Synthesis, optical properties and regioselective functionalization of 4a-aza-10a-boraphenanthrene

Transcription

1 Synthesis, optical properties and regioselective functionalization of 4a-aza-10a-boraphenanthrene Alberto Abengózar, Patricia García-García,, * David Sucunza, Luis Manuel Frutos, Obis Castaño, Diego Sampedro, Adrián Pérez-Redondo and Juan J. Vaquero, * Departamento de Química Orga nica y Química Inorga nica, Universidad de Alcala, Alcala de Henares, Madrid, Spain. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain. Departamento de Química, Centro de Investigación en Síntesis Química (CISQ), Universidad de La Rioja, Madre de Dios 53, Logroño, Spain. Electronic Supplementary Information Table of Contents General Experimental Details S2 Experimental Procedures and Data S2 Synthesis of S2 Functionalization of 5 by reaction with electrophiles S5 Palladium-catalyzed cross-couplings reactions of 9a S7 Photophysical data of compounds 5, 9a, 9c and 9d S10 Computational photochemical study (CASPT2//CASSCF) S15 Computational details S15 Cartesian coordinates S15 Computational details for the regioselectivity of the electrophilic aromatic substitution S20 X-ray crystallographic data for 9a S21 Copies of 1 H, 13 C and 11 B NMR spectra for novel compounds and selected COSY, TOCSY, HSQC and HMBC spectra S24 S1

2 GENERAL EXPERIMENTAL DETAILS: Starting materials sourced from commercial suppliers were used as received unless otherwise stated. Dry solvents, where necessary, were dried by a MBRAUN MB-SPS-800 apparatus. Reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25 mm E. Merck silica gel plates (60FS-254) using UV light for visualization. Column chromatography was performed using silica gel (60 F254, mm) as the stationary phase. All melting points were determined in open capillary tubes on a Stuart Scientific SMP3 melting point apparatus. IR spectra were obtained on a Perkin Elmer FTIR spectrum 2000 spectrophotometer. 1 H, 13 C and 11 B NMR spectra were recorded on either a Varian Mercury VX-300, Varian Unity 300 or Varian Unity 500 MHz spectrometer at room temperature. Chemical shifts are given in ppm ( ) downfield from TMS. Coupling constants (J) are in hertz (Hz) and signals are described as follows: s, singlet; d, doublet; t, triplet; q, quadruplet; m, multiplet; b, broad; ap, apparent. High-resolution analysis (HRMS) were performed on an Agilent 6210 time of-flight LC/MS. Elemental analysis were performed in a LECO CHNSO-932 instrument. o-bromostyrene was prepared as described previously. 1 Absorption spectra were recorded in a UV-Vis Uvikon 941 (Kontron Instruments) spectrophotometer. Steady-state fluorescence measurements were carried out by using a PTI Quanta Master spectrofluorimeter equipped with a Xenon flash lamp as a light source, single concave grating monochromators and Glan- Thompson polarizers in the excitation and emission paths. Detection was allowed by a photomultiplier cooled by a Peltier system. Slit widths were selected at 6 nm for both excitation and emission paths and polarizers were fixed at the magic angle condition. Right angle geometry and rectangular 10 mm path cells were used for the fluorescence measurements. EXPERIMENTAL PROCEDURES AND DATA Synthesis of 5: Synthesis of N-(but-3-en-1-yl)-2-vinylaniline (6) To an oven-dried Biotage microwave vial equipped with a stir bar were added [PdCl(allyl)]2 (11 mg, mmol, 0.5 mol%), JohnPhos (18 mg, mmol, 1.0 mol%), and t-buona (0.818 g, 8.26 mmol, 1.4 eq.). The vial was sealed with a cap lined with a disposable Teflon septum, evacuated under vacuum, and purged with argon three times. Toluene (10 ml) was added, followed by 2-bromostyrene (1.080 g, 5.9 mmol, 1.0 eq.) and 3-butenylamine (668 L, g, 7.10 mmol, 1.2 eq.). The resulting mixture was heated to 80 ºC and stirred until full consumption of 2-bromostyrene was observed by TLC (48 h). The reaction mixture was cooled to room temperature, diluted with Et2O (20 ml), and filtered over Celite. The solvent was removed in vacuo, and the product was purified by flash column chromatography on silica gel (hexanes/etoac 99:1). The product was obtained as a yellow oil (0.945 g, 5.45 mmol, 93%). IR (NaCl) ῦmax (cm -1 ) 3421, 3077, 2923, 2849, 1602, 1509, 1458, 1314, 1263, 912, Dieltiens, N.; Stevens, C. V. Synlett, 2006, 17, S2

