 120.73, 119.66, 118.82, 113.13, 108.59, 37.66, 13.84. Transamidation of Amides: Variation of Amides tert-butyl (4-methylbenzoyl)(phenyl)carbamate (1b) (Scheme 1, Entry 10) 2 eolyst CX31, K 2 C 3 1b 2a 3j According to the general procedure, the reaction of tert-butyl (4- methylbenzoyl)(phenyl)carbamate (1.0 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 92% yield (219.7 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.85 (m, 2 ), 7.38 (brs, 1 ), 7.32 (m, 2 ), 7.19-7.12 (m, 3 ), 2.46 (s, 3 ), 2.30 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.78, 142.31, 135.57, 133.97, 131.64, 129.42, 128.28, 127.36, 127.23, 21.52, 18.52. tert-butyl (2-methylbenzoyl)(phenyl)carbamate (1c) (Scheme 1, Entry 11) 2 eolyst CX31, K 2 C 3 1c 2a 3k According to the general procedure, the reaction of tert-butyl (2- methylbenzoyl)(phenyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 93% yield (44.4 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.60 (m, 1 ), 7.40 (m, 1 ), 7.34-7.29 (m, 2 ), 7.17 (m, 3 ), 7.04 (s, 1 ), SI-12

2.58 (s, 3 ), 2.37 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 168.42, 136.63, 136.37, 135.54, 133.62, 131.30, 130.21, 128.39, 127.58, 126.67, 125.87, 19.97, 18.71. tert-butyl phenyl(4-(trifluoromethyl)benzoyl)carbamate (1d) (Scheme 1, Entry 12) F 3 C 2 eolyst CX31, K 2 C 3 F 3 C 1d 2a 3l According to the general procedure, the reaction of tert-butyl phenyl(4- (trifluoromethyl)benzoyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 74% yield (43.3 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 8.05 (m, 2 ), 7.78 (m, 2 ), 7.46 (s, 1 ), 7.18 (m, 3 ), 2.31 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 164.62, 137.75, 135.46, 133.38, 128.42, 127.77, 127.68, 125.85(J 3 = 7.5 z), 122.57, 18.48. 19 F MR (471 Mz, CDCl 3 ) δ -62.98. tert-butyl (4-methoxybenzoyl)(phenyl)carbamate (1e) (Scheme 1, Entry 13) 2 eolyst CX31, K 2 C 3 1e 2a 3m According to the general procedure, the reaction of tert-butyl (4- methoxylbenzoyl)(phenyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 88% yield (45.0 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.92 (m, 2 ), 7.31 (s, 1 ), 7.15 (m, 3 ), 7.02 (m, 2 ), 3.91 (s, 3 ), 2.31 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.33, 162.47, 135.55, 134.04, 129.06, 128.28, 127.31, 126.73, 113.96, 55.50, 18.54. tert-butyl (3,4-difluorobenzoyl)(phenyl)carbamate (1f) (Scheme 1, Entry 14) SI-13

F F 2 eolyst CX31, K 2 C 3 1f 2a 3n F F According to the general procedure, the reaction of tert-butyl (3,4- difluorobenzoyl)(phenyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 95% yield (49.7 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.78 (m, 1 ), 7.66 (m, 1 ), 7.45 (s, 1 ), 7.26 (m, 1 ), 7.19-7.11 (m, 3 ), 2.27 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 163.78, 150.39 (J 1 = 288.8 z), 135.45, 133.43, 131.45 (J 3 = 6.3 z), 128.37, 127.70, 123.59 (J 3 = 6.3 z), 117.65 (J 2 = 17.5 z), 117.14 (J 2 = 17.5 z), 99.99, 18.42. 19 F MR (471 Mz, CDCl 3 ) δ -132.06, -135.67. tert-butyl phenyl((4-(methoxycarbonyl)benzoyl)carbamate (1g) (Scheme 1, Entry 15) 2 C 2 eolyst CX31, K 2 C 3 2 C 1g 2a 3o According to the general procedure, the reaction of tert-butyl phenyl((4- (methoxycarbonyl)benzoyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 77% yield (43.5 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 8.17 (m, 2 ), 7.99 (m, 2 ), 7.52 (s, 1 ), 7.17 (m, 3 ), 3.99 (s, 3 ), 2.30 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 166.25, 165.07, 138.39, 135.51, 133.52, 133.00, 130.02, 128.37, 127.68, 127.27, 52.48, 18.50. tert-butyl (furan-2-carbonyl)(phenyl)carbamate (1h) (Scheme 1, Entry 16) SI-14

