Pd(II)-Catalyzed Direct ortho-C-H Acylation of Aromatic Ketones by Oxidative Decarboxylation of α-Oxocarboxylic Acids

Article abstract of DOI:10.1021/acs.orglett.7b00677

A Pd-catalyzed decarboxylative acylation of aromatic ketones with α-oxocarboxylic acids was developed, and 1,2-diacylbenzenes were formed in up to 90% yield with excellent ortho-selectivity. This work demonstrates the first successful attempt to direct C-H acylation of aromatic ketones without the need for prederivatization to imines. The acylation reaction was inhibited by radical scavengers such as TEMPO, and 2,2,6,6-tetramethylpiperidin-1-yl benzoate, the adduct of TEMPO and a benzoyl radical, has been isolated and characterized. This finding is compatible with the intermediacy of acyl radicals. A mechanism involving the reaction of the palladacyclic complexes of aryl ketones with acyl radicals is proposed.

Full text of DOI:10.1021/acs.orglett.7b00677

Letter
pubs.acs.org/OrgLett
Pd(II)-Catalyzed Direct ortho-C−H Acylation of Aromatic Ketones by
Oxidative Decarboxylation of α‑Oxocarboxylic Acids
Pui-Yiu Lee, Peiwen Liang, and Wing-Yiu Yu*
State Key Laboratory of Chirosciences and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic
University, Hung Hom, Kowloon, Hong Kong
S
* Supporting Information
ABSTRACT: A Pd-catalyzed decarboxylative acylation of
aromatic ketones with α-oxocarboxylic acids was developed,
and 1,2-diacylbenzenes were formed in up to 90% yield with
excellent ortho-selectivity. This work demonstrates the first
successful attempt to direct C−H acylation of aromatic
ketones without the need for prederivatization to imines. The acylation reaction was inhibited by radical scavengers such as
TEMPO, and 2,2,6,6-tetramethylpiperidin-1-yl benzoate, the adduct of TEMPO and a benzoyl radical, has been isolated and
characterized. This finding is compatible with the intermediacy of acyl radicals. A mechanism involving the reaction of the
palladacyclic complexes of aryl ketones with acyl radicals is proposed.
1,2-Diacylbenzenes are versatile precursors for some medicinally
important heterocycles such as phthalazines, isobenzofurans, and
isoindoles (Scheme 1).1 Moreover, 1,2-diacylbenzenes are also
atom abstraction of the aldehyde by tert-butoxy radicals)4,5
furnished the ortho-acylated ketone oximes. The 1,2-diacylben-
zenes were readily obtained by simple oxime deprotection with
HCl (Scheme 2a). Recently, Kim and co-workers developed a
Scheme 1. Some Medicinally Important Heterocycles Derived
from 1,2-Diacylbenzenes
Scheme 2. Synthesis of 1,2-Diacylbenzenes by Pd-Catalyzed
Oxidative C−H Acylation of Aryl Ketoimines
one-step protocol for palladium-catalyzed acylation of N-Boc
hydrazones, and 1,2-diacylbenzenes can be obtained in good
yields without the oxime deprotection step (Scheme 2b).6,7
Despite these advances, the necessity of a strong N-directing
group for successful transformations remains the inherent
limitation. It is envisaged that direct C−H acylation of aryl
ketones8 without the need for prederivatization to imines,
followed by deprotection, would be highly valuable. Here, we
present the Pd-catalyzed direct ortho-C−H acylation of aryl
ketones by decarboxylative coupling with α-oxocarboxylic acids
to produce 1,2-diacylbenzenes directly without the prederivati-
zation−deprotection step. The reaction is probably initiated by
ketone-directed ortho-C−H palladation, followed by decarbox-
ylative coupling of the α-oxocarboxylic acids (Scheme 3).