3 1 H-NMR (300 MHz, CDCl3) (ppm) 7.25 (dd, J = 7.5, 1.6 Hz, 1H, H-3), (m, 1H, H-5), (m, 1H, H-4), 6.72 (dd, Jtrans = 17.4 Hz, Jcis = 11.0 Hz, 1H, H-7), 6.64 (d, J = 8.2 Hz, 1H, H-6), 5.84 (ddt, Jtrans = 17.1 Hz, Jcis = 10.2 Hz, J = 6.8 Hz, 1H, H-11), 5.59 (dd, Jtrans = 17.4 Hz, Jgem = 1.6 Hz, 1H, H-8), 5.30 (dd, Jcis = 11.0 Hz, Jgem = 1.6 Hz, 1H, H-8), 5.17 (ap dq, Jtrans = 17.1 Hz, J = 1.5 Hz, 1H, H-12), (m, 1H, H-12), 3.85 (bs, 1H, NH), 3.21 (t, J = 6.8 Hz, 2H, H-9), 2.42 (ap qt, J = 6.8, 1.5 Hz, 2H, H-10). 13 C-NMR (75 MHz, CDCl3) (ppm) (C-1), (C-11), (C-7), (C-3), (C-5), (C-2), (C-4), (C-6), (C-8), (C-12), 42.8 (C-9), 33.6 (C-10). HRMS (APCI-TOF) calculated for C12H16N [M+H] + : ; found [M+H] + : Synthesis of 1-(but-3-en-1-yl)-2-vinyl-1-aza-2-boranaphthalene (7) To an oven-dried Biotage microwave vial equipped with a stir bar was added potassium vinyltrifluoroborate (495.0 mg, 3.51 mmol, 1.0 eq.). The vial was sealed with a cap lined with a disposable Teflon septum, evacuated under vacuum, and purged with argon three times. CMPE (7 ml) and toluene (7 ml) were added, followed by the 2-aminostyrene 6 (730.0 mg, 4.21 mmol, 1.2 eq.), SiCl4 (406 L, mg, 3.51 mmol, 1.0 eq.) and Et3N (734 L, mg, 5.27 mmol, 1.5 eq.) under argon. The resulting mixture was heated to 80 ºC for 72 h. Then the reaction mixture was cooled to room temperature, diluted with Et2O (15 ml), filtered over a plug of silica gel and flushed with Et2O (50 ml). The solvent was removed in vacuo and the resulting product was purified via flash column chromatography on silica gel (hexanes) to provide the desired product a pale yellow oil (607.0 mg, 2.90 mmol, 83%). IR (NaCl) ῦmax (cm -1 ) 3059, 2979, 2918, 1610, 1553, 1417, 1353, 1288, 1217, 949, 917, 806, H-NMR (500 MHz, CDCl3) (ppm) 7.95 (d, J = 11.4 Hz, 1H, H-4), 7.63 (dd, J = 7.8, 1.7 Hz, 1H, H-5), 7.53 (d, J = 8.6 Hz, 1H, H-8), 7.49 (ddd, J = 8.6, 6.8, 1.7 Hz, 1H, H-7), 7.18 (ddd, J = 7.8, 6.8, 1.4 Hz, 1H, H-6), 7.03 (d, J = 11.4 Hz, 1H, H-3), 6.73 (dd, Jtrans = 19.4 Hz, Jcis = 13.6 Hz, 1H, H-13), 6.23 (dd, Jtrans = 19.4 Hz, Jgem = 3.7 Hz, 1H, H-14), 6.09 (dd, Jcis = 13.6 Hz, Jgem = 3.7 Hz, 1H, H-14), 5.91 (ddt, Jtrans = 17.1 Hz, Jcis = 10.3 Hz, J = 6.8 Hz, 1H, H-11), 5.14 (ap dq, Jtrans = 17.1 Hz, J = 1.6 Hz, 1H, H-12), 5.10 (ap dq, Jcis = 10.3 Hz, J = 1.6 Hz, 1H, H-12), (m, 2H, H-9), (m, 2H, H-10). 13 C-NMR (125 MHz, CDCl3) (ppm) (C-4), (C-8a), (C-11), (C-14), (C-13*), (C-5), (C-7), (C-3*), (C-4a), (C-6), (C-12), (C-8), 46.2(C-9), 34.3 (C-10). *Carbon not observed in 13 C NMR, assigned by ghsqc. 11 B-NMR (128 MHz, CDCl3) (ppm) HRMS (APCI-TOF) calculated for C14H17BN [M+H] + : ; found [M+H] + : S3

