10.1002/chem.201904164
Chemistry - A European Journal
FULL PAPER
NMR (600.130 MHz, CDCl3) δH 6.06 (s, 2H, ArH), 3.36-3.33 (m, 2H, CH2),
2.71-2.69 (m, 2H, CH2), 2.52 (s, 6H, 2CH3), 2.45 (s, 6H, 2CH3) ppm; IR
(C=O) = 1688.71 cm-1, (O-H) = 3266.60 cm-1; Rf (EtOAc) = 0.3 (stained
with bromocresol green).
Compound 15: An oven dried round bottomed flask was equipped with a
Dean-Stark trap and charged with benzaldehyde (0.110 mL, 1.10 mmol,
2.20 eq.), piperidine (2.00 mL) and AcOH (2.00 mL). The flask was flushed
with argon before methyl 5,5-difluoro-1,3,7,9-tetramethyl-5H-4λ4,5λ4-
dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinine-10-carboxylate (150 mg, 0.490
mmol, 1.00 eq.) in dry toluene (20.0 mL) was added. The flask was
equipped with a Dean and Stark trap and the reaction mixture was heated
under reflux for 16 hours. After cooling to room temperature, the reaction
mixture was washed with distilled water (3 x 20.0 mL) and the organic
material was extracted with DCM, dried over MgSO4, filtered and
concentrated in vacuo. The residue was purified by flash column
chromatography on silica gel; eluent: DCM/MeOH from a ratio of 100/0 to
90/10. The fractions containing product were combined and concentrated
by evaporation to afford methyl 5,5-difluoro-1,9-dimethyl-3,7-di((E)-styryl)-
5H-4λ4,5λ4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinine-10-carboxylate as a
blue solid (140 mg, 0.290 mmol, 59%). 1H-NMR (700 MHz, CDCl3) δH 7.70
(d, J = 16.4 Hz, 2H, C=CH), 7.53 (d, J = 16.3 Hz, 4H, PhH), 7.42 (m, 6H,
PhH), 7.10 (d, J = 16.4 Hz, 2H, C=CH), 6.72 (s, 2H, ArH), 4.01 (s, 3H, CH3),
2.20 (s, 6H, 2CH3) ppm; 11B-NMR (224 MHz, CDCl3) δB 0.98 (t, J = 33.3
Hz) ppm; 19F-NMR (658 MHz, CDCl3) δF -138.3 ppm; MS (ESI)
C29H25BF2N2O2 (m/z 483.2, [M+H]+; IR (C=O) = 1735.80 cm-1; Rf (DCM) =
0.2.
Compounds 11 and 12: Compound 1 or 5 were dissolved in dry THF (10
mL) under argon and cooled to -78 °C. NIS (3.9 eq.) was added and the
reaction warmed to room temperature overnight. The solvent was
evaporated and the crude purified by flash column chromatography on
silica gel; eluent: hexane/DCM:50/50. Compound 11: (5,5-difluoro-2,8-
diiodo-1,3,7,9-tetramethyl-5H-4λ4,5λ4-dipyrrolo[1,2-c:2',1'-
f][1,3,2]diazaborinin-10-yl)methyl acetate (61.0 mg, 0.109 mmol, 33%) 1H
NMR (600.130 MHz, CDCl3) δH 4.01(s, 3H, OCH3), 2.64 (s, 6H, 2CH3),
2.14 (s, 6H, 2CH3) ppm; 11B-NMR (224 MHz, CDCl3) δB 0.38 (t, J = 30.5
Hz) ppm; 19F-NMR (658 MHz, CDCl3) δF -145.7 (q, J = 31.6 Hz) ppm; IR
(C=O) = 1737.11 cm-1; Rf (hexane/DCM:50/50) = 0.2. Compound 12:
methyl
5,5-difluoro-2,8-diiodo-1,3,7,9-tetramethyl-5H-4λ4,5λ4-
dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinine-10-carboxylate (52.0 mg, 0.091
mmol, 29%) 1H NMR (600.130 MHz, CDCl3) δH 5.32 (s, 2H, CH2), 2.63 (s,
6H, 2CH3), 2.40 (s, 6H, 2CH3), 2.15 (s, 3H CH3) ppm; 13C NMR (151 MHz,
CDCl3) δC 170.4, 158.1, 143.6, 132.9, 132.7, 87.4, 58.4, 20.7, 18.3, 16.5
ppm; 11B-NMR (224 MHz, CDCl3) δB 0.36 (t, J = 33.3 Hz) ppm; 19F-NMR
(658 MHz, CDCl3) δF -145.6 (q, J = 31.6 Hz) ppm; IR (C=O) = 1740.76 cm-
1; Rf (hexane/DCM:50/50) = 0.4.
