Journal of the American Chemical Society
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Miyaura and Negishi coupling,5b,10 it contrasts the more facile
ASSOCIATED CONTENT
Supporting Information
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nature of oxidative addition into electron-rich benzamide 3b
versus electron-deficient benzamide 3k due to the increased
amidic resonance that would be expected for 3k versus 3b.11
In addition, this result suggests that the ratio of products ob-
served is not determined by the relative rates of oxidative
addition of 3k and 3b. Competition experiments between the
pinacol ester of 4-tolylboronic acid with the pinacol esters of
2-tolylboronic acid or 4-(trifluoromethyl)pheylboronic acid
formed ketones 2p and 2c in an 8.3:1 ratio and ketones 2j
and 2c in a 10.5:1 ratio. The observation that ketones de-
rived from reactions with sterically hindered and electron-
deficient arylboron nucleophiles are favored suggests that
transmetalation is fast relative to reductive elimination and
the ratio of products is determined by the relative rates of
either reductive elimination or migratory insertion into the Ni-
C(acyl) bond of complex III. Given that a nearly equimolar
ratio of 4k and 4b would be expected from the competition
between 3k and 3b if reductive elimination was turnover-lim-
iting, we propose that migratory insertion of the alkene into
the Ni-C(acyl) bond is the elementary step critical to deter-
mining product ratios.
The Supporting Information is available free of charge on the
ACS Publications website.
Experimental procedures, characterization data, and copies
of NMR spectra for new compounds (PDF)
AUTHOR INFORMATION
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Corresponding Author
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Author Contributions
†J.A.W. Jr. and K.L.V. contributed equally to this work.
ACKNOWLEDGMENT
We thank the National Science Foundation (CHE-1352080)
for supporting this work.
REFERENCES
Scheme 5. Competition Experiments between Substi-
tuted Benzamides or Arylboronic Acid Pinacol Esters
(1) (a) Dreis, A. M.; Douglas, C. J. J. Am. Chem. Soc. 2009, 131,
412. (b) Wentzel, M. T.; Reddy, V. J.; Hyster, T. K.; Douglas, C. J.
Angew. Chem., Int. Ed. 2009, 48, 6121. (c) Rathbun, C. M.; Johnson,
J. B. J. Am. Chem. Soc. 2011, 133, 2031. (d) Lutz, J. P.; Rathbun,
C. M.; Stevenson, S. M.; Powell, B. M.; Boman, T. S.; Baxter, C. E.;
Zona, J. M.; Johnson, J. B. J. Am. Chem. Soc. 2012, 134, 715. (e)
Dreis, A. M.; Douglas, C. J. Top. Curr. Chem. 2014, 346, 85.
(2) (a) Liu, L.; Ishida, N.; Murakami, M. Angew. Chem., Int. Ed.
2012, 51, 2485. (b) Xu, T.; Dong, G. Angew. Chem., Int. Ed. 2012,
51, 7567. (c) Xu, T.; Ko, H. M.; Savage, N. A.; Dong, G. J. Am. Chem.
Soc. 2012, 134, 20005. (d) Souillart, L.; Parker, E.; Cramer, N. An-
gew. Chem., Int. Ed. 2014, 53, 3001. (e) Xu, T.; Dong, G. Angew.
Chem., Int. Ed. 2014, 53, 10733. (f) Lu, G.; Fang, C.; Xu, T.; Dong,
G.; Liu, P. J. Am. Chem. Soc. 2015, 137, 8274. (g) Souillart, L.;
Cramer, N. Chimia 2015, 69, 187.
(3) For recent examples of carbonylative approaches to formal
alkene carboacylation, see: (a) Liu, C.; Widenhoefer, R. A. J. Am.
Chem. Soc. 2004, 126, 10250. (b) Fusano, A.; Sumino, S.; Fuku-
yama, T.; Ryu, I. Org. Lett. 2011, 13, 2114. (c) Seashore-Ludlow, B.;
Danielsson, J.; Somfai, P. Adv. Synth. Catal. 2012, 354, 205. (d)
McMahon, C. M.; Renn, M. S.; Alexanian, E. J. Org. Lett. 2016, 18,
4148.
(4) For other approaches to formal alkene carboacylation, see: (a)
Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Organomet. Chem.
