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dihydropyrimidine core were well tolerated in these coupling reac-
tion conditions and excellent yields of cross-coupled products
were obtained with 2-(tributylstannyl)thiophene as well as tribu-
tylstannylbenzene. Unfortunately, no desired product 9m was iso-
lated for the reaction of dihydropyrimidine 1g and vinyl tributyltin
10g.
By-products resulting from the Stille cross-coupling reaction
between bromoaryl–dihydropyrimidines 1f and organostannanes
were not observed and only the Liebeskind–Srogl adduct 9l was
isolated in good yield in accordance with the results of functional-
ized pyridinone reported by Liebeskind.19 To better understand
this selectivity between the Liebeskind–Srogl reaction and the
Stille cross-coupling reaction, compound 9l was then successfully
converted into 11a (yield: 86%) and 11b (yield: 97%) by cross-cou-
pling with 10a and 10e in the presence of PdCl2(PPh3)2 in toluene.
To our surprise, starting with the Stille cross-coupling reaction did
not afford the expected cross-coupled product. As the presence of
the thiocarbonyl function in 1f was probably a contributing factor,
we ran a test experiment with compound 1315 (the oxygenated
analog of 1f). The cross-coupled product 14 was isolated in an
excellent yield showing that the present selectivity between the
two cross-coupling reactions comes from the absence of reactivity
of the thio derivatives under Stille conditions (Scheme 3).
In summary, we have developed an optimized Liebeskind–Srogl
cross-coupling reaction to synthesize potentially biologically ac-
tive 2-aryl-1,4-dihydropyrimidines in good to excellent yields with
various heteroarylstannanes.
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Acknowledgments
12. Sehon, C. A.; Wang, G. Z.; Viet, A. Q.; Goodman, K. B.; Dowdell, S. E.; Elkins, P. A.;
Semus, S. F.; Evans, C.; Jolivette, L. J.; Kirkpatrick, R. B.; Dul, E.; Khandekar, S. S.;
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We thank the Foundation of French–China Science and its
Application (FFCSA) and the China Scholars Council (CSC) for finan-
cial support.
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Supplementary data
Supplementary data associated with this article can be found, in
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Keromnes, A.; Lebret, B.; Guillaumet, G. Synthesis 2004, 2893–2899.
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18. There were two isomers (2:1), 1,4-dihydropyrimidine and 3,4-
dihydropyrimidine. We therefore added one drop of TFA in DMSO or used
their HCl salt to fix one isomer to obtain satisfactory, NMR spectra (see
Supplementary data).
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