Compound 16: Dry toluene (30.0 mL) was degassed with argon for 30
minutes. 10-(bromomethyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4λ4,5λ4-
dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinine (80.0 mg, 0.235 mmol) was
added followed by diethylaminobenzaldehyde (92.0 mg, 0.517 mmol, 2.2
eq.). AcOH (2.00 mL) and piperidine (2.00 mL) were added and the
reaction mixture was stirred under reflux and under argon overnight. The
organic material was extracted using DCM and the organic layers washed
with water, dried over MgSO4, filtered and concentrated by evaporation.
The crude solid was purified by flash column chromatography on silica gel;
eluent: hexane/DCM. The fractions containing product were combined and
concentrated under vacuum to afford 4,4'-((1E,1'E)-(10-(bromomethyl)-
5,5-difluoro-1,9-dimethyl-5H-4λ4,5λ4-dipyrrolo[1,2-c:2',1'-
f][1,3,2]diazaborinine-3,7-diyl)bis(ethene-2,1-diyl))bis(N,N-diethylaniline)
as a green/blue solid (10.0 mg, 0.0160 mmol, 7%). 1H-NMR (700 MHz,
CDCl3) δH 7.47 (d, J = 8.8 Hz, 4H, ArH), 7.45 (d, J = 16.7 Hz, 2H, C=CH),
7.20 (d, J = 16.1 Hz, 2H, C=CH), 6.67 (s, 2H, CH), 6.64 (d, J = 8.8 Hz, 4H,
ArH) 3.72 (s, 2H CH2Br), 3.40 (q, J = 7.1 Hz, 8H, CH2CH3), 2.51 (s, 6H,
CH3), 1.19 (t, J = 7.1 Hz, 12H, CH2CH3) ppm; 11B-NMR (224 MHz, CDCl3)
δB 0.86 (t, J = 33.3 Hz) ppm; 19F-NMR (658 MHz, CDCl3) δF -142.5 ppm;
Rf (hexane/EtOAc:60/40) = 0.3.
Compound 13: A solution of (5,5-difluoro-1,3,7,9-tetramethyl-5H-4λ4,5λ4-
dipyrrolo[1,2-c:2',1'-f][1,3,2] diazaborinin-10-yl)methyl acetate (100 mg,
0.310 mmol) was prepared in dry toluene (300 mL). Methyl 4-ethynyl
benzoate (124 mg, 0.775 mmol, 2.50 eq.), Pd(tetrakis) (10.4 mg, 0.00900
mmol, 3.00 mol%), CuI (3.00 mg, 0.0160 mmol, 5.00 mol%) and TEA (3.00
mL) were added and the reaction mixture stirred under reflux overnight.
The reaction mixture was filtered through a plug of celite using EtOAc and
the crude product dried under vacuum. The material was purified using
flash column chromatography on silica gel; eluent: hexane/EtOAc:10/90.
The fractions containing product were combined and concentrated in
vacuo to afford 4,4'-((5,5-difluoro-1,3,7,9,10-pentamethyl-5H-4λ4,5λ4-
dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinine-2,8-diyl)bis(ethyne-2,1-
diyl))dibenzoate as an amorphous purple solid (27.0 mg, 0.0467 mmol,
15%). 1H-NMR (700 MHz, CDCl3) δH 8.03 (d, 4H, J = 8.5 Hz, PhH), 7.57
(d, 4H, J = 8.5 Hz, PhH), 3.94 (s, 6H, COOCH3), 2.71 (s, 3H, CH3), 2.70
(s, 6H, 2CH3), 2.60 (s, 6H, 2CH3) ppm; 11B-NMR (224 MHz, CDCl3) δB 0.59
(t, J = 30.5 Hz) ppm; 19F-NMR (658 MHz, CDCl3) δF -146.6 (q, J = 31.6 Hz)
ppm; IR (C=O) = 1719.33 cm-1; Rf (hexane/EtOAc:20/80) = 0.1.
