Base free aryl coupling of diazonium compounds and boronic esters: Self activation allowing an ...

68 Pages·2009·7.14 MB·English

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Supporting Information

Base free aryl coupling of diazonium compounds and boronic esters: Self activation
allowing an overall highly practical process

Bonin-Dubarle Hélène,a Delbrayelle Dominiqueb Demonchaux Patriceb and Gras Emmanuela,c*!

a) CNRS, Université Paul Sabatier; LSPCMIB; 118, route de Narbonne, F-31062 Toulouse
Cedex 9
b) Minakem, 145, Chemin des Lilas, F-59310 Beuvry-La-Forêt, France
c) Present Address: CNRS; LCC; 205 route de Narbonne, F-31077 Toulouse, France;
Université de Toulouse; UPS; INPT; LCC; F31077 Toulouse, France E-mail:
[email protected]

1/ General details....................................................................................................S2
2/ 11B and 19F spectra of mixtures of phenyl pinacol boronic ester and fluoride
salt...........................................................................................................................S3
3/ Typical procedure for the synthesis of aryl dioxazaborocanes.....................S4
4/ Typical procedure for the synthesis of aryl diazoniums.................................S9
5/ Typical procedure for cross-coupling.............................................................S12
6/ 1H, 13C{1H}, 19F{1H}, 11B{1H} NMR spectra of dioxazaborocanes.....................S21
7/ 1H, 13C{1H}, 19F{1H}, 11B{1H} NMR spectra of diazoniums salts.......................S33
8/ 1H, 13C{1H}, 19F{1H} (when relevant) spectra of products of cross coupling.S45
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General details

All reactions requiring anhydrous conditions were conducted in a flame-dried apparatus
under an atmosphere of argon. THF and diethyl ether were distilled from Na/benzophenone.
All other reagents were used as received or when stated were purified according to standard
procedures (Armarego, W.L.F.; Chai, C. Purification of Laboratory Chemicals, 5th edition;
2003; Butterworth-Heinmann Ed.). Petrol ether refers to petroleum fraction boiling between
35°C and 70 °C. Chromatography columns were carried out on silica gel (35-70 !m).
1H, 13C{1H}, 11B{1H}, 19F{1H} NMR spectra were recorded with Bruker Advance spectrometers
at the specified frequencies. 1H and 13C chemical shifts are reported as " values (part per
million) relative to TMS and referenced to the internal residual undeuterated solvent. 11B
chemical shifts are reported as " values (part per million) relative to BF .Et O; Large patterns
3 2
appearing on 11B spectra from approximately -100 to 100 ppm correspond to the background
signal of the NMR tube and spectrometer probe. 19F chemical shifts are reported as " values
(part per million) relative to CFCl . Coupling constants (J) are given in Hz, multiplicities are
3
given as multiplet (m), singlet (s), doublet (d), triplet (t), quartet (q) or combination of where
applicable. Broadness of a signal is stated with its multiplicity (br). Mass spectra were
obtained from the “Service Commun de Spectrometrie de Masse de la Structure Fédérative
Toulousaine en Chimie Moléculaire” and recorded on a Thermoquest TSQ 7000
spectrometer.

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11B and 19F spectra of equimolar mixtures of phenyl pinacol boronic ester and
fluoride salt

With one molar equivalent of KF, the pic at 27.77 ppm correspond to the free
boronate ester; the one appearing at 5.18 ppm correspond to a ate complex
(donation of a fluoride anion into the empty orbital of the boron). The ate complex is
formed in a greater extent (and/or is more soluble with a Cs+ counterion) with one
molar equivalent of CsF accounting for an observed better reactivity.