To assess the feasibility for the ketone-directed arene acylation
reaction, we examined the reaction of adamantyl phenyl ketone
(1f) with the bimetallic palladacyclic complex 1f-Pd as catalyst.9
employed as fluorescent reagents for amino acids and peptide
analysis.2 Notably, Friedel−Crafts acylation of aryl ketones with
acid chlorides is ineffective for 1,2-diacylbenzene synthesis
because of the meta-directing properties of the keto substituent.
Indeed, many currently available methods for 1,2-diacylbenzene
synthesis are laborious with poor generality.3 For instance,
oxidation of 1,3-diarylisobenzofurans by lead(IV) tetraacetate is
known to afford 1,2-diacylbenzenes in good yields.3e However,
the rather high reactivity and toxicity of the lead(IV) tetraacetate
hamper any widespread usage of this method.
In 2010, we reported a Pd-catalyzed, direct ortho-C−H
acylation of aryl ketone O-methyl oximes by cross-dehydrogen-
ative coupling with aldehydes using tert-butyl hydroperoxide
(TBHP) as oxidant.4a The ortho-selectivity was accomplished by
the oxime-directed ortho-C−H arene palladation, affording
palladacyclic complexes. Subsequent coupling of the palladacy-
clic complexes with acyl radicals (generated in situ via hydrogen
Received: March 7, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00677
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
and 1f-Pd (10 mol %) in the presence of (NH4)2S2O8 (3 equiv),
TFA (0.2 mL), and DCE (1 mL) at 60 °C for 24 h, the diketone
product 3f was formed in 44% yield (Scheme 4b).
Scheme 3. Selected Examples for Ketone-Directed ortho-C−H
Functionalization
For further optimization, we surveyed several experimental
parameters. By treating 1a (0.2 mmol) with phenylglyoxylic acid
2a (0.6 mmol), Pd(TFA)2 (10 mol %), (NH4)2S2O8 (3 equiv),
and TFA (0.5 mL) in anhydrous DCE (1 mL) at 80 °C for 24 h,
the diketone 3a was obtained in 46% yield (Table 1, entry 1). A
lower yield (31%) resulted when the reaction was performed in
undegassed conditions (entry 2). When Pd(OAc)2 (5 mol %)
was the catalyst with K2S2O8 (3 equiv) as the oxidant, the yield of
3a was slightly improved to 56% (entry 3). It should be noted that
no 3a formation was observed in the absence of either the Pd catalyst
or the oxidant. Other oxidants such as Na2S2O8, CAN, oxone, O2,
and organic peroxides failed to give better results (see Supporting
Information).
With TFA (0.2−0.5 mL) as additives, 3a was furnished in
comparable yields (entries 3 and 4). It was noted that employing
AcOH (0.5 mL) as additives led to poor results (entry 5). Other
acids such as TsOH and TfOH were ineffective as well for the
acylation reaction (see Supporting Information).
Hoping to achieve better product yields, we surmised that the
diketone formation could be limited by the rate of Pd(II)-
mediated C−H activation. Thus, faster radical generation is
probably unproductive for diketone formation. With this
hypothesis in mind, we adopted a batchwise addition protocol
for the phenylglyoxylic acid. In this work, when 1a (0.2 mmol)
was treated with phenylglyoxylic acid 2a in a batchwise addition
manner (0.2 mmol, 3 × 33.3 mol %/h), diketone 3a was
produced in 41% yield (entry 6). Significant yield improvement
was achieved by employing 3.0 equiv of 1a, and 3a was furnished
in 72% yield (entry 7).
When subjecting 1f-Pd (10 mol %) to a mixture of 1f (0.2
mmol), 4-chlorobenzaldehyde (3 equiv), TBHP (2 equiv), and
TFA (1 equiv) in DCE (1 mL), no acylation products were
obtained after heating at 80 °C for 24 h with Pd black being
formed (Scheme 4a). The failure is likely due to the unfavorable
competition between the aromatic ketones and the benzalde-
hydes for the coordination sites of the palladium complex.