HiBO: Dry DCM (150 mL) was purged with argon for 30 min. Bromoacetyl
bromide (0.170 mL, 1.90 mmol, 1 eq.) and 2,4-dimethylpyrrole (0.400 mL,
3.90 mmol, 2 eq.) were added dropwise and the dark red reaction mixture
was stirred at room temperature under argon and protected from the light
for three hours. The solvent was reduced to ~50 mL under vacuum and
triethylamine (4.00 mL, 29.0 mmol, 15 eq.) was added. After 15 min of
stirring under argon, BF3·Et2O (8.00 mL, 65.0 mmol, 33 eq.) was added
dropwise. The reaction mixture was stirred for a further three hours under
argon and protected from the light. DCM (3 x 30 mL) was used to extract
the organic material which was washed with distilled water (3 x 30 mL),
dried over MgSO4, filtered and concentrated in vacuo. The crude red
product was purified by flash column chromatography on silica gel; eluent:
hexane/DCM from a ratio of 80/20 to 50/50. The fractions containing
product were combined and concentrated by evaporation to afford 10-
(bromomethyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4λ4,5λ4-dipyrrolo[1,2-
c:2',1'-f][1,3,2]diazaborinine (224 mg, 0.660 mmol, 35%) as a red solid. 1H-
NMR (600 MHz, CDCl3) δH 6.09 (s, 2H, CH), 4.69 (s, 2H, CH2Br), 2.54 (s,
12H, 4CH3) ppm; 13C-NMR (151 MHz, CDCl3) δC 156.6, 141.0, 137.3,
131.1, 122.4, 24.7, 16.1, 14.8 ppm; MS (EI) C14H16BBrF2N2 (m/z 340.1,
Compound 14: A solution of (5,5-difluoro-1,3,7,9-tetramethyl-5H-4λ4,5λ4-
dipyrrolo[1,2-c:2',1'-f][1,3,2] diazaborinin-10-yl)methyl acetate (100 mg,
0.310 mmol) was prepared in dry toluene (30 mL). 4-ethynyl-N,N-
dimethylaniline (113 mg, 0.775 mmol, 2.50 eq.), Pd(tetrakis) (10.4 mg,
0.009 mmol, 3.0 mol%), CuI (3.00 mg, 0.0160 mmol, 5.00 mol%) and TEA
(3.00 mL) were added and the reaction mixture stirred under reflux
overnight. The reaction mixture was filtered through a plug of celite using
EtOAc and the crude product dried under vacuum. The material was
purified using flash column chromatography on silica gel; eluent:
hexane/EtOAc:50/50. The fractions containing product were combined
and concentrated by evaporation to yield 4,4'-((5,5-difluoro-1,3,7,9,10-
pentamethyl-5H-4λ4,5λ4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinine-2,8-
diyl)bis(ethyne-2,1-diyl))bis(N,N-dimethylaniline) as an amorphous purple
solid (21.0 mg, 0.0383 mmol, 12%). 1H NMR (700 MHz, CDCl3) δH 7.40 (d,
4H, J = 8.9 Hz, PhH), 6.67 (d, 4H, J = 8.7 Hz, PhH), 3.00 (s, 12H, 2N(CH3)2),
2.68 (s, 6H, 2CH3), 2.67 (s, 3H, CH3), 2.56 (s, 6H, 2CH3) ppm; 11B NMR
(224 MHz, CDCl3) δB 0.46 (t, J = 33.3 Hz) ppm; 19F NMR (658 MHz, CDCl3)
δF – 146.9 (q, J = 31.9 Hz) ppm; Rf (hexane/EtOAc:50/50) = 0.2.
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