E
M. J. Geier et al.
Letter
Synlett
1) i-PrMgCl, THF, –15 °C
2) ZnCl2, MeTHF, –15 °C
O
N
O
N
Ar
3) ArBr
4) t-BuXPhos Pd G3, 65 °C
O
O
N
O
N
O
N
N
F3C
EtO2C
O
O
S
N
O
H
2: 75%
6: 75%
7: 87%
N
O
S
O
O
O
N
O
NC
O
N
8: 73%
9: 93%
10: 84%
13: 70%
O
N
O
N
O
N
F
11: 77%
12: 61%
O
N
O
N
O
14: 42%
15: 51%
Scheme 4 Substrate scope of oxazole Negishi coupling. Conditions: A stock solution was prepared by addition of i-PrMgCl to oxazole in THF at –15 °C,
followed by addition of a solution of ZnCl2 in MeTHF, and then warming the solution to 22 °C. A portion of this stock solution was dosed to reaction
vessels with the substrate (2.5 mmol), followed by addition of t-BuXPhos Pd G3 (5 mol%), and warmed to 65 °C for 18 hours under nitrogen. Each
reaction contained substrate (2.5 mmol), oxazole (3.0 equiv), t-BuXPhos Pd G3 (5 mol%), i-PrMgCl (2 M in THF, 3.2 equiv), ZnCl2 (6.0 equiv), THF (7 mL),
and MeTHF (6 mL).
References and Notes
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2-{5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,4-
dihydrothieno[2,3-d]pyrimidin-3(2H)-yl}propanoate (2)
A stock solution was prepared by addition of i-PrMgCl (60 mL,
120 mmol) to oxazole (7.3 mL, 112 mmol) in THF (120 mL) at
–15 °C, followed by addition of a solution of ZnCl2 (30.5 g, 224
mmol) in MeTHF (105 mL) and warming to 22 °C. To a reaction
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© 2019. Thieme. All rights reserved. — Synlett 2019, 30, A–F