Modular Synthesis of Elongated Phosphonate Bipyridines
1
1
50.20, 146.27, 138.95, 133.43, 131.41, 120.74, 120.45, 119.65,
crystallographic data for 7. These data can be obtained free of
C,P = 137.9 Hz), 16.60 ppm. P NMR charge from The Cambridge Crystallographic Data Centre via
, 25 °C): δ = 25.28 ppm. HRMS (MALDI): m/z www.ccdc.cam.ac.uk/data_request/cif. General remarks: amine pro-
calcd. for [M + H] 743.26188; found 743.26195. IR (KBr): ν˜ = tons were assigned to appropriate electron density maxima, and
17.65, 62.51, 33.61 (d, 1
J
31
(162 MHz, CDCl
3
+
3
1
445, 3115, 3085, 2984, 2907, 2114, 1605, 1519, 1416, 1387, 1249,
031, 964, 858, 782, 717, 551 cm . Crystals suitable for X-ray distance was chosen according to the default effective N–H dis-
their positions were fixed using the DFIX command. The N–H
–1
analysis were obtained by slow evaporation of chloroform.
tance as suggested following refinement with the TEMP command.
–
1
3Ј-Azido-4-diethyl(methylene)phosphonate-1,1Ј-biphenyl (8): This
compound was prepared by a modified literature procedure.
Compound 7 (1.97 mmol, 630 mg) was dissolved in a mixture of
water (15 mL) and concentrated hydrochloric acid (7.5 mL). The
Crystal Data for L2: C36
prism, crystal size 0.1121ϫ0.0939ϫ0.0288 mm , monoclinic,
space group P 2 /n, a = 8.5104(2) Å, b = 14.6092(3) Å, c =
5.2627(5) Å, β = 105.580(2)°, V = 1827.89(7) Å , T = 150(2) K, Z
40 8 6 2 r
H N O P , M = 742.70 gmol , yellow
[
42]
3
1
3
1
3
–1
2
solution was cooled to 0 °C, NaNO (338 mg, 4.90 mmol) in water
=
2, ρcalcd. = 1.557 Mg/m , μ (Cu-K
altogether 9020 reflexes up to h(–9/10), k(–18/13), l(–19/18) mea-
sured in the range of 7.497° Յ Θ Յ 74.491°, completeness Θmax
9.7%, 3724 independent reflections, Rint = 0.0190, 3217 reflections
with F Ͼ 4σ(F ), 235 parameters, 0 restraints, R1obs = 0.0536,
wR2obs = 0.1557, R1all = 0.0612, wR2all = 0.1650, GOOF = 1.055,
α
) = 1.557 mm , F(000) = 780,
(
2 mL) were added, and the resulting solution was stirred for
5 min. Then NaN (319 mg, 4.91 mmol) in water (2 mL) was
added, and the reaction mixture was stirred for 1 h at 0 °C and
.5 h at room temperature. The resulting solution was extracted
several times with CHCl and EtOAc. The combined organic ex-
4
3
=
9
3
o
o
3
–3
tracts were dried with anhydrous MgSO , and the EtOAc was evap-
largest difference peak and hole: 0.790/–0.527 eÅ . CCDC-
400582 contains the supplementary crystallographic data for L2.
These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
4
1
orated to afford the product 8 (681 mg, quantitative yield).
