Synthesis of bis(heteroaryl) ketones by removal of benzylic CHR and CO groups

Article abstract of DOI:10.1002/anie.201308785

A copper-catalyzed method for synthesis of diaryl ketones (Ar-CO-Ar′) through removal of benzylic -CH₂-, -CO-, and -CHR- groups from Ar-CO-CXR-Ar′ has been discovered. A number of symmetrical and unsymmetrical heterocyclic ketones, which are usually difficult to synthesize, can be prepared in good to excellent yields. This method was applied to the synthesis of the nonsteroidal anti-inflammatory drug suprofen (47 % yield over three steps). Based on preliminary mechanistic and kinetic studies, an active Cu/O₂ species is proposed to mediate the rearrangement reaction. Snip snip: A copper-catalyzed method for synthesis of diaryl ketones by removal of benzylic CH₂, CO, and CHR groups has been discovered. A number of symmetrical and unsymmetrical heterocyclic ketones, which are usually difficult to synthesize, can be prepared in good to excellent yields. Preliminary mechanistic studies indicate that an active Cu/O₂ species mediates the rearrangement. Copyright

Full text of DOI:10.1002/anie.201308785

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DOI: 10.1002/anie.201308785
Heterocycles
Synthesis of Bis(heteroaryl) Ketones by Removal of Benzylic CHR and
CO Groups**
Arun Maji, Sujoy Rana, Akanksha, and Debabrata Maiti*
Abstract: A copper-catalyzed method for synthesis of diaryl
ketones (Ar-CO-Ar’) through removal of benzylic -CH2-,
-CO-, and -CHR- groups from Ar-CO-CXR-Ar’ has been
discovered. A number of symmetrical and unsymmetrical
heterocyclic ketones, which are usually difficult to synthesize,
can be prepared in good to excellent yields. This method was
applied to the synthesis of the nonsteroidal anti-inflammatory
drug suprofen (47% yield over three steps). Based on
preliminary mechanistic and kinetic studies, an active Cu/O2
species is proposed to mediate the rearrangement reaction.
Figure 2. Select examples of diaryl ketones as pharmacueticals.
C
arbon–carbon bonds constitute the basic foundation of
synthetic chemistry. Protocols for the generation and cleavage
of such bonds are indispensable for the synthesis of new
organic scaffolds. Although carbon–carbon bond-formation
techniques have been studied extensively, the cleavage of
carbon–carbon bonds is still a difficult objective. The inert
nature of the carbon–carbon bond makes its cleavage
problematic, and gaining control of it is even more challeng-
ing.[1] Despite reports on carbon–carbon single-,[2] double-,[3]
amide,[7] aldehyde,[8] acyl transfer,[9] ketonic partner
exchange,[10] and rearrangement reactions.[11] However,
diaryl ketone and heterocyclic ketone synthesis starting
from a-arylated ketones by C(CO)-C(a) bond cleavage is
yet to be reported.
Herein, we report an effective method of removing
a benzylic carbon moiety to synthesize symmetrical/unsym-
metrical diaryl ketones and bis(heteroaryl) ketones. This
method connects the benzylic aromatic ring directly to the
ketone by eliminating the benzylic -CH2-, -CHR-, and -CO-
groups without changing the connectivity with the ring
(Scheme 1).
and triple-bond cleavage,[4] the development of a C C bond-
disconnection approach to construct a new C C bond still
remains a formidable task.
Industrially ketones are utilized as pharmaceutical drugs,
polymer precursors, and as biologically and chemically
important building blocks. Development of a new synthetic
approach for their synthesis is therefore of great significance
(Figures 1 and 2). Synthetically C(CO)-C(a) bond cleavage
has been utilized (Figure 1) to generate acid,[5] ester,[6]
À
À
Scheme 1. Diaryl ketone synthesis by C(CO)-C(a) cleavage.
