Acylation of aryl halides and α-bromo acetates with aldehydes enabled by nickel/tbadt cocatalysis

Article abstract of DOI:10.1021/acs.orglett.0c01121

In this protocol aryl halides and α-bromo acetates are efficiently cross-coupled with an array of (hetero)aromatic and aliphatic aldehydes under the cooperative catalysis of nickel and tetrabutylammonium decatungstate as a hydrogen-atom-transfer photocatalyst. This method provides a concise approach to a variety of ketones with high compatibility of various functional groups.

Full text of DOI:10.1021/acs.orglett.0c01121

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Letter
Acylation of Aryl Halides and α‑Bromo Acetates with Aldehydes
Enabled by Nickel/TBADT Cocatalysis
Pei Fan, Chang Zhang, Linchuan Zhang, and Chuan Wang*
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ABSTRACT: In this protocol aryl halides and α-bromo acetates
are efficiently cross-coupled with an array of (hetero)aromatic and
aliphatic aldehydes under the cooperative catalysis of nickel and
tetrabutylammonium decatungstate as a hydrogen-atom-transfer
photocatalyst. This method provides a concise approach to a
variety of ketones with high compatibility of various functional groups.
Scheme 1. (A) TBADT-Catalyzed Reactions Using
Aldehydes; (B) Ni/TBADT-Cocatalyzed Acylation of Aryl
or Alkyl Halides
ecause aldehydes are abundant, inexpensive, and easily
accessible precursors, the preparation of ketones in one
B
single step using aldehydes as acyl source is a concise and
appealing method. Therefore, many organic reactions have
been established following this concept, such as Benzoin
reaction,1 Stetter reaction,2 and transition-metal catalyzed
hydroacylation of alkenes or alkynes.3 Furthermore, cross-
couplings of aldehydes with aryl (pseudo)halides4 or organo-
metallics5 were also achieved under the catalysis of Pd, Ni, Ru,
or Rh. Generally, these reactions required high reaction
temperature. In contrast, a Ni/photo cocatalytic acylation of
aryl and alkyl halides with aldehydes under mild reaction
conditions was developed by MacMillan and his co-worker.6
However, the use of an expensive noble-metal photocatalyst is
̈
less desirable. Very recently, Konig et al. reported that the
photochemical Ni-catalyzed acylation of aryl bromides still
proceeded smoothly even in the absence of an external
photocatalyst.7 The major disadvantage of this method is that
the substrate scope is limited to aromatic aldehydes.
Tetrabutylammonium decatungstate (TBADT) is a well-
known hydrogen-atom-transfer (HAT) photocatalyst, which is
able to promote numerous reactions involving C−H bond
activation of a radical type.8,9 Notably, TBADT can be
prepared in one single step from the inexpensive precursor.10
The pioneering work of Fagnoni et al. disclosed that acyl
radicals can be generated from aldehydes via homolytic acyl
C−H bond cleavage under the photocatalysis of TBADT,9c
and this elementary reaction has been engaged as a key step in
hydroacylation of alkenes9c,e,g,q and imines9p as well as
deuteration9r of aldehydes (Scheme 1A). On the other side,
Ni(0) is able to undergo oxidative addition with aryl or alkyl
halides, to afford a Ni(II)-species. We envisage that the
generated Ni(II) intermediate could be further oxidized by an
acyl radical in a Ni/TBADT-cocatalyzed reaction,11 to provide
a Ni(III) species,6 which upon reductive elimination results in
a variety of ketones (Scheme 1B).