Scheme 4. Preliminary Study on Acylation of Adamantyl
Phenyl Ketone Mediated by Palladacyclic Complex 1f-Pd
The yield was further improved when 4.0 and 6.0 equiv of 1a
were used, and 3a was isolated in 84% and 86% yields,
respectively (entries 8−9). A slightly lower 3a formation
(74%) was encountered when 2a and K2S2O8 were added all in
a single batch (entry 10). These results are consistent with our
hypothesis.
The substrate scope of the Pd-catalyzed decarboxylative
acylation was depicted in Scheme 5. Treating benzophenone 1a
(4 equiv) and phenylglyoxylic acid 2a (0.2 mmol, 3 × 33.3 mol
%/h) in the presence of Pd(OAc)2 (5 mol %), K2S2O8 (3 × 1
Inspired by the Pd-catalyzed decarboxylative acylation
reactions with α-oxocarboxylic acids10 first reported by the
research groups of Goossen10t and Ge,10r we turned to examine
α-oxocarboxylic acids as potential acylation reagents for the
ketone-directed C−H acylation reaction. Gratifyingly, when 1f
(0.2 mmol) was treated with phenylglyoxylic acid 2a (3 equiv)
a
Table 1. Reaction Optimization
b
entry
1
[Pd] (mol %)
oxidant (equiv)
acid additives (mL)
1a (equiv)
2a (equiv)
yield (%)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
(NH4)2S2O8 (3.0)
(NH4)2S2O8 (3.0)
K2S2O8 (3.0)
TFA (0.5)
TFA (0.5)
TFA (0.5)
TFA (0.2)
AcOH (0.5)
TFA (0.2)
TFA (0.2)
TFA (0.2)
TFA (0.2)
TFA (0.2)
1.0
1.0
1.0
1.0
1.0
1.0
3.0
4.0
6.0
4.0
3.0
3.0
3.0
3.0
3.0
46
31
56
50
trace
41
72
84
86
74
c
2
3
4
K2S2O8 (3.0)
5
K2S2O8 (3.0)
d
d
6
K2S2O8 (3.0)
1.0
d
d
7
K2S2O8 (3.0)
1.0
d
d
8
K2S2O8 (3.0)
1.0
d
d
9
K2S2O8 (3.0)
1.0
10
K2S2O8 (3.0)
1.0
a
b
Reaction conditions: 1a, 2a, Pd catalyst, oxidant (3 equiv), acid additives, DCE (1 mL) at 80 °C for 24 h, under a N2 atmosphere. Isolated yield.
c
d
Performed in undegassed conditions. K2S2O8 (3 × 1.0 equiv/h) and 2a (3 × 0.33 equiv/h) were added in a batchwise fashion.
B
DOI: 10.1021/acs.orglett.7b00677
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
The catalytic C−H acylation is probably initiated by the
Pd(II)-mediated arene C−H bond cleavage directed by the
adjacent ketone group. This is supported by the fact that the
cyclopalladated complex of adamantyl phenyl ketone (1f-Pd)
was kinetically competent for catalyzing the acylation of 1f with
phenylglyoxylic acid 2a, and 3f was formed in 44% yield (Scheme
4b). The Pd-catalyzed C−H acylation reaction exhibits a primary
kinetic H/D isotope effect (kH/kD) = 3.7.9,11 The KIEs were
determined by monitoring the acylation reaction by NMR with
an equimolar quantity of 1a and 1a-d10 as substrates. The
significant KIE observed in this work implies that the Pd-
mediated C−H cleavage step is likely to be the turnover-limiting
step.
Scheme 5. Substrate Scope of the Catalytic Acylation of
Aromatic Ketones
a b
,
The substituent effects of the arene C−H palladation have
been studied by examining the acylation reactions of a series of
para-substituted adamantyl aryl methanones (Y = OMe, Me, H,
F, and Cl). As depicted in Figure S1, a linear relationship of the
relative reaction rates with the Hammett constants σp was
revealed. The ρ value was found to be −4.1.11b,c,12 Since the
arene C−H palladation is the rate-determining step, this finding
is consistent with an electrophilic palladation mechanism with
development of a partial positive charge on the arene.