We envisioned removal of the a-carbon centers of 2-
phenylacetophenone through formation of an imine and
subsequent Cu/O2 chemistry/rearrangement reactions. Such
a reaction, in essence, also mimics DNA demethylase activity
wherein an active methyl group is removed from nucleotide in
DNA.[12] Notably, 2-phenylacetophenone derivatives are
accessible by various methods, for example, a-arylation of
acetophenone,[13] Wacker oxidation of internal olefin,[3b,14]
etc.[15]
Figure 1. The cleavage of the C(CO)-C(a) bond of a ketone.
[*] A. Maji, S. Rana, Akanksha, Prof. D. Maiti
Department of Chemistry, Indian Institute of Technology Bombay
Powai, Mumbai-400 076 (India)
We started our investigation by reacting an imine,
generated in situ from aniline and 2-phenylacetophenone,
with a Cu/O2 active species to induce rearrangement reaction
(Table 1). Polar aprotic solvents such as DMF and DMSO
proved to be high yielding. DMSO is likely to stabilize the
copper catalyst and also assist in the aerobic oxidation
process.[16] Subsequently we realized p-toluidine was better
E-mail: dmaiti@chem.iitb.ac.in
[**] This activity was supported by DST, India. Financial support
received from CSIR-India (A.M. and S.R.) is gratefully acknowl-
edged. D.M. thanks Prof. Steve Buchwald (MIT) for insightful
discussions.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201308785.
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Table 1: Optimization of reaction conditions.[17]
Table 3: Generation of diaryl ketone through removal of benzylic -CHR-
groups.
Entry
Cu salt
Solvent
Yield [%]
Substrate
Product
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OTf)2
CuCl2
CuCO3
CuBr
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
TFT[c]
85
65
65
n.d.
66
85[a]
85[b]
30[a,b]
4
2
2
9
10
11
anisole[c]
cyclohexane[c]
[a] Ethylbenzoate was isolated in 65% yield.
[a] 2h. [b] 20 mol% toluidine. [c] K2CO3. DMSO=dimethylsufoxide,
Tf =trifluoromethansulfonyl, TFT=trifluorotoluene.
obtained by removal of -CHBr- (3b), -CHPh- (3c), -CHiPr-
(3d), and -CH(OEt)- (3e) groups.
for this reaction compared to aniline, and use of base was
found to be beneficial. Under the optimized reaction
conditions, the demethylenated product benzophenone (2a’)
was obtained from 2-phenylacetophenone (2a) in 85% yield
(GC). The reaction was equally successful with both isolated
and in situ generated imines.[17] Without ArNH2, 2a’ was
formed in only 20% yield. In the absence of O2, the formation
of an imine was observed without a trace of the desired diaryl
ketone compound.[17]
At first 2-phenylacetophenone derivatives were tested
(Table 2) under the standard reaction conditions. A chloro
(2b) and a bromo (2c) phenylacetophenone gave the desired
demethylenated product in 70% (2b’) and 68% (2c’) yield,
respectively. Notably, unsymmetrical a hetero-carbocylic
ketone can also be synthesized by this method (2e’).
Next, we tested a variety of intervening groups other than
-CH2- (Table 3). Diaryl ketones can also be obtained from
benzoin derivatives (3a and 3 f). Benzophenone was also
Efforts were made to apply this methodology for the
synthesis of symmetrical and unsymmetrical heterocyclic
ketones (Table 4). The classical method of diaryl ketone
synthesis involving arylmetal species[18] and Friedel–Crafts
acylations are often incompatible for heteroaromatic
moiety.[19] Although carbonylative methods[20] are known for
heterocylic ketone synthesis, formation of homocoupled
products without insertion of CO restricts its applicabili-
ty.[20d,21] Alternative pathways of aldehyde arylation have
Table 4: Bis(heteroaryl) ketone synthesis.
Substrate
Product
Table 2: Removal of benzylic -CH2- groups.
Substrate
Product
All the reactions were performed in 0.25 mmol scale. [a] 2h, [b] 12 h,
[c] 6h.
All the reactions were done in 0.25 mmol scale. [a] 12 h. [b] 6 h. [c] 8 h.
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been developed for the synthesis of bis(heteroaryl)
ketones.[22] Still new methods for the synthesis of such ketones
are of great importance.