as standard substrates for optimizing the reaction conditions
(Table 1). Systematic screening of various parameters
including solvents, temperature, reaction time, catalyst loading,
and concentration provided us the optimal reaction conditions
as follows: 5 mol % TBADT and 10 mol % NiI2 with the
bipyridine L1 as ligand and K3PO4 as base in MeCN (0.2 M)
at room temperature under the irradiation (390 nm) for 4 h. In
this case, the reaction afforded the desired product 3a in 94%
Received: March 27, 2020
To realize the nickel/TBADT-cocatalyzed acylation reac-
tion, we utilized 4-bromo acetophenone (1a) and butanal (2a)
https://dx.doi.org/10.1021/acs.orglett.0c01121
© XXXX American Chemical Society
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A

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a
Table 1. Variation from the Optimal Reaction Conditions
Table 2. Evaluation of the Substrate Scope of Aryl Halides
a b
,
and Aliphatic Aldehydes
b
Entry
Variation from the Optimal Conditions
none
w/o TBADT
Yield (%)
1
2
94
0
3
w/o NiI2
0
4
w/o light
0
5
6
7
8
9
10
11
NiBr2 instead of NiI2
NiBr2·dme instead of NiI2
L2 instead of L1
82
80
trace
trace
81
<10
68
L3 instead of L1
2 mol % TBADT instead of 5 mol % TBADT
DABCO instead of K3PO4
acetone instead of MeCN
a
Unless otherwise specified, reactions were performed on a 0.2 mmol
scale of 4-bromo acetophenone (1a) with 3 equiv of butanal (2a)
using 5 mol % TBADT, 10 mol % NiI2, 10 mol % L1, and 1.1 equiv of
K3PO4 irradiated by a 34 W LED lamp (390 nm) in 1 mL of MeCN
b
at room temperature for 4 h. Yield of the isolated product after
column chromatography.
yield (entry 1). Conducting the reactions without either
TBADT or NiI2 gave rise to the complete shutdown of the
cross-coupling reaction (entries 2 and 3). Moreover, the
formation of the desired product 3a was not observed when
the reaction was carried out in the dark (entry 4). The use of
other Ni-salts resulted in lower yields (entries 5 and 6). In the
case of terpyridine (L2) or 1,10-phenanthroline (L3) as ligand,
only a trace amount of product was produced (entries 7 and
8). Lowering the catalyst loading of TBADT to 2 mol % led to
a decreased yield (entry 9). When K3PO4 was replaced by the
organic base DABCO, the yield diminished dramatically (entry
10). Furthermore, the reaction using acetone as solvent also
provided the product, albeit with lower efficiency (entry 11).
After establishing the optimal reaction conditions, we started
to evaluate the substrate spectrum of this Ni/TBADT-
cocatalyzed reaction by varying the structure of both aryl
halides and aldehydes (Table 2). All the reactions employing
bromobenzene with electron-withdrawing substitution pro-
ceeded smoothly under the standard reaction conditions,
furnishing the products 3a−k in moderate to excellent yields.
Furthermore, the use of alkyl- or vinyl-substituted bromoben-
zenes as precursors also posed no problem, and the
corresponding products 3l−o were obtained in moderate to
good yields. In contrast, the reactions using methoxy-
substituted phenyl bromides failed to deliver the products in
acceptable efficiency. In this case, the corresponding iodides
were utilized, instead, giving the products 3p and 3q in
moderate yields. Moreover, naphthyl and heteroaryl bromides
also turned out to be pertinent substrates for this Ni/TBADT-
cocatalyzed reaction, providing the products 3r−u in good to
high efficiency. Subsequently, a variety of aliphatic aldehydes
were surveyed, and the products 3v−z were afforded in
moderate to good yields. Generally, the undesired dehaloge-
a
Unless otherwise specified, reactions were performed on a 0.2 mmol
scale of the aryl bromides 1 with 3 equiv of aldehydes 2a using 5 mol
% TBADT, 10 mol % NiI2, 10 mol % L1, and 1.1 equiv of K3PO4
irradiated by a 34 W LED lamp (390 nm) in 1 mL of MeCN at room
b
c
temperature for 4 h. Yields of the isolated products. Reaction was
performed on 1 mmol scale. Reaction was performed with the
corresponding iodides.
d
nation of aryl halides accounts for all the above-mentioned
low-yielding reactions. In addition, aromatic aldehydes also
undergo the arylation under the standard conditions. However,
control studies found that these reactions proceed in the
absence of Ni-catalyst, and therefore these substrates were not
the focus of this manuscript.