4 Synthesis of 3,4-dihydro-4a-aza-10a-boraphenanthrene (8) The ruthenium catalyst Grubbs Second Generation (61.0 mg, mmol, 10 mol%) in dry CH2Cl2 (1.2 ml) was added to a solution of the diene 7 (150.0 mg, mmol, 1.0 eq.) in dry CH2Cl2 (6 ml) under an argon atmosphere. The reaction mixture was stirred at 40 ºC for 24 h. Then the reaction mixture was cooled to room temperature, diluted with CH2Cl2 (10 ml), filtered over a plug of silica gel and flushed with CH2Cl2 (20 ml). The solvent was removed in vacuo and the resulting product was purified via flash column chromatography on silica gel (hexanes) to afford the product 8 as a pale yellow oil (125.0 mg, mmol, 96%). IR (NaCl) ῦmax (cm -1 ) 3009, 2927, 2868, 2830, 1607, 1548, 1421, 1294, 1213, 1174, 811, H-NMR (500 MHz, CDCl3) (ppm) 7.96 (d, J = 11.3 Hz, 1H, H-7), 7.62 (dd, J = 7.8, 1.8 Hz, 1H, H-8), 7.56 (d, J = 8.6 Hz, 1H, H-11), 7.48 (ddd, J = 8.6, 6.9, 1.8 Hz, 1H, H-10), 7.15 (ddd, J = 7.8, 6.9, 1.2 Hz, 1H, H- 9), 6.82 (d, J = 11.3 Hz, 1H, H-6), 6.76 (dt, J = 11.7, 4.1 Hz, 1H, H-3), 6.33 (dt, J = 11.7, 1.7 Hz, 1H, H-4), 4.03 (t, J = 7.3 Hz, 2H, H-1), 2.57 (tdd, J = 7.3, 4.1, 1.7 Hz, 2H, H-2). 13 C-NMR (125 MHz, CDCl3) (ppm) (C-7), (C-3), (C-11a), (C-8), (C-4*), (C-6*), (C-10), (C-7a), (C-9), (C-11), 42.2 (C-1), 28.3 (C-2). *Carbon not observed in 13 C NMR, assigned by ghsqc. 11 B-NMR (128 MHz, CDCl3) (ppm) HRMS (APCI-TOF) calculated for C12H13BN [M+H] + : ; found [M+H] + : Synthesis of 4a-aza-10a-boraphenanthrene (5) In a round bottom flask equipped with a stir bar the BN-phenanthrene derivative 8 (50.0 mg, mmol, 1.0 eq.) was dissolved in decane (4 ml). Then Pd/C 30% was added (20.0 mg, 40%), and the reaction was heated to 140 ºC and stirred until full consumption of 8 was observed by TLC (24 h). Afterwards the reaction mixture was cooled to room temperature, diluted with CH2Cl2 (5 ml), and filtered over Celite. The solvent was removed in vacuo and the product was purified by flash column chromatography on silica gel (hexanes) to give the desired product as a white solid (42.0 mg, mmol, 84%). M.p.: ºC. IR (KBr) ῦmax (cm -1 ) 3012, 1614, 1598, 1476, 1420, 1274, 798, 733. S4

5 1 H-NMR (500 MHz, CDCl3) ppm) 8.67 (d, J = 7.5 Hz, 1H, H-1), 8.21 (d, J = 8.7 Hz, 1H, H-11), 8.00 (d, J = 11.4 Hz, 1H, H-7), (m, 1H, H-3), 7.80 (dd, J = 7.8, 1.9 Hz, 1H, H-8), 7.60 (ddd, J = 8.7, 7.0, 1.9 Hz, 1H, H-10), (m, 2H, H-4, H-9), 7.36 (d, J = 11.4 Hz, 1H, H-6), 6.80 (ddd, J = 7.5, 6.1, 1.8 Hz, 1H, H-2). 13 C-NMR (125 MHz, CDCl3) (ppm) (C-7), (C-3), (C-11a), (C-4*), (C-6*), (C-8), (C-1), (C-10), (C-7a**), (C-9), (C-11), (C-2). *Carbon not observed in 13 C NMR, assigned by ghsqc. ** Carbon not observed in 13 C NMR, assigned by ghmbc. 11 B-NMR (128 MHz, CDCl3) (ppm) MS (DIP-EI) m/z (relative intensity) 179 (M +, 100). Elemental analysis calculated for C12H10BN ( g/mol): C, 80.51; H, 5.63; N, Found: C, 80.44; H, 5.58; N, Functionalization of 5 by reaction with electrophiles Synthesis of 4-bromo-4a-aza-10a-boraphenanthrene (9a) A mixture of AlCl3 (56.0 mg, 0.42 mmol, 1.5 eq.) and N-bromosuccinimide (NBS) (75.0 mg, 0.42 mmol, 1.5 eq.) was loaded in a Schlenk flask under argon. Dichloromethane (10 ml) was added and the mixture was stirred at 25 ºC for 30 min and then cooled to 35 ºC. The resulting solution was treated with a solution of 5 (50.0 mg, 0.28 mmol, 1.0 eq.) in 10 ml of dichloromethane and stirred 2 h at 35 ºC. After solvent removal, hexane was added and the mixture was filtered to remove the insoluble. The filtrate was further concentrated to dryness. Purification of the resulting residue by flash column chromatography on silica gel (hexanes) afforded the product 9a as white solid (74.0 mg, 0.28 mmol, 99%). M.p.: ºC. IR (KBr) ῦmax (cm -1 ) 2924, 1614, 1599, 1416, 1346, 1253, 981, 801, 740, H-NMR (500 MHz, CDCl3) (ppm) 8.61 (d, J = 7.4 Hz, 1H, H-1), 8.16 (d, J = 8.8 Hz, 1H, H-11), 8.04 (d, J = 11.5 Hz, 1H, H-7), 7.97 (d, J = 7.0 Hz, 1H, H-3), 7.80 (dd, J = 7.8, 1.9 Hz, 1H, H-8), 7.61 (ddd, J = 8.8, 7.0, 1.9 Hz, 1H, H-10), 7.53 (d, J = 11.5 Hz, 1H, H-6), (m, 1H, H-9), 6.61 (ap t, J = 7.2 Hz, 1H, H- 2). 13 C-NMR (125 MHz, CDCl3) (ppm) (C-7), (C-3), (C-11a), (C-8), (C-4**), (C-6*), (C-10), (C-7a), (C-1), (C-9), (C-11), (C-2). *Carbon not observed in 13 C-NMR, assigned by ghsqc. **Carbon not observed in 13 C-NMR, assigned by ghmbc. 11 B-NMR (128 MHz, CDCl3) (ppm) MS (DIP-EI) m/z (relative intensity): 257 (M +, 100). S5