It is likely that the α-oxocarboxylic acids would serve as a
precursor for acyl radicals, which then mediate the diketone
formation via coupling with the palladacyclic intermediates. The
involvement of the acyl radicals was scrutinized by employing
TEMPO as a radical trapping agent.13 When 2a (0.2 mmol) was
treated with TEMPO (3 equiv), in the presence of Pd(OAc)2 (5
mol %) and K2S2O8 (1.5 equiv), the acyl radical−TEMPO
adduct was isolated in 79% yield (Scheme 6). In addition, the
diketone formation was also suppressed by TEMPO in a dosage-
dependent manner (see Supporting Information).
a
Reaction conditions: 1 (0.8 mmol), 2 (0.2 mmol; 3 × 33.3 mol %/h),
Pd(OAc)2 (5 mol %), K2S2O8 (3 × 1 equiv/h), TFA (0.2 mL), DCE
b
(1 mL) at 80 °C for 24 h, under a N2 atmosphere. 2 (0.2 mmol) and
K2S2O8 (3.0 equiv) were added in a single batch. 1-Ada is 1-adamantyl.
equiv/h), and TFA (0.2 mL) in DCE (1 mL) at 80 °C for 24 h
afforded 3a in 84% yield. Benzophenones with methyl and
methoxy substituents were transformed to the corresponding
diketones in 71−73% yields (3b and 3c). Aromatic ketones
bearing alkyl groups such as methyl and tert-butyl would undergo
ortho-C−H acylation to give diketones 3d−3e in 30% and 76%
yields, respectively. The apparent low yield of 3d is attributed to
the relatively slow cyclopalladation versus other ketones. As
expected, facile transformation of adamantyl aryl ketones with 2a
afforded 3f−3j in good-to-excellent yields. Substrates bearing
fused ring structures such as xanthone, 5-dibenzosuberenone,
and dibenzosuberone were also converted to their diketones (3k,
3l, and 3o) in 58−78% yields under the Pd-catalyzed conditions.
The scope of the α-oxocarboxylic acids was studied with
benzophenone and dibenzosuberone as substrates. α-Oxocar-
boxylic acids with a halogen substituent were effective coupling
partners, and diketones 3q and 3r were formed in 55−70%
yields. Alkyl substituents on α-oxocarboxylic acids such as
dimethyl and methyl were tolerated as exemplified by the
effective product [3n (64%) and 3p (62%)] formation. 2-
(Naphthalen-2-yl)-2-oxoacetic acid containing a bulky substitu-
ent would react with benzophenone to give 3m in 37% yield.
Indeed, the reactions involving sterically more demanding
2,3,4,5,6-pentamethylphenylglyoxylic acid were unsuccessful,
and no diketone products were obtained. The coupling reactions
with some aliphatic and heteroaromatic keto-acids such as
pyruvic acid and 2-oxo-2-(thiophen-2-yl) acetic acid were found
to be ineffective as well.
Scheme 6. Trapping of the Acyl Radicals by TEMPO
A plausible mechanism for this Pd-catalyzed C−H acylation is
depicted in Scheme 7. In the presence of TFA, Pd(OAc)2 would
be transformed to Pd(TFA)2 in situ. The acylation is probably
initiated by a ketone-directed ortho-selective electrophilic
palladation on the arene by the Pd(TFA)2. The palladacycle
would then undergo oxidative coupling with the acyl radicals,
Scheme 7. Proposed Reaction Mechanism
For unsymmetric benzophenones, the regioselectivity of the
acylation was examined by performing a competition experiment
with (4-bromophenyl)(p-tolyl)methanone as a substrate.
Apparently, the tolyl group would react preferentially versus
the bromophenyl group; a product ratio of 3.2:1 with a combined
yield of 80% (3s) was observed. We are gratified that at 1 mmol-
scale transformation of 1a by the Pd-catalyzed protocol afforded
3a in 62% yield (see Supporting Information).