A dipyridyl ketone was obtained from two distinct
substrates, 4a and 4d. Unsymmetrical heterocylic ketones
such as 4b’, 4c’, 4e’, and 4 f’ were obtained in good to
excellent yields. Pyridin-3-yl(thiophen-2-yl)methanone (4c’),
the precursor of an insulin release stimulator,[23] was also
synthesized under the optimized reaction conditions in 88%
yield. Suprofen (profenal), a nonsteroidal anti-inflammatory
drug from Janssen Pharmaceutica, can be synthesized follow-
ing present method in 47% overall yield (3 steps;
Scheme 2).[24]
Scheme 4. Isotope-labeling experiment.
established under an initial-slope method (see Figure S2),[17]
which indicates the involvement of two molecules of 1.[26] The
reaction was complete within 2 hours (2a) using 1.2 equiv-
alents toluidine. Upon further progress the amine oxidizes to
the diazo compound, 1,2-di-p-tolyldiazene (see Figures S3
and S).[17]
Since PhCOCOPh was obtained from PhCH2COPh and
PhCH(OH)COPh in 61% and 98%, respectively, at room
temperature,[17] diketo compounds were subsequently
explored as the starting material for synthesizing diaryl
ketones.
Benzil (5a) produced benzophenone in 80% yield
(Table 5). In the presence of a methoxy group on both
phenyl rings of benzil, the desired product was obtained in
71% yield (5b’). Notably, in this case the 3-substituted
benzylic group was converted into the corresponding 3-
substituted aryl group without any internal scrambling (5b).
This outcome indicates that a concerted rearrangement
pathway is likely to be operative. In case of a cyclic system
like phenanthraquinone the desired fluorenone 5c’ was
obtained in 75% yield. The symmetrical diheterocyclic
ketones 5d’ and 5e’ were also generated from corresponding
diketo precursors 5d and 5e. In all these cases, a benzylic
-CO- moiety was removed successfully to produce the diaryl
Scheme 2. Synthesis of suprofen. THF=tetrahydrofuran, xant-
phos=9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene.
A series of experiments were carried out to gain insights
into the reaction mechanism. Under standard reaction con-
ditions, a mixture of two a-phenylacetophenone derivatives
gave the corresponding diaryl ketones only, without a trace of
crossover product (Scheme 3). Such an observation indicates
that a concerted rearrangement reaction is likely to be
operative. Further, 2-ethoxy-2-phenylacetophenone (3e) pro-
duced ethyl benzoate as the major product, thus indicating
close correlation between migratory apptitude of the a sub-
stituents and that of the product composition (see Scheme S3
in the Supporting Information).[17]
Table 5: Ketone synthesis by removal of benzylic -CO- groups.
Substrate
Product
Scheme 3. Crossover experiment.
In the presence of a radical scavenger, the desired product
yield was significantly reduced (see Scheme S1).[17,25] With
18O2, incorporation of 18O into the benzophenone product was
been observed (Scheme 4).
The progress of the reaction was monitored using
a number of different excess experiments with respect to 2-
phenylacetophenone.[17] A second-order rate dependance was
All the reactions were done in 0.25 mmol scale. [a] 2 h. [b] 8 h.
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16, 9712 – 9721; f) M. Murakami, T. Matsuda, Chem. Commun.
2011, 47, 1100 – 1105.
ketone product. Notably, the yield obtained from benzil (5a)
is comparable to that of 2a (Table 2).
[2] a) P. D. Pohlhaus, R. K. Bowman, J. S. Johnson, J. Am. Chem.
Soc. 2004, 126, 2294 – 2295; b) J. J. Lian, A. Odedra, C. J. Wu,
R. S. Liu, J. Am. Chem. Soc. 2005, 127, 4186 – 4187; c) A. Gunay,
W. D. Jones, J. Am. Chem. Soc. 2007, 129, 8729 – 8735; d) M.
Tobisu, R. Nakamura, Y. Kita, N. Chatani, J. Am. Chem. Soc.
2009, 131, 3174 – 3175; e) D. E. Herbert, J. B. Gilroy, A. Staubitz,
M. F. Haddow, J. N. Harvey, I. Manners, J. Am. Chem. Soc. 2010,
132, 1988 – 1998; f) X. Wu, L. Li, J. Zhang, Chem. Commun.