NMR (400 MHz, CDCl
H
=
1
3
, 25 °C): δ = 7.45 (s, 1 H), 7.43 (s, 1 H),
4
3
7
7
2
.35–7.26 (m, 4 H), 7.13 (t, JH,H = 1.8 Hz, 1 H), 6.93 (d, JH,H
.8 Hz, 1 H), 4.04–3.91 [m, 4 H, PO(OCH CH
H,H = 7.1 Hz, 6 H,
2
3 2
) ], 3.15 (d, J =
3
1.8 Hz, 2 H, CH
2
-PO
3
Et
2
), 1.18 [t,
J
Diethyl (4-Bromobenzyl)phosphonate (5): This compound was pre-
13
PO(OCH
2
CH ] ppm. C NMR (101 MHz, CDCl
3
)
2
3
, 25 °C): δ =
pared according to literature.[
45]
1
42.64, 140.59, 138.87, 131.16, 130.44, 130.24, 127.36, 123.76,
1
31
3
Ј-Amino-4-diethyl(methylene)phosphonate-1,1Ј-biphenyl (7): The
reaction flask was charged with 3-aminophenlyboronic acid
2.03 mmol, 315 mg), 5 (2.03 mmol, 624 mg), toluene (60 mL), and
degassed aqueous sodium carbonate solution (2 m, 21 mL) under
argon. Then the first portion of Pd(PPh (6 mol-% based on 5)
was added to the solution. After one day of boiling at reflux, a
second portion of Pd(PPh (35 mg) was added, and the solution
117.89, 117.67, 62.64, 33.38 (d, JC,P = 138.4 Hz), 16.48 ppm.
P
3
NMR (162 MHz, CDCl , 25 °C): δ = 27.95 ppm. HRMS (ESI):
m/z calcd. for [M + H]+ 346.13150; found 346.13139. IR (KBr): ν˜
(
= 2983, 2907, 2104, 1564, 1480, 1401, 1304, 1249, 1096, 1027, 962,
–
1
3
)
4
853, 784, 693, 604, 544 cm .
L3: This compound was prepared by a modified literature pro-
3
)
4
[44]
cedure.
Compound 8 (0.70 g, 2.03 mmol) was added to a solu-
Cl (30 mL), which was fol-
lowed by the addition of a mixture of copper sulfate pentahydrate
80 mg, 0.32 mmol) and (+)-sodium (L)-ascorbate (NaAsc; 155 mg,
.79 mmol) in H O (30 mL). Upon the addition of the aqueous
was heated to reflux for an additional 24 h. After the mixture
cooled to room temperature, the toluene was evaporated. The crude
tion of 4 (178 mg, 0.87 mmol) in CH
2
2
product was extracted several times with CH
2
Cl
2
, and the com-
. CH Cl
2
(
bined organic extracts were dried with anhydrous MgSO
4
2
0
2
was evaporated, and the product was purified by flash chromatog-
raphy using 9:1 EtOAc/MeOH as the eluent (630 mg, 97% yield).
H NMR (400 MHz, CDCl , 25 °C): δ = 7.38 (d, JH,H = 8.0 Hz,
3
H), 7.22 (dd, JH,H = 8.2, JH,H = 2.3 Hz, 2 H), 7.05 (t, JH,H
.8 Hz, 1 H), 6.82 (d, JH,H = 7.7 Hz, 1 H), 6.75 (s, 1 H), 6.51 (dd,
suspension to the orange organic phase, a black precipitate formed
instantly. The mixture was stirred for 12 h and then poured into a
saturated aqueous ethylenediaminetetraacetic acid (EDTA) solu-
1
3
3
4
3
2
=
2+
tion (600 mL) and stirred for 14 h to remove Cu . The resulting
3
7
blue solution was extracted several times with CHCl
bined organic extracts were dried with anhydrous MgSO
CHCl was evaporated to afford the crude product. Flash
chromatography using 5:1 CHCl /MeOH as the eluent gave the
product as a brownish oil with some impurities. This oil was diluted
with CHCl , and title compound was obtained by precipitation
with n-pentane as a brownish powder in 30% yield (235 mg). H
NMR (400 MHz, CDCl , 25 °C): δ = 8.81 (m, 4 H), 8.61 (s, 2 H),
3
. The com-
3
4
J
H,H
=
7.9,
CH
H,H = 7.1 Hz, 6 H, PO(OCH
101 MHz, CDCl , 25 °C): δ = 146.70, 142.02, 139.99, 130.73,
J
H,H
=
1.6 Hz,
1
H), 3.97–3.84 [m,
], 3.06 (d, JH,P = 21.6 Hz, 2 H, CH -PO Et
CH ] ppm. C NMR
4
H,
), 1.13
4
, and the
2
PO(OCH
2
3
)
2
2
3
13
2
3
3
[t,
J
2
3 2
)
3
(
1
=
2
3
1
30.13, 129.81, 127.30, 117.70, 114.30, 113.91, 62.33, 33.55 (d, JC,P
3
138 Hz), 16.54 ppm. 31P NMR (162 MHz, CDCl
, 25 °C): δ =
1
3
+
7.60 ppm. HRMS (ESI): m/z calcd. for [M + H] 320.14101;
3
–
1
found 320.14122. IR (KBr): ν˜ = 3573, 2260, 1020, 668, 447 cm .
