Supporting Information

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1 Supporting Information Palladium-Catalyzed C(sp 3 )-C(sp 2 ) Cross-Coupling of (trimethylsilyl)methyllithium with (hetero)aryl Halides Dorus Heijnen, Valentin Hornillos, Brian P. Corbet, Massimo Giannerini and Ben L. Feringa* Correspondence to: b.l.feringa@rug.nl Stratingh Institute for Organic Chemistry. Nijenborgh 4, Groningen, 9747 AG Groningen The Netherlands S1

2 Table of Contents General Methods General procedure for cross coupling of TMSCH 2 Li with aryl halides Data of Compounds 2a-n,6a-k, 8 S2 S3 S3 S4 1 H and 13 C NMR spectra of isolated compounds S10 S2

3 General methods: Chromatography: Grace Reveleris X2 flash chromatography system used with Grace Flash Cartridges, TLC: Merck silica gel 60, 0.25 mm. Components were visualized by UV and cerium/molybdenum or potassium permanganate staining. Progress, conversion and masses of the products in the reaction were determined by GC-MS (GC, HP6890: MS HP5973) with an HP1 or HP5 column (Agilent Technologies, Palo Alto, CA). 1 H- and 13 C-NMR were recorded on a Varian AMX400 (400 and MHz, respectively) using CDCl 3 as solvent. Chemical shift values are reported in ppm with the solvent resonance as the internal standard (CHCl 3 : 7.26 for 1 H, 77.0 for 13 C). Data are reported as follows: chemical shifts, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br = broad, m = multiplet), coupling constants (Hz), and integration. Melting points were measured using a Büchi Melting Point B-545. All reactions were carried out under a nitrogen atmosphere using oven dried glassware and using standard Schlenk techniques. THF, Et 2 O and toluene were dried and distilled over sodium. Pd-PEPPSI-Ipent was purchased from Aldrich and used without further purification. TMSCH 2 Li (1.0 M in pentane) and all the bromides and chlorides were commercially available and were purchased from Aldrich and TCI Europe. General procedure for cross coupling of TMSCH 2 Li with aryl halides. The corresponding halide (0,6 mmol) and Pd-PEPPSI-IPent complex (5 mol %) were dissolved in toluene (4 ml) in a dried Schlenk flask under inert atmosphere, and the mixture stirred for 5 min. Subsequently, a solution of TMSCH 2 Li (0,72 mmol, 1,2 eq.) diluted to 2 ml (to reach a final concentration of 0,36 M) with toluene was added over 1 h. by the use of a syringe pump. After complete addition, MeOH (1ml) was added to quench the remaining TMSCH 2 Li. The reaction mixture was transferred to a round-bottom flask, Celite was added, and the solvents evaporated in vacuo. The remaining solid was directly loaded on a silica gel column. S3

4 Data of Compounds 2a-n,6a-k, 8 (4-Methoxybenzyl)trimethylsilane (2a): 1 Synthesized according to general method. The product was obtained after column chromatography as a yellow oil (SiO 2, n-pentane). [99 mg, 85% yield]. 1 H- NMR (400MHz, Chloroform-d) δ 6.93 (d, J = 8.69 Hz, 2H), 6.79 (d, J = 8.66 Hz, 2H), 3.78 (s, 3H), 2.02 (s, 2H), 0.01 (s, 9H) 13 C-NMR (100MHz, Chloroform-d) δ 156.5, 132.3, 128.8, 113.6, 55.2, 25.7, 1.9. EI-MS m/z: 194, 179(100%), 121, 73. (3-Methoxybenzyl)trimethylsilane (2b): 2 Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [107 mg, 92% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.15 (t, J = 7.88 Hz, 1H), (m, 3H), 3.80 (s, 3H), 2.09 (s, 2H), 0.02 (s, 9H) 13 C-NMR (100MHz, Chloroform-d) δ 160.0, 142.3, 129.1, 120.8, 113.9, 109.2, 55.1, 27.3, EI-MS m/z: 194, 179, 73(100%). (4-Butylbenzyl)trimethylsilane (2c): Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid (SiO 2, n-pentane). [115 mg, 87% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.08 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 2.60 (t, 2H), 2.09 (s, 2H), 1.63 (p, J = 7.5 Hz, 2H), 1.40 (dq, J = 14.6, 7.3 Hz, 2H), 0.98 (t, J = 7.3 Hz, 3H), 0.04 (s, 9H). 13 C-NMR (100 MHz, Chloroform-d) δ 138.2, 137.4, 128.2, 127.9, 35.2, 33.8, 26.5, 22.5, 14.0, EI-MS m/z: 220, 73 (100%). (2,4-Dimethylbenzyl)trimethylsilane (2d): Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [90 mg, 78% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 6.96 (s, 1H), (m, 2H), 2.29 (s, 3H), 2.22 (s, 3H), 2.08 (s, 2H), 0.03 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 135.8, 134.5, 133.4, 131.0, 128.8, 126.4, 26.3, 21.0, 20.4, EI-MS m/z: 192, 177, 161, 73(100%). N,N-Dimethyl-3-((trimethylsilyl)methyl)aniline (2e): Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [107 mg, 86% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.11 (t, J = 8.04 Hz, 1H), 6.52 (m, 1H), 6.42 (m, 2H), 2.94 (s, 6H), 2.07 (s, 2H), 0.03 (s, 9H) 13 C-NMR (100MHz, Chloroform-d) δ 150.6, 141.2, 128.7, 117.1, 112.8, 108.7, 40.8, 27.4, EI-MS m/z: 207(100%), 192, 135, 133, 73 1 Giannerini, M.; Fañanás, M. F.; Feringa, B.L. Nature Chem., 2013, 5, Das, M.; O'Shea, D. Tetrahedron, 2013, 96, S4