6 Elemental analysis calculated for C12H9BBrN ( g/mol): C, 55.88; H, 3.52; N, Found: C, 55.82; H, 3.79; N, Synthesis of 4-chloro-4a-aza-10a-boraphenanthrene (9b) A mixture of AlCl3 (45.0 mg, 0.34 mmol, 1.5 eq.) and N-chlorosuccinimide (NCS) (46.0 mg, 0.34 mmol, 1.5 eq.) was loaded in a Schlenk flask under argon. Dichloromethane (8 ml) was added and the mixture was stirred at 25 ºC for 30 min and then cooled to 35 ºC. The resulting solution was treated with a solution of 5 (40.0 mg, 0.22 mmol, 1.0 eq.) in 8 ml of dichloromethane and stirred 2 h at 35 ºC. After solvent removal, hexane was added and the mixture was filtered to remove the insoluble. The filtrate was further concentrated to dryness. Purification of the resulting residue by flash column chromatography on silica gel (hexanes) afforded the product 9b as white solid (34.0 mg, 0.16 mmol, 72%). M.p.: ºC. IR (KBr) ῦmax (cm -1 ) 2925, 1615, 1594, 1417, 1350, 1276, 1257, 993, 803, 741, H-NMR (500 MHz, CDCl3) (ppm) 8.57 (d, J = 7.4 Hz, 1H, H-1), 8.17 (d, J = 8.8 Hz, 1H, H-11), 8.05 (d, J = 11.5 Hz, 1H, H-7), 7.81 (dd, J = 7.8, 1.7 Hz, 1H, H-8), 7.72 (dd, J = 7.1, 0.8 Hz, 1H, H-3), 7.62 (ddd, J = 8.8, 7.1, 1.7 Hz, 1H, H-10), 7.56 (d, J = 11.5 Hz, 1H, H-6), 7.44 (ddd, J = 7.8, 7.1, 1.1 Hz, 1H, H-9), 6.67 (ap t, J = 7.2 Hz, 1H, H-2). 13 C-NMR (125 MHz, CDCl3) (ppm) (C-7), (C-4**), (C-3), (C-11a), (C-8), (C-10), (C-7a), (C-6*), (C-1), (C-9), (C-11), (C-2). *Carbon not observed in 13 C NMR, assigned by ghsqc. **Carbon not observed in 13 C NMR, assigned by ghmbc. 11 B-NMR (128 MHz, CDCl3) (ppm) HRMS (EI) calculated for C12H9BClN [M] + : Found [M] + : Synthesis of 1,1'-(propane-1,1-diyl)di(4a-aza-10a-boraphenanthrene) (10) A mixture of AlCl3 (112.0 mg, 0.84 mmol, 10.0 eq.) and propionaldehyde (62 L, 50.0 mg, 0.84 mmol, 10.0 eq.) was loaded in a Schlenk flask under argon. Dichloromethane (9 ml) was added and the mixture was stirred at 25 ºC for 30 min and then cooled to 35 ºC. The resulting solution was treated with a solution of 5 (30.0 mg, 0.17 mmol, 2.0 eq.) in 9 ml of dichloromethane and stirred 2 h at 35 ºC. After addition of water (20 ml) and extraction with dichloromethane (3x20 ml), the combined organic layers were dried over S6

