The Journal of Organic Chemistry
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134.0, 136.2, 139.2, 146.6. IR (CHCl3): 3421 cm−1. HRMS calcd for
C22H27BN3O2 (M + H)+ m/z: 376.2196, found 376.2193.
(1 H, dd, J = 7.0, 8.0 Hz), 7.65 (1 H, dd, J = 1.0, 8.0 Hz), 7.66 (2 H,
dd, J = 2.0, 8.5 Hz). 13C NMR (125 MHz, CDCl3) δ: −0.77, 55.6,
110.7, 114.9, 124.5, 127.3, 129.6, 130.2, 131.4, 133.9, 150.2, 159.6. IR
(CHCl3): 1520 cm−1. HRMS calcd for C16H19N3NaOSi (M + Na)+
m/z: 320.1195, found 320.1192.
1-(2-Iodobenzyl)-5-methyl-7-(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)-1H-benzo[d]triazole (proximal-10Bk) (Table
3, entry 13). Following the general procedure I, a mixture of 14B (58
mg, 97 μmol), 1-(azidomethyl)-2-iodobenzene 6k10c (76 mg, 0.29
mmol), and i-PrMgCl·LiCl (1.3 M in THF, 0.090 mL, 117 μmol) in
Et2O (1.0 mL, 0.10 M) was stirred for 30 min at 0 °C. The crude
product was purified by column chromatography (hexane/EtOAc =
5:1) to provide the titled compound proximal-10Bk (33 mg, 71%) as a
colorless solid. Mp 185−187 °C. 1H NMR (500 MHz, CDCl3) δ: 1.13
(12 H, s), 2.54 (3 H, s), 5.93 (1 H, dd, J = 1.0, 7.5 Hz), 6.22 (2 H, s),
6.91 (1 H, dt, J = 1.0, 7.5 Hz), 7.05 (1 H, t, J = 7.5 Hz), 7.88 (1 H, d, J
= 7.5 Hz), 7.90 (1 H, d, J = 1.0 Hz), 8.0 (1 H, brs). 13C NMR (125
MHz, CDCl3) δ: 21.1, 24.4, 58.4, 84.3, 95.9, 122.7, 125.7, 128.4, 128.6,
133.4, 134.8, 139.1, 139.7, 146.7. IR (CHCl3): 2982 cm−1. HRMS
calcd for C20H24BIN3O2 (M + H)+ m/z: 476.1006, found 476.1017.
Methyl 2-[(5-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)-1H-benzo[d]triazol-1-yl)methyl]benzoate (proximal-
10Bl) (Table 3, entry 14). Following the general procedure I, a
mixture of 14B (57 mg, 95 μmol), ethyl methyl 2-(azidomethyl)-
benzoate 6l40 (56 mg, 0.29 mmol), and i-PrMgCl·LiCl (1.3 M in THF,
0.090 mL, 117 μmol) in Et2O (1.0 mL, 0.10 M) was stirred for 30 min
at 0 °C. The crude product was purified by column chromatography
(hexane/EtOAc = 4:1) to provide the titled compound proximal-10Bl
1-(4-Methoxyphenyl)-7-(trimethylsilyl)-1H-benzo[d]triazole
(proximal-11Aa) (Table 1, entry 5). Product (7.9 mg, 10%) was
obtained by column chromatography of the above-mentioned crude
1
product as a colorless solid. Mp 106−109 °C. H NMR (500 MHz,
CDCl3) δ: 0.02 (9 H, s), 3.92 (3 H, s), 7.08 (2 H, dd, J = 2.0, 7.0 Hz),
7.39 (1 H, dd, J = 7.0, 7.5 Hz), 7.44 (2 H, dd, J = 2.0, 7.0 Hz), 7.70 (1
H, d, J = 7.0 Hz), 8.14 (1 H, d, J = 7.0 Hz). 13C NMR (125 MHz,
CDCl3) δ: 0.51, 55.7, 114.5, 121.3, 122.6, 123.6, 129.3, 130.9, 136.1,
138.3, 145.0, 160.9. IR (CHCl3): 1518 cm−1. HRMS calcd for
C16H19N3NaOSi (M + Na)+ m/z: 320.1195, found 320.1197.