5 4-(4-((Trimethylsilyl)methyl)phenyl)morpholine (2f): Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [102 mg, 68% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 6.92 (d, J = 8.26 Hz, 2H), 6.81 (d, J = 8.26 Hz, 2H), 3.86 (t, J = 4.71 Hz, 4H), 3.10 (t, J = 4.86 Hz, 4H), 2.00 (s, 2H), 0.02 (s, 9H) 13 C-NMR (100MHz, Chloroform-d 3) δ 148.0, 132.2, 128.7, 116.0, 67.0, 50.0, 25.7, EI-MS m/z: 249(100%), 176, 73. (4-((Trimethylsilyl)methyl)phenyl)methanol (2g): 3 Synthesized according to general method with the slow addition of 1.0 eq. of isopropylmagnesiumchloride (2.0 M in THF) prior to the addition of the catalyst. The product was obtained after column chromatography as a brown oil (SiO 2, n-pentane). [75 mg, 65% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.18 (d, J = 7.9 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 4.58 (d, J = 4.6 Hz, 2H), 2.06 (s, 2H), 1.91 (s, 1H), (s, 9H). 13 C-NMR (101 MHz, Chloroform-d) δ 140.0, 136.3, 128.2, , 65.3, 26.8, EI-MS m/z: 194, 179, 104 (100%), ((Trimethylsilyl)methyl)-1H-indole (2h): Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [84 mg, 69% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.97 (s, 1H), 7.51 (d, J = 8.1Hz, 1H), (m, 1H), 7.02 (s, 1H), (m, 1H), (m, 1H), 2.20 (s, 2H), 0.03 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 136.6, 134.6, 124.8, 123.0, 121.4, 120.2, 109.8, 102.4, 27.2, EI-MS m/z: 203, 130, 73(100%). Trimethyl(naphtalen-2-ylmethyl)silane (2i): 4 Synthesized according to general method. The product was obtained after column chromatography as a white solid (SiO 2, n-pentane). [110 mg, 89% yield]. 1 H-NMR: (400MHz, Chloroform-d) δ (m, 3H), (m, 3H), 7.20 (dd, J = 8.32, 1.69 Hz, 1H), 2.29 (s, 2H), 0.06 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 138.2, 133.8, 131.0, 127.9, 124,5, 127.5, 127.0, 125.7, 125.1, 124.4, 27.3, EI-MS m/z: 214, 141, 73(100%). Trimethyl(naphthalen-1-ylmethyl)silane (2j): 5 Synthesized according to general method. The product was obtained after column chromatography as a colorless oil. (SiO 2, n-pentane). [116 mg, 90% yield]. 1 H-NMR (400 MHz, Chloroform-d) δ 7.96 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 7.4 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.47 (dd, J = 6.8, 2.9 Hz, 2H), 7.37 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 7.1 Hz, 1H), 2.59 (s, 2H), 0.01 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 137.2, 133.9, 131.7, 128.6, 125.5, 125.3, 125.2, 124.9, 124.8, 124.6, 23.4, EI-MS m/z: 214, 141, 73(100%). 3 Trahanovsky, W.S.; Lorimor, S. P. J. Org. Chem. 2006, 71, Huckins, J.R.; Rychnovsky S.D. J. Org. Chem. 2003, 68, Molander, G.A.; Yun, C.; Ribagorda, M.; Biolatto, B. J. Org. Chem. 2003, 68, S5