C
DOI: 10.1021/acs.orglett.7b00677
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(5) Selected recent examples on radical-mediated transition metal-
catalyzed cross-coupling reactions, see: (a) Tellis, J. C.; Primer, D. N.;
Molander, G. A. Science 2014, 345, 433. (b) Karakaya, I.; Primer, D. N.;
Molander, G. A. Org. Lett. 2015, 17, 3294. (c) Ye, Y.; Sanford, M. S. J.
Am. Chem. Soc. 2012, 134, 9034.
which were in situ generated by decarboxylation of α-
oxocarboxylic acids.13 Reductive elimination from the putative
Pd(III) or Pd(IV) intermediate12b,14 would furnish 1,2-
diacylbenzenes together with the regeneration of the active
Pd(II) catalyst.
In conclusion, we have developed a Pd-catalyzed ortho-C−H
acylation of aromatic ketones via decarboxylative coupling with
α-oxocarboxylic acids. This reaction enables direct synthesis of
1,2-diacylbenzenes from aromatic ketones with high regiose-
lectivity and functional group tolerance. We anticipate that our
protocol may be applicable for other C−H coupling reactions.
(6) Sharma, S.; Kim, A.; Park, J.; Kim, M.; Kwak, J. H.; Jung, Y. H.; Park,
J. S.; Kim, I. S. Org. Biomol. Chem. 2013, 11, 7869.
(7) (a) Zhou, P.-X.; Ye, Y.-Y.; Liu, C.; Zhao, L.-B.; Hou, J.-Y.; Chen, D.-
Q.; Tang, Q.; Wang, A.-Q.; Zhang, J.-Y.; Huang, Q.-X.; Xu, P.-F.; Liang,
Y.-M. ACS Catal. 2015, 5, 4927. (b) Dong, Z.; Wang, J.; Ren, Z.; Dong,
G. Angew. Chem., Int. Ed. 2015, 54, 12664. (c) Huang, Y.; Zhu, R.; Zhao,
K.; Gu, Z. Angew. Chem., Int. Ed. 2015, 54, 12669.
(8) For a review on ketone-directed ortho-C−H functionalizations, see:
(a) Huang, Z.; Lim, H. N.; Mo, F.; Young, M. C.; Dong, G. Chem. Soc.
Rev. 2015, 44, 7764. For selected examples, see: (b) Sun, X.; Shan, G.;
ASSOCIATED CONTENT
* Supporting Information
■
S
Sun, Y.; Rao, Y. Angew. Chem., Int. Ed. 2013, 52, 4440. (c) Schroder, N.;
̈
Wencel-Delord, J.; Glorius, F. J. Am. Chem. Soc. 2012, 134, 8298.
(d) Shan, G.; Yang, X.; Ma, L.; Rao, Y. Angew. Chem., Int. Ed. 2012, 51,
13070. (e) Mo, F.; Trzepkowski, L. J.; Dong, G. Angew. Chem., Int. Ed.
2012, 51, 13075. (f) Xiao, B.; Gong, T.-J.; Xu, J.; Liu, Z.-J.; Liu, L. J. Am.
Chem. Soc. 2011, 133, 1466. (g) Gandeepan, P.; Parthasarathy, K.;
Cheng, C.-H. J. Am. Chem. Soc. 2010, 132, 8569. (h) Satoh, T.;
Kametani, Y.; Terao, Y.; Miura, M.; Nomura, M. Tetrahedron Lett. 1999,
40, 5345. (i) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.; Murai, S. Chem.
Lett. 1995, 24, 681. (j) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.;
Kamatani, A.; Sonoda, M.; Chatani, N. Nature 1993, 366, 529.
(9) Shan, G.; Yang, X.; Ma, L.; Rao, Y. Angew. Chem., Int. Ed. 2012, 51,
13070.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b00677.
General experimental procedures, physical character-
ization data, additional data, and NMR spectra of products
(PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: wing-yiu.yu@polyu.edu.hk.