Crystals suitable for X-ray analysis were obtained by slow evapora-
tion of chloroform.
3
4
4
8
2
7
.08 (dd, JH,H = 5.0, JH,H = 1.7 Hz, 2 H), 8.04 (t, JH,H = 1.7 Hz,
H), 7.76 (d, JH,H = 7.8 Hz, 2 H), 7.68 (d, JH,H = 7.9 Hz, 2 H),
.63 (m, 6 H), 7.44 (dd, JH,H = 8.3, JH,H = 2.4 Hz, 4 H), 4.10–
4.02 [m, 8 H, PO(OCH CH ) ], 3.25 (d, J
3
3
3
4
2
–1
H,P 2
= 21.8 Hz, 4 H, CH -
Crystal Data for 7: C17
H
22
N
1
O
3
P
1
, M
r
= 319.32 gmol , colourless
fragment, crystal size 0.3494ϫ0.2048ϫ0.1369 mm , monoclinic,
space group P1, a = 8.8460(4) Å, b = 9.9740(6) Å, c = 10.1215(5) Å,
α = 109.307(5)°, β = 92.340(4)°, γ = 96.862(4)°, V = 833.68(8) Å ,
2
3 2
1
3
3
PO Et ), 1.28 [t, J = 7.1 Hz, 12 H, PO(OCH CH ) ] ppm.
C
3
2
2
3 2
¯
NMR (101 MHz, CDCl
3
, 25 °C): δ = 156.47, 150.20, 146.27,
3
142.94, 138.94, 138.15, 137.36, 132.06, 130.64, 130.46, 127.76,
1
3
127.44, 120.44, 119.85, 119.26, 117.65, 62.36, 33.60 (d, JC,P =
T = 150(2) K, Z = 2, ρcalcd. = 1.272 Mg/m , μ (Mo-K
α
) =
3
1
–1
3
138.3 Hz), 16.52 ppm. P NMR (162 MHz, CDCl , 25 °C): δ =
0
1
2
.177 mm , F(000) = 340, altogether 10151 reflexes up to h(–10/
1), k(–12/12), l(–12/12) measured in the range of 3.411° Յ Θ Յ
6.370°, completeness Θmax = 99.7%, 3396 independent reflections,
2
6.09 ppm. HRMS (MALDI): m/z calcd. for [M + H]+ 895.32448;
found 895.32441. IR (KBr): ν˜ = 3350, 3282, 2923, 2852, 2334, 1868,
739, 1233, 1022, 789, 717, 666, 545, 442 cm .
–
1
1
Rint = 0.0307, 2769 reflections with F
o o
Ͼ 4σ(F ), 206 parameters,
2
restraints, R1obs = 0.0460, wR2obs = 0.1065, R1all = 0.0583,
Supporting Information (see footnote on the first page of this arti-
cle): Experimental and characterization data, as well as additional
figures.
wR2all = 0.1144, GOOF = 1.055, largest difference peak and hole:
–3
0.407/–0.353 eÅ . CCDC-1400580 contains the supplementary
Eur. J. Org. Chem. 2015, 5987–5994
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5993