6 Trimethyl(4-(trifluoromethyl)benzyl)silane (2k): 6 Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [100 mg, 72% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.48 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 2.17 (s, 2H), 0.02 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 145.1, 145.1, 128.0, 126.4, 126.1, 125.9, 125.0(q, J = 3.8 Hz), 123.2, 27.4, F-NMR (376-MHz, Chloroform-d) δ EI-MS m/z: 232, 217, 140 (100%), 73. (4-Fluoro-3-methylbenzyl)trimethylsilane (2l): Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [103 mg, 88% yield]. 1 H-NMR (400MHz, Chloroform-d) δ (m, 3H), 2.26 (s, 3H), 2.03 (s, 2H), 0.02 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 160.0, 157.6, 135.6, 130.7, 130.7, 129.0, 128.2, 126.4, 124.2,124.0, 114.6, 114.3, 25.9, 14.6, F-NMR (376MHz, Chloroform-d) δ EI-MS m/z: 196, 181, 104 (100%), 73. ((2,5-Dimethyl-1,4-phenylene(bis(methylene))bis(trimethylsilane) (2n): 7 Synthesized according to general method with the addition of 2.4 eq. of Li-CH 2 TMS. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [147 mg, 88% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 6.73 (s, 2H), 2.17 (s, 6H), 2.03 (s, 4H), 0.02 (s, 18H). 13 C-NMR (100MHz, Chloroform-d) δ 134.1, 131.5, 130.5, 22.8, 19.9, EI-MS m/z: 278(100%), 190, 175, 73. TMS N 3-((Trimethylsilyl)methyl)pyridine (2m): 8 Synthesized according to general method. The product was obtained after column chromatography as a yellow oil (SiO 2, n-pentane). [Full conversion, 30 mg, 31% yield]. 1 H-NMR (400 MHz, Chloroform-d) δ 8.31 (dd, J = 4.8, 1.5 Hz, 1H), 8.27 (d, J = 1.9 Hz, 1H), (m, 1H), 7.12 (dd, J = 7.8, 4.8 Hz, 1H), 2.03 (s, 2H), (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 149.2, 145.4, 136.1, 135.0, 123.0, 23.9, EI-MS m/z: 165, 150, 73(100%). 6 Tobisu, M.; Kita,Y.; Ano, Y.; Chatani, N. J. Am. Chem. Soc., 2008, 130, Bock, H.; Kaim, W.; Chem. Ber. 1978, 111, Wu, Y.; Li, L.; Li, H.; Gao, L.; Xie, H.; Zhang, Z.; Su, Z.; Hu, C.; Song, Z. Org. Lett., 2014, 16, S6

7 (Anthracen-9-ylmethyl)trimethylsilane (6a) 9 : Synthesized according to general method. The product was obtained after column chromatography as a yellow solid (SiO 2, n-pentane). [143 mg, 90% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 8.28 (s, 1H), 8.23 (d, J = 9.4 Hz, 2H), 8.03 (d, J = 9.7 Hz, 2H), (m, 4H), 3.23 (s, 2H), 0.06 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 134.3, 131.7, 129.2, 129.0, 125.5, 124.8, 124.5, 123.7, 19.0, EI-MS m/z: 264(100%), 249, 191, 73. (2-Isopropylbenzyl)trimethylsilane (6b): Synthesized according to general method. The product was obtained after column chromatography as a yellow oil. (SiO 2, n-pentane). [105 mg, 85% yield] 1 H- NMR (400MHz, Chloroform-d) δ 7.27 (dd, J = 7.4, 1.7 Hz, 1H), 7.11 (dtd, J = 14.5, 7.2, 1.7 Hz, 2H), 7.01 (dd, J = 7.4, 1.7 Hz, 1H), 3.10 (hept, J = 6.9 Hz, 1H), 2.21 (s, 2H), 1.27 (dd, J = 6.8, 0.4 Hz, 6H), 0.07 (d, J = 0.5 Hz, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 145.1, 137.2, 129.2, 125.2, 124.9, 124.5, 29.1, 23.5, 23.2, EI-MS m/z: 206, 191, 117, 73(100%). ([1,1'-Biphenyl]-2-ylmethyl)trimethylsilane (6c): 10 Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [133 mg, 92% yield]. 1 H-NMR (400MHz, Chloroform-d) δ (m, 9H), 2.26 (s, 2H), (s, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 142.5, 140.7, 138.2, 130.3, 129.7, 129.2, 128.0, 127.0, 126.6, 124.1, 23.5, EI-MS m/z: 240, 225, 165, 73(100%). Trimethyl(2,4,6-tri-tert-butylbenzyl)silane (6d): Synthesized according to general method. The product was obtained after column chromatography as a yellow oil. (SiO 2, n-pentane). GC/MS analysis showed 8% 2,4,6-tri-tert-butylbenzene. [182 mg, 85% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.25 (d, J = 10.5 Hz, 2H), 7.16 (t, J = 1.8 Hz, 2H), (m, 2H), 1.33 (d, J = 1.9 Hz, 20H), 1.28 (d, J = 1.9 Hz, 7H), (m, 2H), (d, J = 1.9 Hz, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 149.7, 149.3, 120.2, 119.0, 38.9, 38.4, 34.9, 31.6, 28.6, 10.9, EI-MS m/z: 332, 274, 231(100%), 215, Kendall, K.J.; Engler, T.A.; Shechter, H. J. Org. Chem., 1999, 64, Sengupta, S.; Leite, M.; Raslan, D.S.; Quesnelle, C.; Snieckus, V. J. Org. Chem., 1992, 57, S7