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Typical procedure for the synthesis of aryl dioxazaborocanes (except for 2-fluoro-
3-methoxyphenyldioxazaborocane)

To a solution of bromoaryl (1 eq) in THF (2 mL/mmol, distilled) under argon at -78°C is added
n-BuLi (1 eq) at such a rate that the temperature is kept below -78°C. The resulting mixture is
stirred for 10 minutes at -78°C. B(OiPr) (1 eq) is then added at such a rate that the
3
temperature is kept below -78°C. The resulting white mixture is stirred for one hour while
allowed to warm to room temperature. Diethyl ether (20 mL) and NH Cl solution (20 mL)
4 sat
are then added, and the resultant mixture is stirred for 30 more minutes. The organic and
aqueous phases are separated, the aqueous phase is then extracted with ether (2X20 mL),
and the organic phases are washed with brine (2X5 mL). The organic phase is dried over
MgSO and filtered. The diethanolamine solution (i-PrOH, 3M, 1 eq) is added and the
4
resulting mixture is stirred for 10 minutes. A solid precipitates instantly. The mixture is
filtered, and the solid is washed with ether and dried under vacuum.
All the compounds are white solids, with melting points higher than 200°C.
Carbons bearing the boron atom are expectedly not detected in 13C NMR.

4,5,7,8-Tetrahydro-2-(2’-fluoro-3’-methoxyphenyl)-6H-[1,3,6,2]dioxazaborocane

This compound was made directly by addition of the 3M diethanolamine solution to the
corresponding boronic acid in ether.
O
B NH
O
O F

704 mg, 2.95 mmol, 98 % (from the corresponding boronic acid).
1H NMR (DMSO-d , 300 MHz), " = 7.08 (s br, 1H), 7.01 – 6.91 (m, 3H), 3.86 – 3.79 (td, J =
6
9.2 Hz, J = 5.4 Hz, 2H), 3.76 (s, 3H), 3.71 – 3.64 (m, 2H), 3.20 – 3.09 (tdd, J = 11.7 Hz, J =
9.2 Hz, J = 6.9 Hz, 2H), 2.85 – 2.78 (m, 2H).
13C NMR (DMSO-d , 75.5 MHz), " = 155.5 (d, 1J = 238 Hz), 147.1 (d, 2J = 14.4 Hz), 126.0 (d,
6
J = 10.8 Hz), 123.3 (d, J = 3.6 Hz), 112.8 (d, J = 1.6 Hz), 62.9, 56.2, 51.2.
11B NMR (DMSO-d , 96.3 MHz), " = 9.6.
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19F NMR (DMSO-d , 282.4 MHz), " = -129.4.
6
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MS(DCI-CH ): 240.1 [MH]+.
4
EA : C = 55.30 %, H = 6.61 %, N = 5.86 % (calculated for C H BFNO : C = 55.27 %, H =
11 15 3
6.32 %, N = 5.86 %)
IR (cm-1): 3147 (br), 2959, 2881, 1450, 1438, 1269, 1231, 1067, 770.

4,5,7,8-Tetrahydro-2-(phenyl)-6H-[1,3,6,2]dioxazaborocane
O
B NH
O

2.22 g, 11.6 mmol, 73 %.
1H NMR (DMSO-d , 300 MHz), " = 7.47 – 7.44 (m, 2H), 7.22 – 7.16 (m, 3H), 6.89 (s br, 1H),
6
3.90 – 3.83 (td, J = 9.2 Hz, J = 5.4 Hz, 2H), 3.81 – 3.74 (m, 2H), 3.14 – 3.02 (tdd, J = 11.7
Hz, J = 9.0 Hz, J = 6.9 Hz, 2H), 2.86 – 2.78 (m, 2H).
13C NMR (DMSO-d , 75.5 MHz), " = 133.1, 127.2, 126.8, 63.4, 51.2.
6
11B NMR (DMSO-d , 96.3 MHz), " = 10.9.
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MS(DCI-CH ): 192.1 [MH]+.
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EA : C = 62.65 %, H = 7.28 %, N = 7.27 % (calculated for C H BNO , C = 62.87 %, H =
10 14 2
7.39 %, N = 7.33 %).
IR (cm-1): 3118 (br), 2927, 2865, 1458, 1214, 1064, 751, 707.