2 eolyst CX31, K 2 C 3 1h 2a 3p According to the general procedure, the reaction of tert-butyl (furan-2- carbonyl)(phenyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 93% yield (40.1 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.65 (s, 1 ), 7.55 (s, 1 ), 7.25 (m, 1 ), 7.15 (m, 3 ), 6.59 (s, 1 ), 2.31 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 156.44, 147.97, 144.16, 135.75, 132.96, 128.32, 127.54, 115.06, 112.41, 18.60, 18.56. -thyl--tosylbenzamide (1i) (Table 2, Entry 1) Ts 2 eolyst CX31, K 2 C 3 1i 2c 3c According to the general procedure, the reaction of -methyl--tosylbenzamide (0.20 mmol), p- anisidine (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 91% yield (41.3 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.88 (m, 3 ), 7.55 (m, 3 ), 7.48 (m, 2 ), 6.92 (m, 2 ), 3.83 (s, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.67, 156.63, 135.03, 131.69, 131.01, 128.73, 127.00, 122.14, 114.23, 55.51. -thyl--tosylbenzamide (1i) (Table 2, Entry 2) Ts 2 eolyst CX31, K 2 C 3 1i 2a 3a SI-15

According to the general procedure, the reaction of -methyl--tosylbenzamide (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 83% yield (37.3 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.94 (m, 2 ), 7.59 (m, 1 ), 7.51 (m, 3 ), 7.15 (m, 3 ), 2.30 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.99, 135.61, 134.47, 133.87, 131.82, 128.77, 128.29, 127.47, 127.23, 18.49. -enyl--tosylbenzamide (1j) (Table 2, Entry 3) Ts 2 eolyst CX31, K 2 C 3 1j 2a 3a According to the general procedure, the reaction of -phenyl--tosylbenzamide (0.20 mmol), 2,6-dimethylaniline (3.0 equiv), K 2 C 3 (4.5 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 72% yield (32.5 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.94 (m, 2 ), 7.59 (m, 1 ), 7.51 (m, 3 ), 7.15 (m, 3 ), 2.30 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.99, 135.61, 134.47, 133.87, 131.82, 128.77, 128.29, 127.47, 127.23, 18.49. tert-butyl benzoyl(methyl)carbamate (1k) (Table 2, Entry 4) 2 eolyst CX31, K 2 C 3 1k 2c 3c According to the general procedure, the reaction of tert-butyl benzoyl(methyl)carbamate (0.20 mmol), p-anisidine (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 96% yield (43.5 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.88 (m, 3 ), 7.55 (m, 3 ), 7.48 (m, 2 ), 6.92 (m, 2 ), 3.83 (s, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.67, 156.63, 135.03, 131.69, 131.01, 128.73, 127.00, 122.14, 114.23, 55.51. SI-16

tert-butyl benzoyl(benzyl)carbamate (1l) (Table 2, Entry 5) Bn 2 eolyst CX31, K 2 C 3 1l 2c 3c According to the general procedure, the reaction of tert-butyl benzoyl(benzyl)carbamate (0.20 mmol), p-anisidine (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 77% yield (34.9 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.88 (m, 3 ), 7.55 (m, 3 ), 7.48 (m, 2 ), 6.92 (m, 2 ), 3.83 (s, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.67, 156.63, 135.03, 131.69, 131.01, 128.73, 127.00, 122.14, 114.23, 55.51. tert-butyl benzoyl(benzyl)carbamate (1l) (Table 2, Entry 6) Bn 2 eolyst CX31, K 2 C 3 1l 2a 3a According to the general procedure, the reaction of tert-butyl benzoyl(benzyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%) in DME (0.25 M) for 15 h at 110 C, afforded after filtration and chromatography the title compound in 71% yield (31.9 mg). White solid. 1 MR (500 Mz, CDCl 3 ) δ 7.94 (m, 2 ), 7.59 (m, 1 ), 7.51 (m, 3 ), 7.15 (m, 3 ), 2.30 (s, 6 ). 13 C MR (125 Mz, CDCl 3 ) δ 165.99, 135.61, 134.47, 133.87, 131.82, 128.77, 128.29, 127.47, 127.23, 18.49. SI-17