1-(4-(tert-Butyl)phenyl)-6-methyl-4-(trimethylsilyl)-1H-
benzo[d]triazole (distal-11Bb) (Table 3, entry 1). Following the
general procedure II, a mixture of 16B14a (70 mg, 0.20 mmol), 1-
azido-4-(tert-butyl)benzene 6b35 (105 mg, 0.60 mmol), and Bu4NF
(1.0 M in THF, 0.40 mL, 0.40 mmol) in THF (2.0 mL) was stirred for
1.0 h. The ratio of distal- to proximal-11Bb (10:1) was determined
1
using H NMR spectra of the crude product. The crude product was
purified by column chromatography (hexane/EtOAc = 30:1) to
provide the titled compound distal-11Bb (42 mg, 61%) as a yellow
1
1
solid. Mp 92−94 °C. H NMR (500 MHz, CDCl3) δ: 0.52 (9 H, s),
(29 mg, 74%) as a colorless solid. Mp 127−129 °C. H NMR (500
1.40 (9 H, s), 2.53 (3 H, s), 7.32 (1 H, s), 7.49 (1 H,s), 7.61 (2 H, d, J
= 8.0 Hz), 7.68 (2 H, d, J = 8.0 Hz). 13C NMR (125 MHz, CDCl3) δ:
−0.7, 22.0, 31.3, 34.8, 110.2, 122.6, 126.6, 131.7, 131.9, 133.2, 134.7,
137.7, 149.0, 151.5. IR (CHCl3): 2964, 1600, 1519, 1411 cm−1. HRMS
calcd for C20H28N3Si (M + H)+ m/z: 338.2053, found 338.2055.
1-(4-(tert-Butyl)phenyl)-5-methyl-7-(trimethylsilyl)-1H-
benzo[d]triazole (proxiaml-11Bb) (Table 3, entry 1). Product (12
mg, 18%) was obtained by column chromatography of the above-
mentioned crude product as a colorless oil. 1H NMR (500 MHz,
CDCl3) δ: −0.02 (9 H, s), 1.40 (9 H, s), 2.53 (3 H, s), 7.43 (2 H, d, J
= 8.0 Hz), 7.51 (1 H, s), 7.58 (2 H, d, J = 8.0 Hz), 7.89 (1 H, s). 13C
NMR (125 MHz, CD3OD) δ: 0.4, 21.4, 31.3, 34.9, 120.1, 122.2, 126.3,
127.4, 133.3, 135.5, 136.7, 138.4, 145.8, 153.7. IR (CHCl3): 1602,
1514, 1261, 1236 cm−1. HRMS calcd for C20H28N3Si (M + H)+ m/z:
338/.2053, found 338.2059.
MHz, CDCl3) δ: 1.05 (12 H, s), 2.53 (3 H, s), 3.97 (3 H, s), 6.01 (1
H, d, J = 7.5 Hz), 6.73 (2 H, s), 7.21 (1 H, dt, J = 1.0, 7.5 Hz), 7.27 (1
H, dt, J = 1.0, 7.5 Hz), 7.86 (1 H, d, J = 1.0 Hz) 8.0 (1 H, brs) 8.11 (1
H, dd, J = 1.0, 7.5 Hz). 13C NMR (125 MHz, CDCl3) δ: 21.1, 24.3,
52.0, 52.7, 84.1, 122.6, 125.4, 126.7, 126.8, 131.1, 132.9, 133.3, 134.9,
139.3, 140.5, 146.7, 167.1. IR (CHCl3): 1717 cm−1. HRMS calcd for
C22H27BN3O4 (M + H)+ m/z: 408.2095, found 408.2100.
2-[(5-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-1H-benzo[d]triazol-1-yl)methyl]benzonitrile (proximal-
10Bm) (Table 3, entry 15). Following the general procedure I, a
mixture of 14B (62 mg, 102 μmol), 2-(azidomethyl)benzonitrile 6m41
(49 mg, 0.31 mmol), and i-PrMgCl·LiCl (1.3 M in THF, 0.10 mL, 124
μmol) in Et2O (1.0 mL, 0.10 M) was stirred for 30 min at 0 °C. The
crude product was purified by column chromatography (hexane/
EtOAc = 3:1) to provide the titled compound proximal-10Bm (30 mg,
1
78%) as a colorless solid. Mp 174−176 °C. H NMR (500 MHz,
1-(2,5-Dimethoxyphenyl)-6-methyl-4-(trimethylsilyl)-1H-
benzo[d]triazole (distal-11Bc) (Table 3, entry 2). Following the
general procedure II, a mixture of 16B14a (50 mg, 0.13 mmol), 2-
azido-1,4-dimethoxybenzene 6c10c (69 mg, 0.39 mmol), and Bu4NF
(1.0 M in THF, 0.26 mL, 0.26 mmol) in THF (1.3 mL) was stirred for
0.5 h. The ratio of distal- to proximal-11Bc (14:1) was determined
CDCl3) δ: 1.16 (12 H, s), 2.54 (3 H, s), 6.19−6.22 (1 H, m), 6.58 (2
H, s), 7.30−7.34 (2 H, m), 7.71−7.74 (1 H, m), 7.92 (1 H, d, J = 1.5
Hz), 8.01 (1 H, brs). 13C NMR (125 MHz, CDCl3) δ: 21.1, 24.4, 51.3,
84.4, 109.8, 117.1, 122.9, 125.5, 127.5, 132.7, 133.2, 133.7, 134.7,
140.0, 141.7, 146.7. IR (CHCl3): 2226 cm−1. HRMS calcd for
C21H24BN4O2 (M + H)+ m/z: 375.1992, found 375.1984.