4,5,7,8-Tetrahydro-2-(4’-methoxyphenyl)-6H-[1,3,6,2]dioxazaborocane

O
O B NH
O

2.73 g, 12.4 mmol, 77%.
1H NMR (DMSO-d , 300 MHz), " = 7.34 (d, J = 8.5 Hz, 2H), 6.76 (d, J = 8.5 Hz, 2H), 3.89-
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3.81 (td, J = 9.2 Hz, J = 5.4 Hz, 2H), 3.79-3.73 (m, 2H), 3.70 (s, 3H), 3.12-3.00 (tdd, J = 11.7
Hz, J = 9.0 Hz, J = 6.9 Hz, 2H), 2.85-2.77 (m, 2H).
13C NMR (DMSO-d , 75.5 MHz), " = 158.9, 134.2, 112.8, 63.4, 55.2, 51.1.
6
11B NMR (DMSO-d , 96.3 MHz), " = 10.8.
6
MS (DCI-NH , MeCN) m/z: 239.4 [M-NH ]+.
3 4
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EA : C = 59.43 %, H = 7.32 %, N = 6.21 % (calculated for C H BNO , C = 59.77 %, H =
11 16 3
7.30 %, N = 6.34 %)
IR (cm-1): 3137 (br), 3031, 2879, 2836, 1600, 1282, 1220, 1174, 1080, 1065, 818.

4,5,7,8-Tetrahydro-2-(4’-hydroxyphenyl)-6H-[1,3,6,2]dioxazaborocane

3 equivalents of t-BuLi were used instead of 1 equivalent of n-BuLi.
O
HO B NH
O

265 mg, 1.28 mmol, 63%.
1H NMR (DMSO-d , 300 MHz), " = 8.85 (s, 1H), 7.22 (d, J = 8.1 Hz, 2H), 6.71 (s, 1H), 6.60
6
(d, J = 8.1 Hz, 2H), 3.87 – 3.80 (td, J = 9.2 Hz, J = 5.4 Hz, 2H), 3.77 – 3.71 (m, 2H), 3.10 –
2.99 (tdd, J = 11.7 Hz, J = 9.2 Hz, J = 6.9 Hz, 2H), 2.82 – 2.75 (m, 2H).
13C NMR (DMSO-d , 75.5 MHz), " = 156.1, 133.6, 113.7, 62.8, 50.5.
6
11B NMR (DMSO-d , 96.3 MHz), " = 10.7.
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MS(DCI-CH ): 208.1 [MH]+; HRMS(DCI-CH ): 208.1146 [MH]+ (calculated for C H BNO :
4 4 10 15 3
208.1145).
IR (cm-1): 3180, 3099 (br), 2960, 28778, 1608, 1583, 1228, 1074, 831, 790.

4,5,7,8-Tetrahydro-2-(4’-formylphenyl)-6H-[1,3,6,2]dioxazaborocane

The protected 4-bromobenzaldehyde was used for the lithiation. The acidic hydrolysis was
done using HCl 2N/NaCl before addition of diethanolamine.
sat
O
B NH
O O

2.41 g, 11.0 mmol, 73%.
1H NMR (DMSO-d , 300 MHz), " = 9.89 (s, 1H), 7.67 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 8.1 Hz,
6
2H), 6.96 (s, 1H), 3.87-3.79 (td, J = 9.2 Hz, J = 5.4 Hz, 2H), 3.77-3.70 (m, 2H), 3.11-2.99
(tdd, J = 11.7 Hz, J = 9.0 Hz, J = 6.9 Hz, 2H), 2.85-2.78 (m, 2H).
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13C NMR (DMSO-d , 75.5 MHz), " = 193.9, 135.5, 133.7, 128.4, 63.6, 51.3.
6
11B NMR (DMSO-d , 96.3 MHz), " = 10.4.
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MS(DCI-CH ): 220.1 [MH]+; HRMS(DCI-CH ): 220.1148 [MH]+ (calculated for C H BNO :
4 4 11 15 3
220.1145).
IR (cm-1): 3137 (br), 2857, 1701, 1598, 1224, 1081, 784.