2011, 47, 7824 – 7826; g) F. Chen, C. Qin, Y. Cui, N. Jiao, Angew.
Chem. 2011, 123, 11689 – 11693; Angew. Chem. Int. Ed. 2011, 50,
11487 – 11491; h) H. Li, Y. Li, X.-S. Zhang, K. Chen, X. Wang,
Z. J. Shi, J. Am. Chem. Soc. 2011, 133, 15244 – 15247; i) K. Nakai,
T. Kurahashi, S. Matsubara, J. Am. Chem. Soc. 2011, 133, 11066 –
11068; j) C. Qin, T. Shen, C. Tang, N. Jiao, Angew. Chem. 2012,
124, 7077 – 7081; Angew. Chem. Int. Ed. 2012, 51, 6971 – 6975;
k) X. S. Zhang, Y. Li, H. Li, K. Chen, Z. Q. Lei, Z. J. Shi, Chem.
Eur. J. 2012, 18, 16214 – 16225; l) J. Terao, M. Tomita, S. P. Singh,
N. Kambe, Angew. Chem. 2009, 121, 150 – 154; Angew. Chem.
Int. Ed. 2009, 48, 144 – 147.
Based on preliminary mechanistic studies, we proposed
imine formation (2) and subsequent Cu/O2-mediated oxida-
tion of the benzylic position to the corresponding ketone (3;
Scheme 5).[17,27,28] The pathway for the generation of 3
depends on the nature of the starting materials. For example,
[3] a) T. Takemori, A. Inagaki, H. Suzuki, J. Am. Chem. Soc. 2001,
123, 1762 – 1763; b) B. R. Travis, R. S. Narayan, B. Borhan, J.
Am. Chem. Soc. 2002, 124, 3824 – 3825; c) V. Kogan, M. M.
Quintal, R. Neumann, Org. Lett. 2005, 7, 5039 – 5042; d) K.
Miyamoto, Y. Sei, K. Yamaguchi, M. Ochiai, J. Am. Chem. Soc.
2009, 131, 1382 – 1383; e) A. Sattler, G. Parkin, Nature 2009, 457-
462, 523 – 526; f) R. Lin, F. Chen, N. Jiao, Org. Lett. 2012, 14,
4158 – 4161.
[4] a) T. Shimada, Y. Yamamoto, J. Am. Chem. Soc. 2003, 125,
6646 – 6647; b) S. Datta, C. L. Chang, K. L. Yeh, R. S. Liu, J. Am.
Chem. Soc. 2003, 125, 9294 – 9295; c) Y. Liu, F. Song, S. Guo, J.
Am. Chem. Soc. 2006, 128, 11332 – 11333; d) A. Wang, H. Jiang,
J. Am. Chem. Soc. 2008, 130, 5030 – 5031; e) T. Shen, T. Wang, C.
Qin, N. Jiao, Angew. Chem. 2013, 125, 6809 – 6812; Angew.
Chem. Int. Ed. 2013, 52, 6677 – 6680; f) C. H. Jun, H. Lee, C. W.
Moon, H. S. Hong, J. Am. Chem. Soc. 2001, 123, 8600 – 8601;
g) L. J. Wang, H. T. Zhu, L. Lu, F. Yang, X. Y. Liu, Y. M. Liang,
Org. Lett. 2012, 14, 1990 – 1993.
Scheme 5. Plausible catalytic pathway.
the transformation of -CH2- to -CO- involves formation of an
a-hydroxy ketone intermediate, which upon oxidation gen-
erates the diketo derivative 3.[17] In the case of -CHBr- the
reaction proceeds through a Kornblum oxidation.[29] Once
formed, 3 undergoes a benzylic acid rearrangement leading to
7,[30] which decomposes to the desired ketone product.
In summary, we have developed a copper-catalyzed
method for the synthesis of diaryl ketones and bis(heteroaryl)
ketones by removal of benzylic -CH2-, -CO-, and -CHR-
groups under aerobic conditions. This transformation intro-
duces direct bonding between the carbonyl carbon atom and
the b-carbon atom by eliminating the a-carbon atom and
keeping the bond connectivity intact for rest of the molecule.