B
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Next, we continued to investigate the substrate scope of this
Ni/TBADT cocatalyzed reaction by using aliphatic bromides
as the coupling partner with aldehydes. Unfortunately, in the
case of unactivated alkyl halides the desired acylation reaction
failed to deliver the cross-coupling product at a synthetically
useful level. Gratifyingly, ethyl 2-bromo acetate and its
fluorinated analogues turned out to be competitive coupling
partners with both substituted benzaldehydes and an aliphatic
aldehyde under modified reaction conditions (10 mol %
TBADT, NiBr2L1 complex as catalyst instead of the precatalyst
NiI2 and L1), providing an array of β-keto esters 5a−h in
moderate yields (Table 3). Moreover, we performed a control
AUTHOR INFORMATION
Corresponding Author
■
Chuan Wang − Hefei National Laboratory for Physical Science
at the Microscale and Department of Chemistry, University of
Science and Technology of China, Hefei, Anhui 230026, P. R.
China; Center for Excellence in Molecular Synthesis of CAS,
Hefei, Anhui 230026, P. R. China; orcid.org/0000-0002-
9219-1785; Email: chuanw@ustc.edu.cn
Authors
Pei Fan − Hefei National Laboratory for Physical Science at the
Microscale and Department of Chemistry, University of Science
and Technology of China, Hefei, Anhui 230026, P. R. China
Chang Zhang − Hefei National Laboratory for Physical Science
at the Microscale and Department of Chemistry, University of
Science and Technology of China, Hefei, Anhui 230026, P. R.
China
Table 3. Evaluation of the Substrate Scope of α-Bromo
a b
,
Acetates
Linchuan Zhang − Hefei National Laboratory for Physical
Science at the Microscale and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui
230026, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01121
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work is supported by National Natural Science
Foundation of China (Grant No. 21772183), Fundamental
Research Funds for the Central Universities (WK2060-
190086), and “1000-Youth Talents Plan” start-up funding as
well as University of Science and Technology of China.
a
REFERENCES
Unless otherwise specified, reactions were performed on a 0.2 mmol
scale of the aldehydes 2 with 3 equiv of the α-bromo acetates 4 using
10 mol % TBADT, 10 mol % NiBr2·L1, and 1.1 equiv of K3PO4
irradiated by a 34 W LED lamp (390 nm) in 1 mL of MeCN at room
■
(1) For reviews on benzoin reaction, see: (a) Giovannini, P. P.;
Bortolini, O.; Massi, A. Eur. J. Org. Chem. 2016, 2016, 4441−4459.
(b) Menon, R. S.; Biju, A. T.; Nair, V. Beilstein J. Org. Chem. 2016, 12,
444−461. (c) Gaggero, N.; Pandini, S. Org. Biomol. Chem. 2017, 15,
6867−6887.
b
c
temperature for 4 h. Yields of the isolated products. Reaction was
performed without TBADT.
(2) For reviews on Stetter reaction, see: (a) Christmann, M. Angew.
Chem., Int. Ed. 2005, 44, 2632−2634. (b) de Alaniz, J. R.; Rovis, A. T.
Synlett 2009, 2009, 1189−1207. (c) Yetra, S. R.; Patra, A.; Biju, A. T.
Synthesis 2015, 47, 1357−1378.
experiment for the reaction using aromatic aldehyde, in which
no TBADT was employed. In this case, no acylation reaction
occurred, confirming the indispensable role of TBADT in the
cocatalysis.
In summary, we developed a nickel/photo cocatalyzed
acylation of aryl halides and α-bromo acetates with both
aromatic and aliphatic aldehydes under mild reaction
conditions, providing a convenient and efficient access to a
variety of ketones. Notably, a series of sensitive functional
moieties are well tolerated in this reaction.
(3) For reviews on transition-metal-catalyzed hydroacylation of
alkenes and alkynes, see: (a) Jun, C.-H.; Jo, E.-A.; Park, J.-W. Eur. J.
Org. Chem. 2007, 2007, 1869−1881. (b) Willis, M. C. Chem. Rev.