4,5,7,8-Tetrahydro-2-((1’,3’-dioxolan-2’-yl)phenyl)-6H-[1,3,6,2]dioxazaborocane

O
B NH
O
O
O

1.31 g, 5.0 mmol, 63 %.
1H NMR (DMSO-d , 300 MHz), " = 7.54 (s, 1H), 7.48 – 7.45 (m, 1H), 7.25 – 7.19 (m, 2H),
6
6.92 (s br, 1H), 5.66 (s, 1H), 4.07 – 3.99 (m, 2H), 3.98 – 3.91 (m, 2H), 3.90 – 3.83 (td, J = 9.2
Hz, J = 5.4 Hz, 2H), 3.82 – 3.75 (m, 2H), 3.14 – 3.02 (tdd, J = 11.7 Hz, J = 9.2 Hz, J = 6.9
Hz, 2H), 2.87 – 2.79 (m, 2H).
13C NMR (DMSO-d , 75.5 MHz), " = 136.4, 134.0, 131.5, 126.9, 125.3, 104.3, 65.2, 63.5,
6
51.2.
RMN 11B (DMSO-d , 96.3 MHz), " = 10.8.
6
MS(DCI-CH ): 264.1 [MH]+.
4
EA : C = 59.25 %, H = 7.18 %, N = 5.32 % (calculated for C H BNO : C = 59.35 %, H =
13 18 4
6.90 %, N = 5.32 %).
IR (cm-1): 3090 (br), 2892, 2854, 1431, 1284, 1159, 1071, 983, 782.

4,5,7,8-Tetrahydro-2-(3’-formylphenyl)-6H-[1,3,6,2]dioxazaborocane

The protected 3-bromobenzaldehyde was used for the lithiation. The acidic hydrolysis was
done using HCl 2N/NaCl before addition of diethanolamine.
sat
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O
B NH
O
O
1.11 g, 5.0 mmol, 63 %.
1H NMR (DMSO-d , 300 MHz), " = 9.99 (s, 1H), 7.99 (t, J = 1.3 Hz, 1H), 7.76 (td, J = 7.4 Hz,
6
J = 1.3 Hz, 1H), 7.70 (td, J = 7.4 Hz, J = 1.3 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.01 (s br, 1H),
3.93 – 3.87 (td, J = 9.2 Hz, J = 5.4 Hz, 2H), 3.84 – 3.78 (m, 2H), 3.17 – 3.05 (tdd, J = 11.7
Hz, J = 9.2 Hz, J = 6.9 Hz, 2H), 2.91 – 2.84 (m, 2H).
13C NMR (DMSO-d , 75.5 MHz), " = 194.1, 139.2, 135.0, 134.3, 127.7, 127.5, 63.1, 50.8.
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11B NMR (DMSO-d , 96.3 MHz), " = 10.7.
6
MS(DCI-CH ): 220.1 [MH]+.
4
EA : C = 58.67 %, H = 6.60 %, N = 6.26 % (calculated for C H BNO + 0.33 H O: C =
11 14 3 2
58.68%, H = 6.57 %, N = 6.22 %).
IR (cm-1): 3083 (br), 2863, 1692, 1588, 1464, 1284, 1198, 1144, 1067, 782.

4,5,7,8-Tetrahydro-2-(4’-cyanophenyl)-6H-[1,3,6,2]dioxazaborocane
Lithiation and addition of B(OiPr) were performed at -100°C.
3
O
N B NH
O

2.44 g, 11.3 mmol, 71%.
1H NMR (DMSO-d , 300 MHz), " = 7.61 (s, 4H), 3.93-3.85 (td, J = 9.2 Hz, J = 5.4 Hz, 2H),
6
3.83-3.76 (m, 2H), 3.16-3.05 (tdd, J = 11.8 Hz, J = 9.2 Hz, J = 6.9 Hz, 2H), 2.92-2.86 (m,
2H).
13C NMR (DMSO-d , 75.5 MHz), " = 133.9, 130.7, 120.3, 109.5, 63.4, 51.3.
6
11B NMR (DMSO-d , 96.3 MHz), " = 10.8.
6
MS(DCI-CH ): 217.1 [MH]+.
4
EA : C = 59.49 %, H = 6.13 %, N = 12.59 % (calculated for C H BN O + 0.33 H O: C =
11 13 2 2 2
59.52 %, H = 6.20 %, N = 12.62 %).
IR (cm-1): 3138 (br), 3040, 2865, 2218, 1466, 1279, 1236, 1072, 823, 786.
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Typical procedure for the synthesis of aryl diazoniums
To a suspension of the aniline (1 eq) in distilled water (0.4 mL/mmol) is added dropwise
HBF (50% wt in water, 1.7 eq). The mixture is cooled to 0°C, and the NaNO (1 eq) solution
4 2
in water (saturated solution) is added dropwise. During the addition, the temperature was
carefully kept below 5°C, and the resulting mixture was stirred at 0°C for 30 minutes. The
resulting precipitate was collected by filtration and dissolved in the minimum amount of
acetone. Diethyl ether was added until precipitation of a solid, which is filtered, washed with
ether and dried under vacuum.

