10.1002/anie.202014141
Angewandte Chemie International Edition
RESEARCH ARTICLE
Opportunities to increase the rate of these Stille couplings in water
using the corresponding trimethylstannane analogs, in place of
the far more typical tri-n-butylstannanes, led to the expected
results. Thus, as shown in Scheme 6, in all cases examined, the
aryltrimethylstannane coupling partner gave greater levels of
conversion for the times allotted, thereby leading to higher
chemical yields.
this technology at scale was also shown via synthesis of the
pharmaceutical intermediate OSU6255. Pre-catalyst P9, likewise,
could be applied to efficient stannylations of aryl halides. Finally,
recycling of the catalyst and surfactant was illustrated via a 2-step
sequence involving initial stannylation followed by Stille coupling
in the same pot without additional catalyst. Further advances
using the many attributes of chemistry in water will be reported in
due course.
1000 ppm P9
1000 ppm PPh3
CuI (5 mol %)
Br/I
R3Sn
2 wt % Brij-30/H2O (0.5 M)
TBAC (10 mol %)
KF (3 equiv), 55 o
C
Acknowledgements
Financial support by PHT International (postdoctoral fellowship to
B.S.T.), NSF (CHE 18-56406), and Novartis is warmly
acknowledged with thanks.
N
O
NC
NO2
22 h
CF3
O
24 h
24 h
10 h
Keywords: cross coupling • Stille couplings • organostannanes
26, 51% (R = Bu)
47, 43% (R = Bu)
48, 70% (R = Bu)
48, 85% (R = Bu)
88% (R = Me)
80% (R = Me)
81% (R = Me)
93% (R = Me)
• green chemistry • parts per million catalysis
Scheme 6. Comparison reactions of trimethyl- vs. tri-n-butyl-stannanes.
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