ORCID
(10) (a) Wu, Y.; Sun, L.; Chen, Y.; Zhou, Q.; Huang, J.-W.; Miao, H.;
Luo, H.-B. J. Org. Chem. 2016, 81, 1244. (b) Zhou, C.; Li, P.; Zhu, X.;
Wang, L. Org. Lett. 2015, 17, 6198. (c) Gong, W.-J.; Liu, D.-X.; Li, F.-L.;
Gao, J.; Li, H.-X.; Lang, J.-P. Tetrahedron 2015, 71, 1269. (d) Ge, H.;
Miao, J. Synlett 2014, 25, 911. (e) Xu, B.; Liu, W.; Kuang, C. Eur. J. Org.
Chem. 2014, 2014, 2576. (f) Kim, M.; Mishra, N. K.; Park, J.; Han, S.;
Shin, Y.; Sharma, S.; Lee, Y.; Lee, E. K.; Kwak, J. H.; Kim, I. S. Chem.
Commun. 2014, 50, 14249. (g) Miao, J.; Ge, H. Org. Lett. 2013, 15, 2930.
(h) Sharma, S.; Kim, A.; Park, E.; Park, J.; Kim, M.; Kwak, J. H.; Lee, S.
H.; Jung, Y. H.; Kim, I. S. Adv. Synth. Catal. 2013, 355, 667. (i) Park, J.;
Kim, M.; Sharma, S.; Park, E.; Kim, A.; Lee, S. H.; Kwak, J. H.; Jung, Y.
H.; Kim, I. S. Chem. Commun. 2013, 49, 1654. (j) Yang, Z.; Chen, X.; Liu,
J.; Gui, Q.; Xie, K.; Li, M.; Tan, Z. Chem. Commun. 2013, 49, 1560.
(k) Li, H.; Li, P.; Tan, H.; Wang, L. Chem. - Eur. J. 2013, 19, 14432.
(l) Pan, C.; Jin, H.; Liu, X.; Cheng, Y.; Zhu, C. Chem. Commun. 2013, 49,
2933. (m) Li, Z. Y.; Li, D. D.; Wang, G. W. J. Org. Chem. 2013, 78, 10414.
(n) Wang, H.; Guo, L.-N.; Duan, X.-H. Org. Lett. 2012, 14, 4358. (o) Li,
M.; Wang, C.; Ge, H. Org. Lett. 2011, 13, 2062. (p) Li, M.; Wang, C.;
Fang, P.; Ge, H. Chem. Commun. 2011, 47, 6587. (q) Li, M.; Ge, H. Org.
Lett. 2010, 12, 3464. (r) Fang, P.; Li, M.; Ge, H. J. Am. Chem. Soc. 2010,
132, 11898. (s) Shang, R.; Fu, Y.; Li, J.-B.; Zhang, S.-L.; Guo, Q.-X.; Liu,
L. J. Am. Chem. Soc. 2009, 131, 5738. (t) Goossen, L. J.; Rudolphi, F.;
Oppel, C.; Rodriguez, N. Angew. Chem., Int. Ed. 2008, 47, 3043.
(11) Intermolecular primary KIE (kH/kD) values of 2−6 have been
reported for related studies. Selected examples, for chlorination (kH/kD
= 2.6): (a) Sun, X.; Shan, G.; Sun, Y.; Rao, Y. Angew. Chem., Int. Ed.
2013, 52, 4440. For acetoxylation (kH/kD = 4.3): (b) Stowers, K. J.;
Sanford, M. S. Org. Lett. 2009, 11, 4584. (kH/kD = 1.9): (c) Desai, L. V.;
Stowers, K. J.; Sanford, M. S. J. Am. Chem. Soc. 2008, 130, 13285.
(12) Related studies on palladacycles with partial positive charge
developed: (a) Whitfield, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2007,
129, 15142. (b) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am.
Chem. Soc. 2005, 127, 13754. For related Hammett correlation studies
for Pd-catalyzed ortho-C−H activation of arenes. See 11c (acetoxylation,
ρ = −2.01).
Wing-Yiu Yu: 0000-0003-3181-8908
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank The Hong Kong Research Grants Council (PolyU
153037/14P) for financial support.