7 Na2SO4, filtered and concentrated to dryness. The resulting residue was purified by flash column chromatography on silica gel (hexanes/etoac 99:1) to give 10 as white solid (27.0 mg, mmol, 80%). M.p.: ºC. IR (KBr) ῦmax (cm -1 ) 2957, 2926, 1617, 1598, 1481, 1418, 1276, 802, H-NMR (500 MHz, CDCl3) (ppm) 8.48 (d, J = 7.3 Hz, 2H, H-1, H-19), 8.17 (d, J = 8.7 Hz, 2H, H-11, H- 21), 7.92 (d, J = 11.6 Hz, 2H, H-7, H-25), 7.73 (dd, J = 7.8, 1.8 Hz, 2H, H-8, H-24), (m, 2H, H-10, H-22), 7.55 (d, J = 11.6 Hz, 2H, H-6, H-26), 7.47 (d, J = 6.7 Hz, 2H, H-3, H-17), (m, 2H, H-9, H- 23), 6.70 (ap t, J = 7.0 Hz, 2H, H-2, H-18), 5.06 (t, J = 7.3 Hz, 1H, H-13), 2.12 (ap q, J = 7.3 Hz, 2H, H-14), 1.04 (t, J = 7.3 Hz, 3H, H-15). 13 C-NMR (125 MHz, CDCl3) (ppm) (2C, C-4, C-16)**, (2C, C-7, C-25), (2C, C-11a, C- 20a), (2C, C-3, C-17), (2C, C-8, C-24), (2C, C-6, C-26)*, (2C, C-10, C-22), (2C, C-7a, C-24a), (2C, C-1, C-19), (2C, C-9, C-23), (2C, C-11, C-21), (2C, C-2, C-18), 47.1 (C-13), 30.2 (C-14), 13.7 (C-15). *Carbon not observed in 13 C NMR, assigned by ghsqc. **Carbon not observed in 13 C NMR, assigned by ghmbc. 11 B-NMR (128 MHz, CDCl3) (ppm) HRMS (EI) calculated for C27H24B2N2 [M] + : Found [M] + : Palladium-catalyzed cross-couplings reactions of 9a Synthesis of 1-phenyl-4a-aza-10a-boraphenanthrene (9c) In a round bottom flask equipped with a stir bar the brominated BN-phenanthrene 9a (40.0 mg, 0.16 mmol, 1.0 eq.) and phenylboronic acid (28.0 mg, 0.22 mmol, 1.4 eq.) were dissolved in 0.64 ml toluene and 0.16 ml methanol and treated with a suspension of Na2CO3 (400.0 mg) in 1.6 ml of water. Then Pd(PPh3)4 (9.2 mg, mmol, 5 mol%) was added and the mixture was heated to 70 ºC and stirred overnight. After addition of water (10 ml) and extraction with dichloromethane (3x10 ml), the combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The crude organic product was purified by flash column chromatography on silica gel (hexanes/dichloromethane 98:2) to give 9c as white solid (31.0 mg, 0.12 mmol, 76%). M.p.: ºC. IR (KBr) ῦmax (cm -1 ) 3017, 2924, 1611, 1597, 1490, 1415, 1354, 1256, 801, 746, H-NMR (500 MHz, CDCl3) (ppm) 8.70 (d, J = 7.3 Hz, 1H, H-1), 8.25 (d, J = 8.7 Hz, 1H, H-11), 8.00 (d, J = 11.6 Hz, 1H, H-7), 7.80 (dd, J = 7.7, 1.9 Hz, 1H, H-8), 7.70 (d, J = 6.6 Hz, 1H, H-3), 7.63 (ddd, J = 8.7, S7

8 7.0, 1.9 Hz, 1H, H-10), (m, 2H, H-14, H-18), (m, 1H, H-9), (m, 2H, H-15, H- 17), 7.42 (d, J = 11.6 Hz, 1H, H-6), 7.35 (tt, J = 7.3, 1.7 Hz, 1H, H-16), 6.86 (ap t, J = 7.0 Hz, 1H, H-2). 13 C-NMR (125 MHz, CDCl3) (ppm) (C-4**), (C-13), (C-7), (C-3), (C-11a), (C-8), (C-6*), (2C, C-14, C-18), (2C, C-15, C-17), (C-10), (C-7a), (C-1), (C-16), (C-9), (C-11), (C-2). *Carbon not observed in 13 C NMR, assigned by ghsqc. **Carbon not observed in 13 C NMR, assigned by ghmbc. 11 B-NMR (128 MHz, CDCl3) (ppm) HRMS (EI) calculated for C18H14BN [M] + : Found [M] + : Synthesis of 1-(N-morpholinyl)-4a-aza-10a-boraphenanthrene (9d) To an oven-dried Biotage microwave vial equipped with a stir bar were added [PdCl(allyl)]2 (1.5 mg, mmol, 2.5 mol%), JohnPhos (2.4 mg, mmol, 5.0 mol%), and t-buona (22.0 mg, 0.22 mmol, 1.4 eq.). The vial was sealed with a cap lined with a disposable Teflon septum, evacuated under vacuum, and purged with argon three times. Toluene (0.32 ml) was added, followed by brominated BN-phenanthrene 9a (40.0 mg, 0.16 mmol, 1.0 eq.) and morpholine (16 L, 16.0 mg, 0.19 mmol, 1.2 eq.). The resulting mixture was heated to 80 ºC and stirred until full consumption of 9a was observed by TLC (24 h). The reaction mixture was cooled to room temperature, diluted with Et2O (5 ml), and filtered over Celite. The solvent was removed in vacuo, and the resulting product was purified by flash column chromatography on silica gel (hexanes/etoac 9:1). The product was obtained as yellow oil (35.0 mg, 0.13 mmol, 83%). IR (NaCl) ῦmax (cm -1 ) 2957, 2851, 1613, 1519, 1417, 1372, 1262, 1223, 1115, 1022, 935, 805, H-NMR (500 MHz, CDCl3) (ppm) 8.24 (d, J = 7.4 Hz, 1H, H-1), 8.15 (d, J = 8.7 Hz, 1H, H-11), 7.96 (d, J = 11.5 Hz, 1H, H-7), 7.76 (dd, J = 7.8, 2.0 Hz, 1H, H-8), 7.58 (ddd, J = 8.7, 7.0, 2.0 Hz, 1H, H-10), 7.39 (ap t, J = 7.4 Hz, 1H, H-9), 7.36 (d, J = 11.5 Hz, 1H, H-6), 6.84 (d, J = 7.2 Hz, 1H, H-3), 6.62 (ap t, J = 7.3 Hz, 1H, H-2), (m, 4H, H-15, H-17), (m, 4H, H-14, H-18). 13 C-NMR (125 MHz, CDCl3) (ppm) (C-4**), (C-7), (C-11a), (C-8), (C-6*), (C-10), (C-7a), (C-9), (C-1), (C-3), (C-11), (C-2), 67.3 (2C, C- 15, C-17), 53.2 (2C, C-14, C-18). *Carbon not observed in 13 C NMR, assigned by ghsqc. **Carbon not observed in 13 C NMR, assigned by ghmbc. 11 B-NMR (128 MHz, CDCl3) (ppm) HRMS (ESI + ) calculated for C16H18BN2O [M+H] + : Found [M+H] + : S8