2010, 110, 725−748. (c) Leung, J. C.; Krische, M. J. Chem. Sci. 2012,
3, 2202−2209. (d) Murphy, S. K.; Dong, V. M. Chem. Commun. 2014,
50, 13645−13649. (e) Ghosh, A.; Johnson, K. F.; Vickerman, K. L.;
Walker, J. A., Jr.; Stanley, L. M. Org. Chem. Front. 2016, 3, 639−644.
(f) Guo, R.; Zhang, G. Synlett 2018, 29, 1801−1806.
(4) (a) Huang, Y.-C.; Majumdar, K. K.; Cheng, C.-H. J. Org. Chem.
2002, 67, 1682−1684. (b) Ko, S.; Kang, B.; Chang, S. Angew. Chem.,
Int. Ed. 2005, 44, 455−457. (c) Ruan, J.; Saidi, O.; Iggo, J. A.; Xiao, J.
́
J. Am. Chem. Soc. 2008, 130, 10510−10511. (d) Alvarez-Bercedo, P.;
ASSOCIATED CONTENT
Flores-Gaspar, A.; Correa, A.; Martin, R. J. Am. Chem. Soc. 2010, 132,
■
́
466−467. (e) Flores-Gaspar, A.; Gutierrez-Bonet, A.; Martin, R. Org.
sı
* Supporting Information
Lett. 2012, 14, 5234−5237. (f) Suchand, B.; Satyanarayana, G. J. Org.
Chem. 2016, 81, 6409−6423. (g) Asachenko, A. F.; Valaeva, V. N.;
Kudakina, V. A.; Uborsky, D. A.; Izmer, V. V.; Kononovich, D. S.;
Voskoboynikov, A. Z. Russ. Chem. Bull. 2016, 65, 456−463.
(h) Vandavasi, J. K.; Hua, X.; Halima, H. B.; Newman, S. G.
Angew. Chem., Int. Ed. 2017, 56, 15441−15445. (i) Wakaki, T.; Togo,
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01121.
Description of experimental procedures, NMR spectra,
and ESI-MS data (PDF)
C
https://dx.doi.org/10.1021/acs.orglett.0c01121
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
T.; Yoshidome, D.; Kuninobu, Y.; Kanai, M. ACS Catal. 2018, 8,
3123−3128.
(5) (a) Pucheault, M.; Darses, S.; Genet, J. P. J. Am. Chem. Soc.
2004, 126, 15356−15357. (b) Qin, C.; Chen, J.; Wu, H.; Cheng, J.;
Zhang, Q.; Zuo, B.; Su, W.; Ding, J. Tetrahedron Lett. 2008, 49,
1884−1888. (c) Liao, Y.-X.; Hu, Q.-S. J. Org. Chem. 2010, 75, 6986−
6989. (d) Li, H.; Xu, Y.; Shi, E.; Wei, W.; Suo, X.; Wan, X. Chem.
Commun. 2011, 47, 7880−7882. (e) Karthikeyan, J.; Parthasarathy,
K.; Cheng, C.-H. Chem. Commun. 2011, 47, 10461−10463.
(f) Fukuyama, T.; Okamoto, H.; Ryu, I. Chem. Lett. 2011, 40,
1453−1455. (g) Gu, L.-J.; Jin, C.; Zhang, H.-T. Chem. - Eur. J. 2015,
21, 8741−8744. (h) Jin, C.; Gu, L.; Yuan, M. Catal. Sci. Technol.
2015, 5, 4341−4345. (i) Lei, C.; Zhu, D.; Tiu, V. I.; Zhou, J. S. Org.
Lett. 2019, 21, 5817−5822.
(6) Zhang, X.; MacMillan, D. W. C. J. Am. Chem. Soc. 2017, 139,
11353−11356.
̈
(7) Schirmer, T. E.; Wimmer, A.; Weinzierl, F. W. C.; Konig, B.
Chem. Commun. 2019, 55, 10796−10799.
(8) For reviews on TBADT-catalyzed reactions, see: (a) Hill, C. L.
Synlett 1995, 1995, 127−132. (b) Tzirakis, M. D.; Lykakis, I. N.;
Orfanopoulos, M. Chem. Soc. Rev. 2009, 38, 2609−2621. (c) Ravelli,
D.; Protti, S.; Fagnoni, M. Acc. Chem. Res. 2016, 49, 2232−2242.