REFERENCES
■
(1) (a) Chanda, T.; Chowdhury, S.; Anand, N.; Koley, S.; Gupta, A.;
Singh, M. S. Tetrahedron Lett. 2015, 56, 981. (b) Sivasakthikumaran, R.;
Nandakumar, M.; Mohanakrishnan, A. K. J. Org. Chem. 2012, 77, 9053.
(c) Bunce, R. A.; Harrison, T.; Nammalwar, B. Heterocycl. Commun.
2012, 18, 123. (d) Jacq, J.; Einhorn, C.; Einhorn, J. Org. Lett. 2008, 10,
3757. (e) Kotali, A.; Harris, P. A. Org. Prep. Proced. Int. 2003, 35, 583.
(f) Kotali, A. Org. Mass Spectrom. 1991, 26, 889. (g) Nan’ya, S.; Fujii, T.;
Butsugan, Y. J. Heterocycl. Chem. 1990, 27, 1407.
(2) (a) Beale, S. C.; Savage, J. C.; Wiesler, D.; Wietstock, S. M.;
Novotny, M. Anal. Chem. 1988, 60, 1765. (b) Ebrahim, H.;
Dakshinamurti, K. Anal. Biochem. 1986, 154, 282. (c) Sternson, L. A.;
Stobaugh, J. F.; Repta, A. J. Anal. Biochem. 1985, 144, 233. (d) Roth, M.
Anal. Chem. 1971, 43, 880.
(3) (a) Lo Fiego, M. J.; Badajoz, M. A.; Silbestri, G. F.; Lockhart, M. T.;
Chopa, A. B. J. Org. Chem. 2008, 73, 9184. (b) Kumar, S.; Kumar, D.
Synth. Commun. 2008, 38, 3683. (c) Xian, H.; Qing, Z.; Jizheng, Z. Synth.
Commun. 2001, 31, 2413. (d) Moriarty, R. M.; Berglund, B. A.; Rao, M.
S. C. Synthesis 1993, 1993, 318. (e) Kotali, A.; Tsoungas, P. G.
Tetrahedron Lett. 1987, 28, 4321. (f) Metlesics, W.; Anton, T.;
Chaykovsky, M.; Toome, V. J. Org. Chem. 1968, 33, 2874.
(4) Examples of radical-mediated Pd-catalyzed C−H cross coupling
reactions, for acylation: (a) Chan, C.-W.; Zhou, Z.; Chan, A. S. C.; Yu,
W.-Y. Org. Lett. 2010, 12, 3926. (b) Chan, C.-W.; Zhou, Z.; Yu, W.-Y.
Adv. Synth. Catal. 2011, 353, 2999. (c) Yu, W.-Y.; Sit, W. N.; Lai, K.-M.;
Zhou, Z.; Chan, A. S. C. J. Am. Chem. Soc. 2008, 130, 3304. For
arylation: (d) Yu, W.-Y.; Sit, W. N.; Zhou, Z.; Chan, A. S. C. Org. Lett.
2009, 11, 3174. For malonylation: (e) Chan, W.-W.; Zhou, Z.; Yu, W.-
Y. Chem. Commun. 2013, 49, 8214. For carboxylation: (f) Sit, W.-N.;
Chan, C.-W.; Yu, W.-Y. Molecules 2013, 18, 4403.
(13) Xu, N.; Liu, J.; Li, D.; Wang, L. Org. Biomol. Chem. 2016, 14, 4749.
(14) (a) Powers, D. C.; Geibel, M. A. L.; Klein, J. E. M. N.; Ritter, T. J.
Am. Chem. Soc. 2009, 131, 17050. (b) Powers, D. C.; Ritter, T. Nat.
Chem. 2009, 1, 302. (c) Dick, A. R.; Kampf, J. W.; Sanford, M. S. J. Am.
Chem. Soc. 2005, 127, 12790.
D
DOI: 10.1021/acs.orglett.7b00677
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