9 Synthesis of 1-(phenylethynyl)-4a-aza-10a-boraphenanthrene (9e) To an oven dried Schlenk flask charged with 9a (40.0 mg, 0.16 mmol, 1.0 eq.), phenylacetylene (52 L, 48.0 mg, 0.48 mmol, 3.0 eq.), Pd(PPh3)2Cl2 (5.6 mg, mmol, 5 mol%) and CuI (1.5 mg, mmol, 5 mol%) was added triethylamine (67 L, 49.0 mg, 0.48 mmol, 3.0 eq.) and DMF (1.6 ml). The mixture was heated and stirred at 80 ºC for 24 h. The resulting mixture was successively washed with water (15 ml) and extracted with dichloromethane (3x10 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The resulting product was purified by flash column chromatography on silica gel (hexanes to hexanes/dichloromethane 97:3) to give the desired product as a pale yellow solid (37.0 mg, 0.13 mmol, 83%). M.p.: ºC. IR (KBr) ῦmax (cm -1 ) 3037, 2926, 1603, 1477, 1416, 1351, 1267, 1252, 809, 756, H-NMR (500 MHz, CDCl3) ppm) 8.66 (d, J = 7.3 Hz, 1H, H-1), 8.19 (d, J = 8.7 Hz, 1H, H-11), 8.06 (d, J = 11.5 Hz, 1H, H-7), 7.93 (d, J = 6.4 Hz, 1H, H-3), 7.81 (dd, J = 7.8, 1.8 Hz, 1H, H-8), 7.69 (d, J = 11.5 Hz, 1H, H-6), (m, 3H, H-10, H-16, H-20), (m, 1H, H-9), (m, 2H, H-17, H-19), (m, 1H, H-18), 6.79 (ap t, J = 7.0 Hz, 1H, H-2). 13 C-NMR (125 MHz, CDCl3) (ppm) (C-3), (C-7), (C-11a), (2C, C-16, C-20), (C-8), (C-6*), (C-10), (2C, C-17, C-19), (C-7a**), (C-1), (C-18), (C-4**), (C-15), (C-9), (C-11), (C-2), 94.8 (C-14), 92.1 (C-13). *Carbon not observed in 13 C NMR, assigned by ghsqc. **Carbon not observed in 13 C NMR, assigned by ghmbc. 11 B-NMR (128 MHz, CDCl3) (ppm) HRMS (ESI + ) calculated for C20H15BN [M+H] + : Found [M+H] + : S9

10 PHOTOPHYSICAL DATA OF COMPOUNDS 5, 9a, 9c and 9d Compound Solvent (M -1 cm -1 ) excitation (nm) emission (nm) F (%) 5 Dichloromethane a 5 Cyclohexane b 9a Cyclohexane b 9c Cyclohexane b 9d Cyclohexane b F = Quantum yield. a Reported relative to Quinine sulfate ( F = 0.55). b Reported relative to 9,10-Diphenylanthracene ( F = 0.93). Absorption spectra of 5. a) Full spectrum in dichloromethane. b) Detail of the nm region in cyclohexane (black line) and dichloromethane (red line) a) b) Normalized Absorption (a. u.) 1,2 1,1 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0, (nm) UV Spectra of 5 Normalized Absorption (a. u.) 1,2 1,1 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0, (nm) CH DCM Figure S1 S10