8 ((9H-Fluoren-2-yl)methyl)trimethylsilane (6e): Synthesized according to general method. The product was obtained after column chromatography as a pale yellow solid (SiO 2, n-pentane). [145 mg, 96% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.76 (d, J = 7.5 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.55 (d, J = 7.4 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), (m, 1H), 7.23 (s, 1H), 7.06 (d, J = 7.8 Hz, 1H), 3.89 (s, 2H), 2.21 (s, 2H), 0.07 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 143.5, 142.9, 142.0, 139.4, 137.8, (2x), 125.9, 124.9, 124.6, 119.5, 119.3, 36.8, 27.3, EI-MS m/z: 252, 237, 179, 73(100%). Trimethyl(2-(trifluoromethoxy)benzyl)silane (6h): Synthesized according to general method. The product was obtained after column chromatography as a yellow oil. (SiO 2, n-pentane). [80 mg, 54% yield] 1 H-NMR (400 MHz, Chloroform-d) δ (m, 4H), 2.16 (s, 2H), 0.02 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 146.7, 133.2, 130.4, 126.2, 125.2, 121.9, 119.9, 119.4, 20.8, F- NMR (376MHz, Chloroform-d) δ EI-MS m/z: 248, 156, 90, 73(100%). 2,6-Bis((trimethylsilyl)methyl)naphthalene (6k): Synthesized according to general method. The product was obtained after column chromatography as a white solid (SiO 2, n-pentane). [120 mg, 66% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.60 (d, J = 8.3 Hz, 1H), 7.38 (s, 1H), 7.12 (dd, J = 8.3, 1.5 Hz, 1H), 2.23 (s, 2H), 0.04 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 136.5, 131.4, 127.8, 126.6, 124.9, 27.1, EI-MS m/z: 300, 299, 212, 197, 73 (100%). 1,3,5-Tris((trimethylsilyl)methyl)benzene (6j): 11 Synthesized according to general method with the addition of 3.6 equiv. of TMS-CH 2 -Li. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [165 mg, 82% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 6.39 (s, 1H), 1.99 (s, 2H), 0.01 (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 139.8, 123.7, 26.8, EI-MS m/z: 336, 335, 320, 248(100%), 73, 141, 73(100%). S8

9 (2-Methoxybenzyl)trimethylsilane (8): 2 Synthesized according to general method using 1-chloro-2- methoxybenzene. The product was obtained after column chromatography as a colorless liquid. (SiO 2, n-pentane). [109 mg, 94% yield]. 1 H-NMR (400MHz, Chloroform-d) δ 7.08 (td, J = 7.9, 1.7 Hz, 1H), 6.99 (dd, J = 7.4, 1.5 Hz, 1H), (m, 2H), 3.79 (s, 3H), 2.11 (s, 2H), (s, 9H). 13 C-NMR (100MHz, Chloroform-d) δ 156.4, 129.4, 129.2, 124.9, 120.2, 109.8, 54.8, 20.5, EI-MS m/z: 194, 179, 164, 149, 73(100%). 11 Mohapatra, S.K.; Romanov, A.; Timofeeva, T.V.; Marder, S.R.; Barlow, S. J. Organomet. Chem , 751, S9

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