10.1002/ejoc.201800849
European Journal of Organic Chemistry
SHORT COMMUNICATION
the formation of the homocoupling compound. Depending on the
substituents, the propargyl radical could coordinate to the metal
complex to give the allene- (C) or the propargyl-Fe (D)
complexes, which would afford the final product through C-C
reductive elimination. Subsequent transmetalation involving
complex E would regenerate the active species. Participation of
monoalkyl-Fe complexes as productive intermediates cannot be
discarded according to the previous study.[15a] We cannot
completely rule out a mechanism involving activation of the
bromide by a non-radical mechanism. Kambe has recently
reported an Fe-catalyzed alkyl cross-coupling that seems to
follow this alternative pathway.[15a] Moreover, reduction of Fe(II)
salts by the Grignard reagent cannot be excluded, and the actual
catalytically active species, and consequently the rest of the
intermediate complexes, could have different oxidation
states.[16,17]
In conclusion, we have developed a Fe-catalyzed cross-
coupling reaction of propargyl bromides that affords either
propargyl or allene coupling compounds. The reaction is fast
enough to tolerate de presence of nitrile and ester groups, and
shows a high regioselectivity in many cases. The formation of
the possible regioisomers depends on both the kind of
substituents on the triple bond, and the steric hindrance on both
the alkyne and the propargylic carbon. The reaction seems to
involve radical species. Further studies are necessary to
ascertain the intimate details of the mechanism.
Keywords: C-C coupling • iron • Grignard reactions • radical
reactions • homogeneous catalysis
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Experimental Section
General procedure for the cross-coupling reaction:
The active catalytic species is generated first: Fe(OAc)2 (0.9 mg,
0.005 mmol, 2.5 mol%) and 1,3-dimesityl-1H-imidazol-3-ium
chloride (4.1 mg, 0.012, mmol, 6 mol%) were placed in Schlenk
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M solution of alkylmagnesium bromide (0.12 mL, 0.06 mmol, 30
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50-60 ºC for 20 min. After cooling at -78 ºC, the corresponding
propargyl bromide (0.2 mmol) was incorporated, followed by the
dropwise addition of 0.5 M solution of alkylmagnesium bromide
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TLC until completion. After reaction was completed, saturated
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was extracted with CH2Cl2 (3 × 5 mL) and the combined organic
phases were dried over MgSO4. The solvent was evaporated
under vacuum and the product was purified by column
chromatography in silica gel using mixtures of cyclohexane and
EtOAc as eluent.
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Acknowledgements
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We thank Spanish MINECO for funding (grant CTQ2016-79826-
R, a fellowship to R. S.-Y. and a Juan de la Cierva contract to M.
T. Q.) and the CAM for a postdoc fellowship to P. D.-L.
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