11 Emission spectra of 5 in cyclohexane (black line) and dichloromethane (red line) Normalized Fluorescence (a. u.) 1,2 1,1 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0, (nm) CH DCM Figure S2 S11

12 Effect of concentration in the absorption spectra and emission spectra of the compound 5 (cyclohexane was used as solvent) Absorption Intensity (a. u.) 1,2 1,1 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0, (nm) 0,180 mm 0,090 mm 0,045 mm 0,023 mm Figure S3 Fluorescence Intensity (a. u.) A = 0,3264 a. u. A = 0,2349 a. u. A = 0,2026 a. u (nm) Figure S4 S12

13 Absorption spectra (black line) and emission spectra (red line) of compound 9a Normalized Intensity (a. u.) 1,2 1,1 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0, (nm) Absorption spectra Emission spectra Figure S5 Absorption spectra (black line) and emission spectra (red line) of compound 9c Normalized Intensity (a. u.) 1,2 1,1 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0, (nm) Absorption spectra Emission spectra Figure S6 S13

14 Absorption spectra (black line) and emission spectra (red line) of compound 9d Normalized Intensity (a. u.) 1,2 1,1 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0, (nm) Absorption spectra Emission spectra Figure S7 S14

15 COMPUTATIONAL PHOTOCHEMICAL STUDY (CASPT2//CASSCF) Computational details The computational photochemical study was performed using the Multi-State Complete Active Space Perturbation to Second Order with a Complete active Space Self Consistent Field reference wavefunction (MS-CASPT2//SA-CASSCF) methodology. 2,3 In this case, the State Averaged-Complete Active Space Self Consistent Field (SA-CASSCF) method was used to compute the critical points along the potential energy surface and the minimum energy paths (MEPs) connecting them. For both 2 and 5, the active space chosen includes the complete set of π and π* orbitals and the nitrogen atom lone pair (14 electrons in 14 orbitals). The absorption spectra were computed at the MS-CASPT2//SA-CASSCF level of theory for the ground state minima including four states (S0, S1, S2 and S3) with the same weight in the averaged wavefunction. The minima in S1 were calculated from the Franck Condon structure by using the steepest descent algorithm. The electronic states crossings were optimized at the CASSCF level and the two non-adiabatic coupling vectors defining the branching plane (gradient difference and derivative coupling) were computed. The dynamic correlation for the critical points was included at the MS-CASPT2 level of theory. CASSCF calculations were performed with the Gaussian 09 software 4 while MOLCAS 8.0 was used for the calculation of the CASPT2 single point energy corrections. 5 Both CASSCF and CASPT2 calculations have been performed with the ANO-L-VDZ basis set. Cartesian Coordinates 2-S0 C C C C C C C C C C Roos, B. O.; Taylor, P. R.; Siegbahn, P. E. M. Chem. Phys. 1980, 48, Andersson, K.; Malmqvist, P.-Å.; Roos, B. O. J. Chem. Phys. 1992, 96, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;Robb, M. A.; Cheeseman; J. R.; Scalmani; G.; Barone; V.; Mennucci;B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M. N.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision B.01; Gaussian, Inc.: Wallingford, CT, F. Aquilante, J. Autschbach, R. K. Carlson, L. F. Chibotaru, M. G. Delcey, L. De Vico, I. Fdez. Galván, N. Ferré, L. M. Frutos, L. Gagliardi, M. Garavelli, A. Giussani, C. E. Hoyer, G. Li Manni, H. Lischka, D. Ma, P. Å. Malmqvist, T. Müller, A. Nenov, M. Olivucci, T. B. Pedersen, D. Peng, F. Plasser, B. Pritchard, M. Reiher, I. Rivalta, I. Schapiro, J. Segarra Martí, M. Stenrup, D. G. Truhlar, L. Ungur, A. Valentini, S. Vancoillie, V. Veryazov, V. P. Vysotskiy, O. Weingart, F. Zapata, R. Lindh, J. Comp. Chem. 2016, 37, 506. S15

16 C C B N H H H H H H H H H H MinS1 C C C C C C C C C C C C B N H H H H H H H H H H TS C C C C C C C B H H H H C C C C C N H H H H H H CI C C C C S16

17 C C C B H H H H C C C C C N H H H H H H S0 C C C C C C C C C H C C C H H H H H H H H H N B MinS1 C C C C C C C C C H C C C H H H H H H H H H N B S17

18 3-TS N C C C C C C C C B C C C C H H H H H H H H H H CI N C C C C C C C C B C C C C H H H H H H H H H H S0 C C C C C C C C C C C C B N H H H S18

19 H H H H H H H MinS1 C C C C C C C C C C C C B N H H H H H H H H H H CI C C C C C C C B H H H H C C C C C N H H H H H H S19