Control Experiments General Procedure. An oven-dried vial equipped with a stir bar was charged with an amide substrate (neat, 1.0 equiv), potassium carbonate (3 equiv) and amine (2.0 equiv), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. DME (0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 110 C and stirred at 110 C for the indicated time. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with C 2 Cl 2 (10 ml), filtered, and concentrated. The sample was analyzed by 1 MR (CDCl 3, 500 Mz) and/or GC-MS to obtain conversion, selectivity and yield using internal standard and comparison with authentic samples. Scheme S1. Determination of on-catalyzed (tal-free) Addition to -Activated Secondary Amides in the Absence of (IPr)Pd(cinnamyl)Cl. Z R' R 1 K 2 C 3 R 2 R 2 R 1 morpholine 2,6- dimethylaniline p-anisidine tert-butylamine Ts Ts n.r. = no reaction. 94% n.r. n.r. <10% n.r. n.r. n.r. n.r. 98% n.r. 67% 46% 61% n.r. n.r. 18% SI-18

Additional Discussion. The obtained results (Scheme SI1) are consistent with the facility of nucleophilic addition to the resonance destabilized amide bond (ER, resonance energy, = 7-9 kcal/mol) 4 in that simple primary and secondary amines undergo addition to -Ts and activated - amides. ote that - amides are unreactive towards anilines, including stericallyhindered and nucleophilic anilines, and towards α-branched primary amines. Additionally, we have surveyed the facility of non-catalyzed (metal-free) addition to - and -Ts amines under nucleophilic catalysis conditions (amine, Et 3, DMAP, TF, 60 to 110 C) (not shown). Under these conditions, we found that -Ts and - amides are unreactive towards nucleophilic aniline substrates, such as p-anisidine. Moreover, - amides are unreactive towards α-branched primary amines. Thus, the borderline of metal-free (non-catalyzed) nucleophilic addition can be located around the -aryl/ts amide bond activation geometry for the addition of nucleophilic aniline substrates and α-branched primary amines. ote that sterically-hindered anilines are unreactive throughout the amide bond -activation geometries, while the addition of α-branched primary amines can be effected under nucleophilic catalysis conditions only to -aryl/ts amides. Thus, Pd-C catalysis enables transamidation with non-nucleophilic aromatic and α-branched amines in the absence of strong bases, furnishing secondary and tertiary transamidation products that are particularly appealing from the synthetic point of view. SI-19

ne-pot -Activation/Transamidation General Procedure. An oven-dried vial equipped with a stir bar was charged with - phenylbenzamide (neat, 0.2 mmol, 1.0 equiv), di-tert-butyl-dicarbonate (1.0 equiv), and DMAP (10 mol%). DCM (0.13 M) was added with vigorous stirring and the resulting reaction mixture was stirred at room temperature for 15 h. After indicated time, the solvent was removed under high vacuum, and the same reaction vial was charged with 2,6-dimethylaniline (2.0 equiv), potassium carbonate (3 equiv) and eolyst CX31 (3 mol%), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. DME (0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 110 C and stirred at 110 C for 15 h. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with C 2 Cl 2 (10 ml), filtered, and concentrated. The sample was analyzed by 1 MR (CDCl 3, 500 Mz) and/or GC-MS to obtain conversion, selectivity and yield using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (EtAc/hexanes) afforded the tile product. Yield 85% (38.3 mg). White solid. Characterization data matched those described above. Scheme S2. ne-pot -Activation/Transamidation using (IPr)Pd(cinnamyl)Cl. 2 1. 2 2. eolyst CX31, K 2 C 3 1a' 2a 3a SI-20

Transamidation of α-alkyl Amides General Procedure. An oven-dried vial equipped with a stir bar was charged with tert-butyl (1- decanoyl)(phenyl)carbamate (0.20 mmol), 2,6-dimethylaniline (2.0 equiv), K 2 C 3 (3.0 equiv) and eolyst CX31 (3 mol%), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. DME (0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 110 C and stirred for 15 h at 110 C. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with C 2 Cl 2 (10 ml), filtered, and concentrated. The sample was analyzed by 1 MR (CDCl 3, 500 Mz) and GC-MS to obtain conversion, selectivity and yield using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (EtAc/hexanes) afforded the tile product. Yield 74% (40.6 mg). White solid. tert- Butyl (1-decanoyl)(phenyl)carbamate (3q): 1 MR (500 Mz, CDCl 3 ) δ 7.09 (m, 3 ), 6.85 (s, 1 ), 2.41 (t, J = 7.6 z, 2 ), 2.23 (s, 6 ), 1.76 (q, J = 7.5 z, 2 ), 1.40 (d, J = 7.0 z, 2 ), 1.33 (m, 10 ), 0.91 (t, J = 6.6 z, 3 ). 13 C MR (125 Mz, CDCl 3 ) δ 171.72, 135.50, 133.91, 128.16, 127.29, 36.85, 31.88, 29.50, 29.44, 29.39, 29.29, 26.13, 22.69, 18.46, 14.12. Scheme S3. Transamidation of α-alkyl Amide Catalyzed by (IPr)Pd(cinnamyl)Cl. C 9 19 2 eolyst CX31, K 2 C 3 C 9 19 1m 2a 3q SI-21