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using H NMR spectra of the crude product. The crude product was
General Procedure II: Distal-Selective (3 + 2) Cycloadditions
of Silylbenzynes 5 (Tables 1 and 3). An oven-dried flask was
charged with a silylbenzyne precursor 16 (1.0 equiv), capped with a
rubber septum, and evacuated, and backfilled with argon. Anhydrous
THF (0.10 M) was added via a syringe, and the reaction mixture was
cooled to 0 °C. After 5 min, a dipole 6 (3.0 equiv) and Bu4NF (1.0 M
THF solution, 2.0 equiv) were added in that order, and the reaction
mixture was stirred at 0 °C for 30 min. The mixture was filtered
through a short pad of silica gel (hexane/EtOAc = 10:1 as the eluent).
The effluent mixture was concentrated under reduced pressure and
further purified by silica gel flash column chromatography to give silyl
benzazole 11.
1-(4-Methoxyphenyl)-4-(trimethylsilyl)-1H-benzo[d]triazole
(distal-11Aa) (Table 1, entry 5). Following the general procedure II,
a mixture of 16A17 (100 mg, 0.27 mmol), 1-azido-4-methoxybenzene
6a34 (124 mg, 0.83 mmol), and Bu4NF (1.0 M in THF, 0.54 mL, 0.54
mmol) in THF (2.7 mL, 0.10 M) was stirred for 30 min at 0 °C. The
ratio of distal- to proximal-11Aa (5.7:1) was determined using 1H
NMR spectra of the crude product. The crude product was purified by
column chromatography (hexane/EtOAc = 10:1 to 5:1) to provide the
titled compound distal-11Aa (39 mg, 49%) as a colorless solid. Mp
97−100 °C. 1H NMR (500 MHz, CDCl3) δ: 0.53 (9 H, s), 3.90 (3 H,
s), 7.11 (2 H, dd, J = 2.0, 8.5 Hz), 7.47 (1 H, dd, J = 1.0, 7.0 Hz), 7.51
purified by column chromatography (hexane/EtOAc = 15:1) to
provide the titled compound distal-11Bc (30 mg, 68%) as a colorless
solid, the regiochemistry of which was determined by NOESY
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spectrum. Mp 140−142 °C. H NMR (500 MHz, CDCl3) δ: 0.52 (9
H, s), 2.50 (3 H, s), 3.74 (3 H, s), 3.81 (3 H, s), 7.04 (1 H, d, J = 2.0
Hz), 7.07 (1 H, dd, J = 2.0, 8.0 Hz), 7.09 (1 H, d, J = 8.0 Hz), 7.13 (1
H, brs), 7.30 (1 H, d, J = 2.0 Hz). 13C NMR (125 MHz, CDCl3) δ:
−0.7, 22.0, 55.9, 56.5, 111.0, 113.4, 113.8, 116.2, 126.0, 131.65, 132.8,
133.3, 137.2, 147.7, 148.2, 153.8. IR (CHCl3): 2959, 1595, 1514 cm−1.
HRMS calcd for C18H24N3O2Si (M + H)+ m/z: 342.1638, found
342.1622.
1-(2,5-Dimethoxyphenyl)-5-methyl-7-(trimethylsilyl)-1H-
benzo[d]triazole (proximal-11Bc) (Table 3, entry 2). Product (2.7
mg, 6.0%) was obtained by column chromatography of the above-
1
mentioned crude product as a colorless solid. Mp 99−100 °C. H
NMR (500 MHz, CDCl3) δ: 0.01 (9 H, s), 2.53 (3 H, s), 3.64 (3 H, s),
3.81 (3 H, s), 6.99 (1 H, d, J = 8.0 Hz), 7.02 (1 H, d, J = 2.0 Hz), 7.11
(1 H, dd, J = 2.0, 8.0 Hz), 7.49 (1 H, s), 7.90 (1 H, s). 13C NMR (125
MHz, CD3OD) δ: 1.2, 22.1, 57.2, 57.3, 115.2, 118.4, 119.3, 121.1,
124.6, 128.5, 136.1, 139.5, 140.4, 147.1, 152.6, 155.6. IR (CHCl3):
2960, 1620, 1514 cm−1. HRMS calcd for C18H24N3O2Si (M + H)+ m/
z: 342.1638, found 342.1615.
J
dx.doi.org/10.1021/jo302802b | J. Org. Chem. XXXX, XXX, XXX−XXX