(d) Ravelli, D.; Fagnoni, M.; Fukuyama, T.; Nishikawa, T.; Ryu, I.
ACS Catal. 2018, 8, 701−713.
(9) For recent examples on TBADT-catalyzed reactions, see:
(a) Dondi, D.; Fagnoni, M.; Molinari, A.; Maldotti, A.; Albini, A.
Chem. - Eur. J. 2004, 10, 142−148. (b) Dondi, D.; Fagnoni, M.;
Albini, A. Chem. - Eur. J. 2006, 12, 4153−4163. (c) Esposti, S.; Dondi,
D.; Fagnoni, M.; Albini, A. Angew. Chem., Int. Ed. 2007, 46, 2531−
2534. (d) Tzirakis, M. D.; Orfanopoulos, M. Org. Lett. 2008, 10, 873−
876. (e) Tzirakis, M. D.; Orfanopoulos, M. J. Am. Chem. Soc. 2009,
131, 4063−4069. (f) Protti, S.; Ravelli, D.; Fagnoni, M.; Albini, A.
Chem. Commun. 2009, 45, 7351−7353. (g) Ravelli, D.; Zema, M.;
Mella, M.; Fagnoni, M.; Albini, A. Org. Biomol. Chem. 2010, 8, 4158−
4164. (h) Ryu, I.; Tani, A.; Fukuyama, T.; Ravelli, D.; Fagnoni, M.;
Albini, A. Angew. Chem., Int. Ed. 2011, 50, 1869−1872. (i) Ravelli, D.;
Albini, A.; Fagnoni, M. Chem. - Eur. J. 2011, 17, 572−579.
(j) Halperin, S. D.; Fan, H.; Chang, S.; Martin, R. E.; Britton, R.
Angew. Chem., Int. Ed. 2014, 53, 4690−4693. (k) Okada, M.;
Fukuyama, T.; Yamada, K.; Ryu, I.; Ravelli, D.; Fagnoni, M. Chem. Sci.
2014, 5, 2893−2898. (l) Ravelli, D.; Zoccolillo, M.; Mella, M.;
Fagnoni, M. Adv. Synth. Catal. 2014, 356, 2781−2786. (m) Halperin,
S. D.; Kwon, D.; Holmes, M.; Regalado, E. L.; Campeau, L.-C.;
DiRocco, D. A.; Britton, R. Org. Lett. 2015, 17, 5200−5203.
(n) Okada, M.; Yamada, K.; Fukuyama, T.; Ravelli, D.; Fagnoni,
M.; Ryu, I. J. Org. Chem. 2015, 80, 9365−9369. (o) De Waele, V.;
Poizat, O.; Fagnoni, M.; Bagno, A.; Ravelli, D. ACS Catal. 2016, 6,
7174−7182. (p) Supranovich, V. I.; Levin, V. V.; Dilman, A. D. Org.
Lett. 2019, 21, 4271−4274. (q) Fan, P.; Zhang, C.; Lan, Y.; Lin, Z.;
Zhang, L.; Wang, C. Chem. Commun. 2019, 55, 12691−12694.
(r) Dong, J.; Wang, X.; Wang, Z.; Song, H.; Liu, Y.; Wang, Q. Chem.
Sci. 2020, 11, 1026−1031.
(10) (a) Filowitz, M.; Ho, R. K. C.; Klemperer, W. G.; Shum, W.
Inorg. Chem. 1979, 18, 93−103. (b) Yamase, T.; Usami, T. J. Chem.
Soc., Dalton Trans. 1988, 183−190.
(11) For examples of Ni/TBADT-cocatalyzed reaction, see:
(a) Perry, I. B.; Brewer, T. F.; Sarver, P. J.; Schultz, D. M.;
DiRocco, D. A.; MacMillan, D. W. C. Nature 2018, 560, 70−75.
(b) Fan, P.; Lan, Y.; Zhang, C.; Wang, C. J. Am. Chem. Soc. 2020, 142,
2180−2186.
D
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