Communication
Notes
Based on these experiments and previously proposed reac-
tion mechanism, we depicted the plausible reaction mechanism
(Scheme 4). Reduction of the NiII with Zn0 forms Ni0, and oxid-
ative addition of aryl iodide forms NiII intermediate I. Generated
I interacts with aldehyde and acid (H–X) to form a reactive inter-
mediate II. 1,2-Migratory insertion of the aryl group into the
aldehyde could form an alkoxy–NiII product III. Although we
have observed a trace amount of formation of corresponding
ketone side product which is generated by ꢀ-elimination of alk-
oxy–NiII intermediate, a route for the direct release the product
from II cannot be ruled out. Finally, alkoxy exchange reaction
of III and reduction of NiII completes the catalytic cycle.
The authors declare no competing financial interest.
Acknowledgments
The work was financially supported by the Ogawa Science
Foundation (EY) and Grant-in-Aid for Young Scientists Grant
Number 18K14871 (EY).
Keywords: Reductive arylation · Ni catalysis · Grignard
reaction · Carbonyl arylation
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Scheme 4. Plausible reaction mechanism.
Conclusions
In conclusion, we have developed a reductive arylation reaction
for aldehydes, catalyzed using nickel complexes. This reaction
shows a broad functional group tolerance, including ester, ket-
one, cyano, halide, heteroarene, amide, and benzyl alcohol
groups. In addition, we achieved preliminary results regarding
the enantioselective reductive arylation of aldehydes using
nickel/chiral bisoxazoline ligands. Further studies related to the
reaction mechanism and potential applications are currently
progressing in our laboratory.
Experimental Section
General Procedure for Synthesis of 3: Screw capped test tube
(16.5 cm × 1.5 cm) containing a mixture of aldehyde 1 (0.3 mmol),
iodebenzene
1 (2.0 equiv., 0.6 mmol), NiCl2(bpy) (4.3 mg,
0.05 equiv., 0.015 mmol), (PhO)2PO2H (112.5 mg, 1.5 equiv.,
0.45 mmol), NaI (11.2 mg, 0.25 equiv., 0.075 mmol), Zn0 (58.8 mg,
3.0 equiv., 0.9 mmol), and HNiPr2 (44.2 μL, 1.0 equiv., 0.3 mmol) in
dried n-hexane (1.0 mL) was degassed via FPT cycling for three
times and backfilled with Ar. The resulting solution was stirred at
95 °C, 7 h (caution; blast shield was set around reaction vessel). The
solution was filtered through celite, washing with chloroform sev-
eral times, and concentrated in vacuo. The resulting mixture was
purified by flash column chromatography on silica gel (n-hexane/
EtOAc) to give 3.
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