2002, 648, 297. (b) Yamane, M.; Kubota, Y.; Narasaka, K. Bull.
Chem. Soc. Jpn. 2005, 78, 331. (c) Ouyang, X.-H.; Song, R.-J.; Li,
J.-H. Eur. J. Org. Chem. 2014, 3395. (d) Ouyang, X.-H.; Song, R.-J.;
Li, Y.; Liu, B.; Li, J.-H. J. Org. Chem. 2014, 79, 4582. (e) Park, J.-W.;
Kou, K. G. M.; Kim, D. K.; Dong, V. M. Chem. Sci. 2015, 6, 4479.
(5) For recent examples, see: (a) Li, X.; Zou, G. Chem. Commun.
(Cambridge, U. K.) 2015, 51, 5089. (b) Meng, G. R.; Szostak, M. Org.
Lett. 2015, 17, 4364. (c) Weires, N. A.; Baker, E. L.; Garg, N. K. Nat.
Chem. 2016, 8, 75. (d) Liu, C. W.; Meng, G. R.; Liu, Y. M.; Liu, R. Z.;
Lalancette, R.; Szostak, R.; Szostak, M. Org. Lett. 2016, 18, 4194.
(e) Meng, G. R.; Shi, S. C.; Szostak, M. ACS Catal. 2016, 6, 7335. (f)
Meng, G. R.; Szostak, M. Org. Biomol. Chem. 2016, 14, 5690. (g)
Lei, P.; Meng, G. G.; Szostak, M. ACS Catal. 2017, 7, 1960. (h) Liu,
C. W.; Liu, Y. M.; Liu, R. Z.; Lalancette, R.; Szostak, R.; Szostak, M.
Org. Lett. 2017, 19, 1434. For decarbonylative coupling of ben-
zamides with arylboronic acids, see: (i) Shi, S.; Meng. G.; Szostak,
M. Angew. Chem. Int. Ed. 2016, 55, 6959. For recent reviews, see:
(j) Meng, G. R.; Shi, S. C.; Szostak, M. Synlett 2016, 27, 2530. (k)
Dander, J. E.; Garg, N. K. ACS Catal. 2017, 7, 1413. (l) Liu, C.; Szos-
tak, M. Chem. Eur. J. 2017, 23, 7157.
O
4k
Ni(cod)2 (10 mol %)
SIPr (10 mol %)
PhBpin (5 equiv)
3k (1 equiv)
+
Ph
4b
Ph
F3C
O
+
K3PO4 (2 equiv)
H2O (2 equiv)
THF (1 M), 60 °C, 12 h
3b (1 equiv)
4k:4b = 6.8:1
O
1a
(1 equiv)
+
Ni(cod)2 (10 mol %)
SIPr (10 mol %)
Bpin
Bpin
O
+
2p
2c
K3PO4 (2 equiv)
H2O (2 equiv)
THF (1 M), 60 °C, 12 h
+
(5 equiv) (5 equiv)
2p:2c = 8.3:1
O
1a
+
(1 equiv)
Ni(cod)2 (20 mol %)
Bpin
SIPr (20 mol %)
Bpin
+
O
2j
K3PO4 (2 equiv)
H2O (2 equiv)
THF (0.5 M), 60 °C, 12 h
+
CF3
2c
CF3
(5 equiv) (5 equiv)
2j:2c = 10.5:1
In summary, we have developed the first nickel-catalyzed
alkene carboacylation reactions initiated by activation of am-
ide C-N bonds. These processes enable coupling of a vari-
ety of ortho-allylbenzamides and arylboronic acid pinacol
esters to form two new C-C bonds and the indanone prod-
ucts in up to 99% yield. Moreover, the development of this
approach to alkene carboacylation bypasses challenges as-
sociated with related alkene carboacylation reactions that
rely on C-C bond activation and further demonstrates the
utility of amides as powerful building blocks in organic syn-
thesis. Studies are ongoing in our laboratory to further lever-
age the synthetic potential of this transformation and to gain
additional mechanistic understanding of the nickel-cata-
lyzed alkene carboacylation reaction.
(6) Medina, J. M.; Moreno, J.; Racine, S.; Du, S.; Garg, N. K. An-
gew. Chem., Int. Ed. 2017, 56, 6567.
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