[5] a) W. von E. Doering, R. M. Haines, J. Am. Chem. Soc. 1954, 76,
482 – 486; b) V. Le Boisselier, C. Coin, M. Postel, E. Dunach,
Tetrahedron 1995, 51, 4991 – 4996.
[6] a) N. Zhang, J. Vozzolo, J. Org. Chem. 2002, 67, 1703 – 1704; b) S.
Paria, P. Halder, T. K. Paine, Angew. Chem. 2012, 124, 6299 –
6303; Angew. Chem. Int. Ed. 2012, 51, 6195 – 6199; c) C. Zhang,
P. Feng, N. Jiao, J. Am. Chem. Soc. 2013, 135, 15257 – 15262.
[7] a) J. Y. Becker, L. L. Miller, T. M. Siegel, J. Am. Chem. Soc.
1975, 97, 849 – 853; b) K. Ishihara, T. Yano, Org. Lett. 2004, 6,
1983 – 1986; c) Y. Kuninobu, T. Uesugi, A. Kawata, K. Takai,
Angew. Chem. 2011, 123, 10590 – 10592; Angew. Chem. Int. Ed.
2011, 50, 10406 – 10408.
[8] L. Zhang, X. Bi, X. Guan, X. Li, Q. Liu, B. D. Barry, P. Liao,
Angew. Chem. 2013, 125, 11513 – 11517; Angew. Chem. Int. Ed.
2013, 52, 11303 – 11307.
[9] M. Arisawa, M. Kuwajima, F. Toriyama, G. Z. Li, M. Yamaguchi,
Org. Lett. 2012, 14, 3804 – 3807.
Received: October 8, 2013
Revised: December 10, 2013
Published online: January 31, 2014
[10] J. A. Ahn, D. H. Chang, Y. J. Park, Y. R. Yon, A. Loupy, C. H.
Jun, Adv. Synth. Catal. 2006, 348, 55 – 58.
[11] a) H. Yoshida, T. Kishida, M. Watanabe, J. Ohshita, Chem.
Commun. 2008, 5963 – 5965; b) A. M. Dreis, C. J. Douglas, J.
Am. Chem. Soc. 2009, 131, 412 – 413.
Keywords: copper · heterocycles · ketones · oxygen ·
reaction mechanisms
.
[12] a) K. I. Ladwein, M. Jung, Angew. Chem. 2011, 123, 12347 –
12349; Angew. Chem. Int. Ed. 2011, 50, 12143 – 12145; b) M.
Mꢀnzel, D. Globisch, T. Carell, Angew. Chem. 2011, 123, 6588 –
6596; Angew. Chem. Int. Ed. 2011, 50, 6460 – 6468; c) T.
Pfaffeneder, B. Hackner, M. Truss, M. Mꢀnzel, M. Mꢀller,
[1] a) R. H. Crabtree, Chem. Rev. 1985, 85, 245 – 269; b) B. Rybtch-
inski, D. Milstein, Angew. Chem. 1999, 111, 918 – 932; Angew.
Chem. Int. Ed. 1999, 38, 870 – 883; c) C. H. Jun, Chem. Soc. Rev.
2004, 33, 610 – 618; d) M. Tobisu, N. Chatani, Chem. Soc. Rev.
2008, 37, 300 – 307; e) A. Masarwa, I. Marek, Chem. Eur. J. 2010,
Angew. Chem. Int. Ed. 2014, 53, 2428 –2432
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2431

.
Angewandte
Communications
C. A. Deiml, C. Hagemeier, T. Carell, Angew. Chem. 2011, 123,
7146 – 7150; Angew. Chem. Int. Ed. 2011, 50, 7008 – 7012.
[13] a) K. Chen, H. Li, Y. Li, X.-S. Zhang, Z. Q. Lei, Z. J. Shi, Chem.
Sci. 2012, 3, 1645 – 1649; b) N. Chernyak, S. L. Buchwald, J. Am.
Chem. Soc. 2012, 134, 12466 – 12469; c) K. D. Hesp, R. J.