Amide Exchange Reactions General Procedure. An oven-dried vial equipped with a stir bar was charged with secondary amine (neat, 1.0 equiv), di-tert-butyl-dicarbonate (1.0 equiv), DMAP (10 mol%) and triethylamine (1.0 equiv). DCM (0.13 M) was added with vigorous stirring and the resulting reaction mixture was stirred at room temperature for 15 h. After indicated time, the solvent was removed under high vacuum, and the same reaction vial was charged with amine (3.0 equiv), potassium carbonate (4.5 equiv) and eolyst CX31 (3 mol%), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. DME (0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 110 C and stirred at 110 C for 15 h. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with C 2 Cl 2 (10 ml), filtered, and concentrated. The sample was analyzed by 1 MR (CDCl 3, 500 Mz) and/or GC-MS to obtain conversion, selectivity and yield using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (EtAc/hexanes) afforded the tile products. Yield (3d) 69%. White solid. Yield (3c) 75%. White solid. Characterization data matched those described above. Scheme S4. Amide Exchange Reactions Catalyzed by (IPr)Pd(cinnamyl)Cl. 2 1. 2 2. eolyst CX31, K 2 C 3 CF 3 CF 3 1e' 2d 3d CF 3 2 1. 2 2. eolyst CX31, K 2 C 3 1d' 2c 3c SI-22

Determination of the Turnover umber General Procedure. An oven-dried vial equipped with a stir bar was charged with tert-butyl benzoyl(phenyl)carbamate (neat, 1.0 equiv), potassium carbonate (4.5 equiv), 2,6- dimethylaniline (3.0 equiv) and eolyst CX31 (0.1 mol%), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. DME (0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 110 C and stirred at 110 C for 15 h. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with C 2 Cl 2 (10 ml), filtered, and concentrated. The sample was analyzed by 1 MR (CDCl 3, 500 Mz) and/or GC-MS to obtain conversion, selectivity and yield using internal standard and comparison with authentic samples. Scheme S5. Determination of Turnover umber in the Suzuki-Miyaura Cross-Coupling of Amide 1a with 2,6-Dimethylaniline using (IPr)Pd(cinnamyl)Cl. 2 eolyst CX31, K 2 C 3 1a 2a 3a Turnover number (T) = 850. Further studies on the development of reaction conditions for C (acyl) amination and improved catalytic systems are underway in our laboratory. SI-23

References 1. a) ng, G.; Szostak, M. Angew. Chem. Int. Ed. 2015, 54, 14518. b) ng, G.; Szostak, M. rg. Lett. 2016, 18, 796. c) Shi, S.; ng, G.; Szostak, M. Angew. Chem. Int. Ed. 2016, 55, 6959. 2. a) Weires,. A.; Baker, E. L.; Garg,. K. at. Chem. 2016, 8, 75. b) Baker, E. L.; Yamano, M. M.; Zhou, Y.; Anthony, S. M.; Garg,. K. at. Commun. 2016, 7, 11554, 1. c) Simmons, B. J.; Weires,. A.; Dander, J. E.; Garg,. K. ACS Catal. 2016, 6, 3176. 3. Li, X.; Zou, G. Chem. Commun. 2015, 51, 5089. 4. Szostak, R.; Shi, S.; ng, G.; Lalancette, R.; Szostak, M. J. rg. Chem. 2016, 81, 8091. SI-24

3a SI-25

3b SI-26

3c SI-27

CF 3 3d SI-28

CF 3 3d SI-29

3e SI-30

3f SI-31

3g SI-32

3h SI-33

3i SI-34

3j SI-35

3k SI-36

F 3 C 3l SI-37

F 3 C 3l SI-38

3m SI-39

F F 3n SI-40

F F 3n SI-41

C 3o SI-42

3p SI-43

C 9 19 3q SI-44