20 COMPUTATIONAL DETAILS FOR THE REGIOSELECTIVITY OF THE ELECTROPHILIC AROMATIC SUBSTITUTION In order to identify all the possible intermediates of the aromatic substitution (arenium cations), a systematic identification and study of all the possible attacks (i.e. from 1 to 10 following the numbering in Figure 5 of the main text) of the electrophile (i.e. bromine cation) was performed. The energies of each specie were determined by optimizing each structure at the CAM-B3LYP level of theory using a 6-31G(d,p) basis set as implemented in Gaussian 09 (see reference 4 of previous section). Analytical gradients were employed to determine the stationary structures, while analytical hessians permitted to characterize each optimized intermediate as minima, sowing in all cases only positive frequencies. The most stable arenium cation is the result of the bromine cation attack on C1. Attack on C3 renders the second more stable species (6.55 kca/mol above the C1 attack intermediate), and the rest of potential intermediates fall well-above this energy. Therefore, by applying a Boltzmann distribution, the predicted equilibrium populations confirm the C1 substituted species as the most probable. According to the calculated energies, the equilibrium populations at 300K are ca. ~99.99% for C1 attack, while less than 0.01% for C3, being the population of the remaining potential intermediates completely negligible. Fukui function for electrophilic attack (i.e. electron density difference between neutral and cationic species) has been determined in order to rationalize the regioselective attack. As can be seen in Figure S8, the highest tendency to donate π-charge corresponds to atoms C1, C3, C4 and C9. This finding goes in line with the relative stability of each intermediate determined by electronic-structure calculations, nevertheless, it cannot provide a quantitative frame accounting for the experimental findings, but in any case it renders a first scenario for chemical reactivity. Figure S8. Fukui function for the electrophilic attack in the 4a-aza-10a-boraphenanthrene compound. C1, C3, C4 and C9 shows the most prominent π-charge contribution to the function, denoting their ability to facilitate the attack of the electrophilic species E +. S20

21 X-RAY CRYSTALLOGRAPHIC DATA FOR 9a Colourless crystals were grown by slow evaporation of a toluene solution. The crystals were removed from the vial and covered with a layer of a viscous perfluoropolyether (FomblinY). A suitable crystal, selected with the aid of a microscope, was mounted on a cryoloop and placed in the low temperature nitrogen stream of the diffractometer. The intensity data sets were collected at 200 K on a Bruker-Nonius KappaCCD diffractometer equipped with an Oxford Cryostream 700 unit. The structure was solved, using the WINGX package, 6 by direct methods (SHELXS-2013) 7 and refined by least-squares against F 2 (SHELXL-2014/7). 8 All non-hydrogen atoms were anisotropically refined, whereas the hydrogen atoms were positioned geometrically and refined by using a riding model. Figure S9. X-ray structure and numbering scheme for 9a. Thermal ellipsoids are drawn at the 50% probability level. 6 Farrugia, L. J. J. Appl. Crystallogr. 2012, 45, Sheldrick, G. M Acta Crystallogr. 2008, A64, Sheldrick, G. M. Acta Crystallogr. 2015, C71, 3. S21

22 Figure S10a. Crystal packing in a herringbone pattern for molecules of 9a. Figure S10b. Parallel and antiparallel orientations of B N bonds for neighbouring molecules. Nitrogen and boron atoms are represented as blue and pink spheres, respectively. S22

23 Table S1. Experimental data for the X-ray diffraction study on compound 9a formula C12H9BBrN Mr T [K] 200 [Å] crystal system space group monoclinic P21/c a [Å] 4.208(2) b [Å]; (º) (4); 95.97(4) c [Å] (11) V [Å 3 ] (8) Z 4 calcd [g cm -3 ] MoK [mm -1 ] F(000) 512 crystal size [mm 3 ] range (deg) index ranges 5 to 5 13 to to 26 reflns collected unique data 2359 [R(int) = 0.071] obsd data [I > 2 (I)] 1800 GOF on F final R a indices [I > 2 (I)] R1 = wr2 = R a indices (all data) R1 = wr2 = largest diff. peak/hole [e Å -3 ] and a R1 = ǀǀF0ǀ ǀFcǀǀ/[ ǀF0ǀ]; wr2 = {[ w(f0 2 Fc 2 ) 2 ]/[ w(f0 2 ) 2 ]} S23

24 S24

25 S25

26 S26

27 S27

28 S28

29 S29

30 S30

31 S31

32 S32

33 S33

34 S34

35 S35

36 S36

37 S37

38 S38

39 S39

40 S40

41 S41

42 S42

43 S43

44 S44

45 S45

46 S46

47 S47

48 S48

49 S49

50 S50

51 S51

52 S52

53 S53

54 S54

55 S55

56 S56

57 S57

58 S58

59 S59

60 S60

61 S61

62 S62

63 S63

64 S64

65 S65

66 S66

67 S67

68 S68

69 S69

70 S70

71 S71

72 S72

73 S73

74 S74

75 S75

76 S76

77 S77

78 S78

79 S79

80 S80

81 S81

82 S82

83 S83

84 S84

85 S85

86 S86

87 S87