E.M. Woerly et al. / Tetrahedron 67 (2011) 4333e4343
4339
1H NMR (400 MHz, acetone-d6)
d
7.46 (m, 3H), 7.34 (t, J¼7.5 Hz,
acetone solution, and purified via flash chromatography on Florisil
(Et2O/acetone 100:0/2:1) to afford MIDA boronate 9 as a pale
yellow solid (42.4 mg, 86%).
2H), 7.25 (m, 1H), 6.87 (app t, J¼12.0 Hz, 1H), 6.62 (d, J¼15.5 Hz,1H),
5.52 (d, J¼14.0 Hz, 1H), 4.29 (d, J¼17.0 Hz, 2H), 4.09 (d, J¼17.0 Hz,
2H), 3.07 (s, 3H). 13C NMR (100 MHz, acetone-d6)
d
169.0, 144.3,
1H NMR (500 MHz, CD3CN)
d
7.78 (dd, J¼11.5, 15.0 Hz, 1H), 6.81
138.2, 135.6, 129.4, 128.7, 128.5, 127.3, 62.3, 42.3. HRMS (ESIþ) cal-
(app t, J¼12.5 Hz, 1H), 5.94 (d, J¼15.0 Hz, 1H), 5.85 (d, J¼14.0 Hz,
1H), 3.98 (d, J¼17.0 Hz, 2H), 3.83 (d, J¼17.0 Hz, 2H), 3.69 (s, 3H), 2.82
culated for C15H17BNO4 (MþH)þ: 286.1251. Found: 286.1253.
(s, 3H). 13C NMR (125 MHz, CD3CN)
d 169.0,168.0,143.5,141.4,124.5,
62.6, 52.1, 47.6. HRMS (ESIþ) calculated for C11H15BNO6 (MþH)þ:
4.6. General procedure: Stille coupling
268.0992. Found: 268.0991.
In a glovebox, to a 7 mL vial equipped with a stir bar and charged
with (Z)-Br-1 or (E)-Br-1 (0.2 mmol) and vinyl stannane 6 or 1-
triethylgermanium-2-tributyltin ethylene (Z)-20 or (E)-20
(0.22 mmol) were added Pd2(dba)3 (0.01 mmol) and Ph3As
(0.02 mmol). The vial was sealed with a PTFE-lined septum screw-
cap and removed from the glovebox. At 0 ꢀC, under a positive
pressure of Ar, THF (0.5 mL) and DMF (1.5 mL) were added se-
quentially via syringe. The resulting mixture was stirred in a sub-
dued light environment at 0 ꢀC for 2 h and then slowly warmed to
23 ꢀC and stirred for an additional 8e18 h at 23 ꢀC. The reaction
mixture was poured into brine (5.0 mL) and extracted with EtOAc
(2ꢁ15 mL). The combined organic phases were dried over MgSO4,
concentrated in vacuo, dry loaded onto Celite from an acetone so-
lution, and purified via flash chromatography on silica gel or Florisil
to afford the desired compound.
4.9. MIDA boronate 11
In a glovebox, to a 7 mL vial equipped with a stir bar and charged
with (Z)-Br-1 (62.8 mg, 0.24 mmol) were added CuI (2.6 mg,
0.014 mmol) and PdCl2(PPh3)2 (19.5 mg, 0.028 mmol). The vial was
sealed with a PTFE-lined septum screw-cap and removed from the
glovebox. Under a positive pressure of Ar, THF (1.2 mL), TMS-
acetylene 10 (0.050 mL, 0.36 mmol), and Et3N (0.10 mL,
0.72 mmol) were sequentially added via syringe. The reaction was
stirred at 23 ꢀC for 4 h. The crude reaction was transferred to
a separatory funnel containing brine (10 mL) and extracted with
EtOAc (2ꢁ15 mL). The combined organic extracts were dried over
Na2SO4, filtered, dry loaded onto Celite and purified via flash
chromatography on Florisil (Et2O/EtOAc 3:1/2:1/1:1) to afford
MIDA boronate 11 as a yellow solid (54 mg, 80%). Colorless crystals
could be obtained by recrystallization from Et2O (42 mg, 63%).