4-nitrophenyl diazonium tetrafluoroborate

BF
O N N 4
2 2

Pale orange solid, 1.97 g, 8.3 mmol, 78 %
1H NMR (Acetone-d , 300 MHz), ": 9.07 (d, J = 9.7 Hz, 2H), 8.75 (d, J = 9.7 Hz, 2H).
6
13C NMR : the compound was not stable enough in solution to get the 13C NMR spectrum.
11B NMR (Acetone-d , 96.3 MHz), ": - 0.9.
6
19F NMR (Acetone-d , 282.4 MHz), ": - 151.4.
6
IR (cm-1): 3437, 3029, 2308, 1536, 1358, 1318, 1055, 858, 742
Ref : Microchimica Acta 2006, 152, 225 (1H)
4-methoxyphenyl diazonium tetrafluoroborate

BF
O N 4
2

Pale blue-grey solid, 1.80 g, 8.1 mmol, 75%.
1H NMR (Acetone-d +DMSO-d , 300 MHz), ": 8.72 (d, J = 9.3 Hz, 2H), 7.51 (d, J = 9.3 Hz,
6 6
2H), 4.13 (s, 3H).
13C NMR (Acetone-d +DMSO-d , 75.5 MHz), ": 169.3, 136.2, 117.3, 57.1.
6 6
11B NMR (DMSO-d , 96.3 MHz), ": - 0.9.
6
19F NMR (DMSO-d , 282.4 MHz), ": - 151.3.
6
IR (cm-1): 3430, 3115, 2992, 2240, 1583, 1290, 1100, 842.
Ref : J. Org. Chem. 2007, 72, 9609 (1H, 13C), J. Org. Chem. 2008, 73, 316 (IR).

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2-Acetophenyl diazonium tétrafluoroborates
BF
N 4
2
O

Pale orange solid, 706 mg, 5.0 mmol, 50 %
1H NMR (MeCN-d + Acetone-d , 300 MHz), ": 8.86 (dd, J = 8.1 Hz, J = 1.2 Hz, 1H), 8.59
3 6
(dd, J = 7.9 Hz, J = 1.2 Hz, 1H), 8.44 (td, J = 7.9 Hz, J = 1.2 Hz, 1H), 8.22 (dd, J = 8.1 Hz, J
= 1.2 Hz, 1H), 2.80 (s, 3H).
13C NMR (MeCN-d + Acetone-d , 75.5 MHz), ": 206.4, 141.6, 137.0, 136.2, 135.2, 133.3,
3 6
25.8.
11B NMR (MeCN-d + Acetone-d , 96.3 MHz), ": - 0.3.
3 6
19F NMR (MeCN-d + Acetone-d , 282.4 MHz), ": - 150.8.
3 6
IR (cm-1):3040, 2273, 1697, 1590, 1568, 1265, 1101, 1030, 773.

4-bromophenyl diazonium tetrafluoroborate

BF
Br N 4
2

White solid, 1.98 g, 7.3 mmol, 68 %
1H NMR (Acetone-d , 300 MHz), ": 8.76 (d, J = 9.3 Hz, 2H), 8.32 (d, J = 9.3 Hz, 2H).
6
13C NMR (DMSO-d , 75.5 MHz), ": 137.1, 135.0, 134.4, 115.5.
6
11B NMR (Acetone-d , 96.3 MHz), ": - 0.3.
6
19F NMR (Acetone-d , 282.4 MHz), ": - 150.8.
6
Ref : J. Org. Chem. 2008, 73, 316 (IR), Int. J. Mass. Spectro. 2002, 218, 131 (MS)

4-iodophenyl diazonium tetrafluoroborate

BF
I N 4
2

Pale yellow solid, 2.48 g, 7.8 mmol, 72 %
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