10.1002/ejoc.201701463
European Journal of Organic Chemistry
COMMUNICATION
and 0.02 mmol of tricyclohexylphosphine. A vial was transferred to a
preaheated oil bath (110°C). After 24 h reaction mixture was cooled and
1 mmol (1 eq.) of second coupling reagent (aryl halide), 0.01 mmol
palladium acetate, 0.02 mmol of tricyclohexylphosphine and 1.5 mmol
(1.5 eq.) of anhydrous cesium fluoride were added to the reaction mixture.
A vial was transferred to a preaheated oil bath (110°C). After 24 h
reaction mixture was cooled, dissolved in CH2Cl2-H2O mixture (1:1),
organic phase separated, solvent evaporated in vacuum and the product
isolated by flash chromatography on a silica gel by elution with hexane-
CH2Cl2 mixture.
accessible and relatively cheap Pd(OAc)2/PCy3 (1 mol%). The
scope of the coupling partners is wide: a variety of functionalized
(het)aryl halides (including challenging aryl chlorides), bearing
acceptor, donor, as well as sterically demanding substituents,
challenging substituents, not tolerant to lithium or magnesium
reagents, can be stannylated and/or coupled in high efficiency. 9
examples of aryl stannanes were synthesized and characterized
for the first time.
The developed protocols have a number of advantages: (i) no
solvent is used, (ii) reaction is performed under aerobic
conditions, (iii) low catalyst loading, (iv) available base CsF, (v)
activation of reaction by conventional heating (no milling,
sonication, etc. needed). Thus, we have developed a versatile,
robust, highly active catalytic system for the stannylation, Stille
and SSC reactions. Reaction protocols can be scaled-up with no
significant loss in efficiency.
Acknowledgements
The reported study was supported by the Russian Science
Foundation (RSF) grant number 17-13-01076. L.I.M. would like
to acknowledge the support by the Ministry of Education and
Science of the Russian Federation (the Agreement number
02.a03.21.0008).
The absence of a solvent, the use of conventional heating and
the elimination of isolation procedures of aryl stannanes make
this protocol not only simple and step economical but also highly
efficient for the synthesis of the unsymmetrical biaryls via SSC
one-pot two-step procedure.
Keywords: cross-coupling reaction • stannylation • Stille
coupling • palladium • solvent-free reactions
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Experimental Section
General procedure A for the preparation of aryl stannanes: a screw-
cap vial equipped with a magnetic stir bar was charged with 1 mmol (1
eq.) of aryl halide, 1.1 mmol (1.1 eq.) of hexa-n-butylditin, 0.01 mmol of
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transferred to a preaheated oil bath (110°C). After 24 h reaction mixture
was cooled, dissolved in CH2Cl2-H2O mixture (1:1), organic phase
separated, solvent evaporated in vacuum and the product isolated by
flash chromatography on a silica gel by elution with hexane-CH2Cl2
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bottom 50 ml flask equipped with a reflux condenser with argon inlet and
a magnetic stir bar was charged with 20 mmol (3.14 g) of bromobenzene,
22 mmol (12.76 g) of hexa-n-butylditin, 0.2 mmol (45 mg) of palladium
acetate and 0.4 mmol (112 mg) of tricyclohexylphosphine. The reaction
mixture was degassed with 3 Freeze-Pump-Thaw cycles. The flask was
transferred to a preheated oil bath (110°C) and stirred for 24 h. The
reaction mixture was evacuated until all volatiles were distilled off, then
residue was distilled out into liquid nitrogen trap to give
bromotributylstannane (b.p. 72 - 77 °C/0.1 mm Hg) and 7.12 g (yield:
97 %) of the pure product (b.p. 115 - 120°C/0.1 mm Hg).
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General procedure
B for the solvent-free Stille cross-coupling
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h reaction mixture was cooled, dissolved in CH2Cl2-H2O mixture (1:1),
organic phase separated, solvent evaporated in vacuum and the product
isolated by flash chromatography on a silica gel by elution with hexane-
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General procedure
C for the one-pot stannylation-Stille cross-
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coupling of aryl halides: a screw-cap vial equipped with a magnetic stir
bar was charged with 1 mmol (1 eq.) of first coupling reagent (aryl halide),
1.03 mmol (1.03 eq.) of hexa-n-butylditin, 0.01 mmol palladium acetate
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