4.7. MIDA boronate 7
The general Stille coupling procedure was followed using (Z)-Br-
1 (39 mg, 0.15 mmol), vinyl stannane 6 (53 mg, 0.17 mmol),
Pd2(dba)3 (7.0 mg, 0.01 mmol), Ph3As (4.6 mg, 0.02 mmol), THF
(0.5 mL), and DMF (1.5 mL). The resulting mixture was stirred at
1H NMR (500 MHz, CDCl3)
J¼14.5 Hz, 1H), 4.00 (d, J¼16.5 Hz, 2H), 3.87 (d, J¼16.5 Hz, 2H), 2.91
d
6.27 (d, J¼14.5 Hz, 1H), 6.05 (d,
(s, 3H), 0.17 (s, 9H). 13C NMR (125 MHz, CDCl3)
d 167.7, 124.2, 103.8,
ꢀC for 2 h and then slowly warmed to 23 ꢀC and stirred for an
101.1, 63.0, 47.4, ꢂ0.38. HRMS (ESIþ) calculated for C12H19BNO4Si
0
additional 18 h at 23 ꢀC. Purification via flash chromatography on
Florisil (EtOAc/petroleum ether 1:1/EtOAc/EtOAc/MeCN 9:1)
afforded 7 as a foam (25 mg, 79%).
(MþH)þ: 280.1176. Found: 280.1170.
1H NMR (500 MHz, CD3CN)
d
6.85 (ddd, J¼17.0, 10.0, 1.0 Hz, 1H),
6.70 (app t, J¼11.0 Hz, 1H), 5.39 (d, J¼13.5 Hz, 1H), 5.27 (dd, J¼17.0,
2.0 Hz, 1H), 5.23 (ddd, J¼10.0, 2.0, 1.0 Hz, 1H), 3.95 (d, J¼17.0 Hz,
2H), 3.79 (d, J¼17.0 Hz, 2H), 2.79 (s, 3H). 13C NMR (125 MHz, CD3CN)
d
169.1, 145.2, 136.7, 120.6, 62.4, 47.5. HRMS (ESIþ) calculated for
C9H13BNO4 (MþH)þ: 210.0938. Found: 210.0940. IR (thin film,
cmꢂ1) 3006, 2954, 2852, 1767, 1577, 1458, 1288, 1022, 997, 866.
4.10. MIDA boronate 13
4.10.1. (2-Methyl-1-propenyl)zinc bromide solution 12 was prepared
as follows. A 4 mL vial equipped with a magnetic stir bar was
charged with zinc bromide (68 mg, 0.31 mmol), flushed with Ar and
sealed with a PTFE-lined septum screw-cap. THF (1.0 mL) was
added and the solution was stirred at 0 ꢀC for 10 min. 2-Methyl-1-
propenyl magnesium bromide (0.6 mL, 0.30 mmol, 0.5 M in THF)
was added and the solution was stirred at 0 ꢀC for 30 min.
4.8. MIDA boronate 9
4.10.2. The freshly prepared solution of 12 was used in the following
reaction. In a glovebox, to a 7 mL vial equipped with a magnetic stir
bar and charged with (Z)-Br-1 (39 mg, 0.15 mmol) were added
Pd(OAc)2 (2 mg, 0.01 mmol) and SPhos (6 mg, 0.02 mmol). The vial
was sealed with a PTFE-lined septum screw-cap and removed from
the glovebox. The resulting slurry was stirred for 30 min at 23 ꢀC
and was then cooled to 0 ꢀC. The freshly prepared solution of 12 was
added dropwise to the reaction vial. The resulting mixture was
stirred in a subdued light environment at 0 ꢀC for 2 h. The reaction
In a glovebox, to a 7 mL vial equipped with a stir bar and charged
with MIDA boronate (Z)-Br-1 (48.3 mg, 0.18 mmol) was added
Pd(OAc)2 (3.4 mg, 0.05 mmol), a solution of methyl acrylate 8 (0.4 M
in DMF, 1.0 mL), and a solution of freshly distilled Et3N (0.4 M in
DMF, 1.0 mL). The vial was sealed with a cap and removed from the
glovebox. The solution was stirred in a subdued light environment
at 23 ꢀC for 46.5 h. The reaction mixture was filtered through a pad
of Celite, concentrated in vacuo, dry loaded onto Celite from an