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tion was started with the rapid addition of both isotopes of 1 and
[4-D1]1 (250 mmol each). Aliquots (50 mL) of the reaction mixtures
were taken every 30 min in a 5 mL vial containing tert-butyl methyl
ether (2.0 mL). The solution was extracted immediately with an
aqueous solution of sodium hydroxide (1.0m, 0.60 mL); the organic
layer was separated and analyzed with GLC and GLC-MS.
and GLC-MS in accordance with 1H NMR spectroscopy measure-
ments. 1H NMR (500 MHz, C6D6): d=6.86 (d, 4J=3.0 Hz, 1H), 6.82
4
3
(d, J=3.0 Hz, 1H), 3.88 (q, J=7.2 Hz, 2H), 3.32 (s, 2H), 0.89 ppm
3
(t, J=7.2 Hz, 3H); 13C NMR (126 MHz, C6D6): d=170.4, 134.2, 128.6
1
(t, J(C,D)=25.7 Hz), 125.6, 122.9, 60.6, 35.9, 14.2 ppm; IR (ATR): n˜ =
3105, 2980, 2935, 1730, 1365, 1300, 1255, 1185, 1135, 1030, 865,
810, 725 cmÀ1; MS (EI, 70 eV): m/z (%): 171 (35) [M+], 98 (100);
HRMS (EI, 70 eV): m/z calcd for C8H9DO232S [M+]: 171.0459; found:
171.0459.
3-Bromo-4-deuteriothiophene (4)
Following a procedure by Wagner et al.,[31] a solution of 3,4-dibro-
mothiophene (5.00 g, 20.7 mmol, 1.0 equiv) in dry THF (25 mL) was
cooled to 08C with an ice bath. iPrMgCl (13.0 mL, 1.83m (THF),
23.8 mmol, 1.15 equiv) was added over a period of 30 min and the
reaction mixture was stirred for further 1 h. A mixture of D2O
(5 mL) and D2SO4 (1 mL) was added slowly. The solution was con-
centrated, water (20 mL) was added, and the aqueous layer was ex-
tracted with diethyl ether (320 mL). The combined organic layers
were dried over MgSO4, filtered, and concentrated in vacuo. After
purification by flash column chromatography (Ø=7.0 cm, l=
15 cm, pentane), product 4 was obtained as a colorless liquid
General procedure for the determination of the relative rate
constants for Hammett analysis
A solution of Pd(tfa)2 (50.0 mmol, 0.1 equiv), Ag2O (1.00 mmol,
2.0 equiv), BQ (250 mmol, 0.5 equiv), and Cs(tfa) (500 mmol,
1.0 equiv) in a mixture of TFA and HOAc (40:60 v/v; 2.5 mL) was
stirred at 500 rpm for 5 min. The suspension was treated in an ul-
trasonic bath for 2 min. Boronic acid 2 (1.00 mmol, 2.0 equiv) was
added and stirring was continued for a further 5 min. The reaction
was started by the rapid addition of the competing thiophene sub-
strates (0.25 mmol each) and benzyl acetate (140 mmol, 0.28 equiv;
internal standard for GLC analysis) as a solution in CH2Cl2 (50 mL).
Aliquots (50 mL) of the reaction mixtures were taken every 2 min in
a 5 mL vial containing tert-butyl methyl ether (2.0 mL). The solution
was extracted immediately with an aqueous solution of sodium hy-
droxide (1.0m, 0.60 mL); the organic layer was separated and ana-
lyzed with GLC.
1
4
(3.35 g, 20.4 mmol, 99%). H NMR (500 MHz, C6D6): d=6.68 (d, J=
4
3.2 Hz, 1H), 6.51 ppm (d, J=3.2 Hz, 1H); 13C NMR (126 MHz, C6D6):
d=129.4 (t, 1J(C,D)=26.6 Hz), 126.3, 122.6, 109.8 ppm; MS (EI,
70 eV): m/z (%): 165 (100) [M(81Br)+], 163 (100) [M(79Br)+], 84 (40)
[(MÀBr)+].
