reSeArCH Letter
O
R
(HO)2B
R
(2 equiv.)
OH
O
O
S
10 mol % Ni(cod)2
20 mol % PPh2Me
O
TFFH (1 equiv.)
S
N
N
O
Proton Sponge (1 equiv.)
THF, RT, 15–30 min
O
P
THF, 100 °C, 16 h
F
P
Isolated or in situ
Activation
Cross-coupling
R
P
CO2H
40
Probenecid analogues
Probenecid
a
F
OMe
O
P
P
P
P
O
P
O
41, 80% (in situ 82%)
42, 75%
43, 89%
44, 92% (in situ 74%)
45, 69%
P
P
P
P
OMe
46, 73%
47, 56%
48, 42%
49, 51%
b
O
N
CF3
P
N
N
P
P
P
O
S
P
O
P
P
S
Boc
50, 58%
51, 82% (in situ 79%)
52, 71%
53, 83%
54, 43%, 60 °C (58%, b.r.s.m.)
55, 77%
56, 93%
F
F
F
F
CF3
F
OMe
F
F
F
O
F
F
F
F
P
P
P
P
P
P
F
F
F
F
F
57, 67%a
58, 86%
61, 85%
59, 72% (in situ 69%)
60, 60% (in situ 66%)
62, 75% (in situ 72%)
F
F
c
O
F
O
F
Air stable,
commercial
B(OH)2
F
F
O
Me
Method A or B
F
PPh2Me
F
+
O
S
THF, 100 °C, 16 h
N
Ni Cl
S
O
N
F
O
O
PPh2Me
Cross-coupling
61
40
64
A: 93%19F NMR, 85% isolated
B: 77%19F NMR, 66% isolated
63
Fig. 4 | Scope of the nickel-catalysed decarbonylative Suzuki–Miyaura
coupling with various organoboron reagents. a, (Hetero)aryl, alkenyl,
and alkyl boronic acids. b, Organoboron reagents that undergo facile
protodeboronation. b.r.s.m., based on recovered starting material. c, Use
of a commercial, air-stable precatalyst 63. Method A involves standard
conditions and is operated in a dry box. Method B: 10 mol% 63, 10 mol%
CsF, all catalysts and reagents are handled on the benchtop. P (in blue),
probenecid aryl fragment; Boc, tert-butoxycarbonyl. aIsolated product
contains inseparable ketone by-product (5%). For details on reaction
conditions and for examples of organoboron reagents that did not undergo
high yielding decarbonylative coupling, see Supplementary Information.
8. Robbins, D. W. & Hartwig, J. F. A C–H borylation approach to Suzuki–Miyaura
coupling of typically unstable 2-heteroaryl and polyfuorophenyl boronates.
Org. Lett. 14, 4266–4269 (2012).
9. Bulfeld, D. & Huber, S. M. Synthesis of polyfuorinated biphenyls; pushing the
boundaries of Suzuki–Miyaura cross coupling with electron-poor substrates. J.
Org. Chem. 82, 13188–13203 (2017).
10. Kinzel, T., Zhang, Y. & Buchwald, S. L. A new palladium precatalyst allows for the
fast Suzuki–Miyaura coupling reactions of unstable polyfuorophenyl and
2-heteroaryl boronic acids. J. Am. Chem. Soc. 132, 14073–14075 (2010).
11. Chen, L., Francis, H. & Carrow, B. P. An “on-cycle” precatalyst enables
room-temperature polyfuoroarylation using sensitive boronic acids. ACS Catal.
8, 2989–2994 (2018).
18. Gooßen, L. J., Deng, G. & Levy, L. M. Synthesis of biaryls via catalytic
decarboxylative coupling. Science 313, 662–664 (2006).
19. Zuo, Z. et al. Merging photoredox with nickel catalysis: coupling of α-carbonyl
sp3-carbons with aryl halides. Science 345, 437–440 (2014).
20. Wang, J. et al. Nickel-catalyzed cross-coupling of redox active esters with
boronic acids. Angew. Chem. Int. Ed. 55, 9676–9679 (2016).
21. Edwards, J. T. et al. Decarboxylative alkenylation. Nature 545, 213–218 (2017).
22. Fawcett, A. et al. Photoinduced decarboxylative borylation of carboxylic acids.
Science 357, 283–286 (2017).
23. Carrow, B. P. & Hartwig, J. F. Distinguishing between pathways for
transmetalation in Suzuki–Miyaura reactions. J. Am. Chem. Soc. 133,
2116–2119 (2011).
12. Chen, L., Sanchez, D. R., Zhang, B. & Carrow, B. P. “Cationic” Suzuki–Miyaura
coupling with acutely base-sensitive boronic acids. J. Am. Chem. Soc. 139,
12418–12421 (2017).
13. Ohashi, M., Saijo, H., Shibata, M. & Ogoshi, S. Palladium-catalyzed base-free
Suzuki–Miyaura coupling reactions of fuorinated alkenes and arenes via a
palladium fuoride key intermediate. Eur. J. Org. Chem. 443–447 (2013).
14. Graham, T. J. A. & Doyle, A. G. Nickel-catalyzed cross-coupling of chromene
acetals and boronic acids. Org. Lett. 14, 1616–1619 (2012).
15. Zhang, Y. & Rovis, T. A unique catalyst efects the rapid room-temperature
cross-coupling of organozinc reagents with carboxylic acid fuorides, chlorides,
anhydrides, and thioesters. J. Am. Chem. Soc. 126, 15964–15965 (2004).
16. Keaveney, S. T. & Schoenebeck, F. Palladium-catalyzed decarbonylative
trifuoromethylation of acid fuorides. Angew. Chem. Int. Ed. 57, 4073–4077
(2018).
17. Ogiwara, Y., Sakurai, Y., Hattori, H. & Sakai, N. Palladium-catalyzed reductive
conversion of acyl fuorides via ligand-controlled decarbonylation. Org. Lett. 20,
4204–4208 (2018).
24. Amatore, C., Jutand, A. & Le Duc, G. The triple role of fuoride ions in palladium-
catalyzed Suzuki–Miyaura reactions: unprecedented transmetalation from
[ArPdFL2] complexes. Angew. Chem. Int. Ed. 51, 1379–1382 (2012).
25. Thomas, A. A. & Denmark, S. E. Pre-transmetalation intermediates in the
Suzuki–Miyaura reaction revealed: the missing link. Science 352, 329–332
(2016).
26. Muto, K., Yamaguchi, J., Musaev, D. G. & Itami, K. Decarbonylative organoboron
cross-coupling of esters by nickel catalysis. Nat. Commun. 6, 7508 (2015).
27. Shi, S., Meng, G. & Szostak, M. Synthesis of biaryls through nickel-catalyzed
Suzuki–Miyaura coupling of amides by carbon–nitrogen bond cleavage. Angew.
Chem. Int. Ed. 55, 6959–6963 (2016).
28. Guo, L. & Rueping, M. Decarbonylative cross-couplings: nickel catalyzed
functional group interconversion strategies for the construction of complex
organic molecules. Acc. Chem. Res. 51, 1185–1195 (2018).
29. Masson-Makdissi, J., Vandavasi, J. K. & Newman, S. G. Switchable selectivity in
the Pd-catalyzed alkylative cross-coupling of esters. Org. Lett. 20, 4094–4098
(2018).
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