Diethyl 2-(4-deuteriothiophen-3-yl)malonate (5)
Following a procedure by Gooßen et al.,[32] a Schlenk tube with
a Teflon screw cap was charged with Pd(dba)2 (92.0 mg, 160 mmol,
0.02 equiv), P(tBu)3·HBF4 (102 mg, 350 mmol, 0.044 equiv), and
K2CO3 (2.21 g, 16.0 mmol, 2.0 equiv). The reaction vessel was evacu-
ated and backfilled with argon three times. Degassed diethyl malo-
nate (4.0 mL) and 3-bromo-4-deuteriothiophene (4; 1.31 g,
8.00 mmol, 1.0 equiv) were added under an argon countercurrent
and the reaction mixture was stirred at 908C for 5 h. Water (20 mL)
was added and the resulting mixture was extracted with diethyl
ether (220 mL). The combined organic layers were dried over
MgSO4, filtered, and concentrated in vacuo. After purification by
Kugelrohr distillation, product 5 was obtained as a colorless liquid
(2.06 g, 4.49 mmol, 56%), which contained an additional 47% di-
ethyl malonate as an impurity. From the lower boiling fraction,
starting material 4 (164 mg, 1.00 mmol, 13%) was recovered after
flash column chromatography (hexane). The product was convert-
ed without further purification. 1H NMR (500 MHz, C6D6): d=7.13
(E)-Stilbene (9)
Following the general procedure for the 4-phenylation of thio-
phenes, compound 8 (57 mL, 52 mg, 0.50 mmol, 1.0 equiv) instead
of thiophene was used and the reaction mixture was stirred at
room temperature for 2.5 h. After purification by flash column
chromatography (hexane), product 9 was obtained as a colorless
1
solid (66 mg, 370 mmol, 73%) as a single isomer. H NMR (250 MHz,
CDCl3): d=7.55–7.60 (m, 4H), 7.38–7.45 (m, 4H), 7.28–7.35 (m, 2H),
7.17 ppm (s, 2H); 13C NMR (63 MHz, CDCl3): d=137.5, 128.8, 128.8,
127.7, 126.6 ppm.
Acknowledgements
This work was supported by the graduate college NanoCat
(scholarship to I.S.), the TUM Graduate School, and the Fonds
der Chemischen Industrie. T.B. conceived and directed the syn-
thetic aspects of the project, with I.S. performing all synthetic
work. S.B. devised and analyzed the kinetic studies. S.B. and
T.B. composed the manuscript.
4
4
(d, J=3.0 Hz, 1H), 6.84 (d, J=3.0 Hz, 1H), 4.71 (s, 1H), 3.85–3.93
3
(m, 4H), 0.86 ppm (t, J=7.3 Hz, 6H); 13C NMR (126 MHz, C6D6): d=
167.7, 133.0, 128.4 (t), 125.6, 124.7, 61.6, 53.8, 13.9 ppm; MS (EI,
70 eV): m/z (%): 243 (75) [M+], 170 (100), 142 (35), 125 (35), 114
(40), 98 (75), 86 (30).
Ethyl 2-(4-deuteriothiophen-3-yl)acetate [4-D1](1)
Keywords: CÀH activation · cross-coupling · heterocycles ·
kinetics · palladium
Following a procedure by Krapcho et al.,[13] a solution of crude di-
ethyl 2-(4-deuteriothiophen-3-yl)malonate (5; 2.06 g, 4.48 mmol,
1.0 equiv) and sodium hydroxide (500 mg, 8.55 mmol, 1.9 equiv) in
a mixture of water and DMSO (1/20 v/v; 10.5 mL) was heated at
1608C for 5 h. After cooling to room temperature, water (50 mL)
was added and the aqueous layer was extracted with diethyl ether
(320 mL). The combined organic layers were dried over MgSO4,
filtered, and concentrated in vacuo. After purification by flash
column chromatography (hexane/Et2O 9:1), product [4-D1]1 was
obtained as a colorless liquid (675 mg, 3.94 mmol, 88%). A purity
of 99% and a deuterium content of 99% were determined by GLC
[1] For reviews and monographs, see: a) D. Alberico, M. E. Scott, M. Laut-
Methods, Wiley-VCH, Weinheim 2009; d) X. Chen, K. M. Engle, D.-H.
Chem. Eur. J. 2015, 21, 18407 – 18416
18414
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