Lundgren, M. Stradiotto, J. Am. Chem. Soc. 2011, 133, 5194 –
5197; d) M. Jørgensen, S. Lee, X. Liu, J. P. Wolkowski, J. F.
Hartwig, J. Am. Chem. Soc. 2002, 124, 12557 – 12565; e) M. R.
Biscoe, S. L. Buchwald, Org. Lett. 2009, 11, 1773 – 1775; f) X.
Dai, N. A. Strotman, G. C. Fu, J. Am. Chem. Soc. 2008, 130,
3302 – 3303; g) A. E. Allen, D. W. C. MacMillan, J. Am. Chem.
Soc. 2011, 133, 4260 – 4263; h) C. C. C. Johansson, T. J. Colacot,
Angew. Chem. 2010, 122, 686; Angew. Chem. Int. Ed. 2010, 49,
676.
1888; e) C. Zhou, R. C. Larock, J. Am. Chem. Soc. 2004, 126,
2302 – 2303; f) C. Duplais, F. Bures, I. Sapountzis, T. J. Korn, G.
Cahiez, P. Knochel, Angew. Chem. 2004, 116, 3028 – 3030;
Angew. Chem. Int. Ed. 2004, 43, 2968 – 2970.
[23] P. Jakobsen, P. Madsen, H. Andersen, Eur. J. Med. Chem. 2003,
38, 357 – 362.
[24] H. Neumann, A. Brennfuhrer, M. Beller, Adv. Synth. Catal.
2008, 350, 2437.
[25] a) A. Deb, S. Manna, A. Modak, T. Patra, S. Maity, D. Maiti,
Angew. Chem. 2013, 125, 9929 – 9932; Angew. Chem. Int. Ed.
2013, 52, 9747 – 9750; b) A. Deb, S. Manna, A. Maji, U. Dutta, D.
Maiti, Eur. J. Org. Chem. 2013, 5251 – 5256; c) S. Maity, S.
Manna, S. Rana, T. Naveen, A. Mallick, D. Maiti, J. Am. Chem.
Soc. 2013, 135, 3355 – 3358.
[14] a) D. Yang, C. Zhang, J. Org. Chem. 2001, 66, 4814 – 4818; b) D.
Xing, B. Guan, G. Cai, Z. Fang, L. Yang, Z. Shi, Org. Lett. 2006,
8, 693 – 696.
[15] a) Y. Su, X. Sun, G. Wu, N. Jiao, Angew. Chem. Int. Ed. 2013, 52,
9808 – 9812; b) Q. L. Xu, H. Gao, M. Yousufuddin, D. H. Ess, L.
Kurti, J. Am. Chem. Soc. 2013, 135, 14048 – 14051.
[16] a) S. S. Stahl, Science 2005, 309, 1824 – 1826; b) S. Monge, V.
Darcos, D. M. Haddleton, J. Polym. Sci. Part A 2004, 42, 6299 –
6308.
[17] See the Supporting Information for a detailed description.
[18] a) J. March, Advanced Organic Chemistry, 3rd ed., Wiley, New
York, 1985; b) R. C. Larock, Comprehensive Organic Trans-
formations, VCH, New York, 1989; c) T. Katoh, O. Ohmori, K.
Iwasaki, M. Inoue, Tetrahedron 2002, 58, 1289 – 1299.
[19] C. K. McGill, A. Rappa, R. K. Alan, Advanced Heterocyclic
Chemistry, Vol. 44, Academic Press, New York, 1988, pp. 1 – 79.
[20] a) R. F. Heck, J. Am. Chem. Soc. 1968, 90, 5546 – 5548; b) T.
Ishiyama, H. Kizaki, T. Hayashi, A. Suzuki, N. Miyaura, J. Org.
Chem. 1998, 63, 4726 – 4731; c) H. Li, M. Yang, Y. Qi, J. Xue, Eur.
J. Org. Chem. 2011, 2662 – 2667; d) S. Couve-Bonnaire, J. F. O.
Carpentier, A. Mortreux, Y. Castanet, Tetrahedron 2003, 59,
2793 – 2799; e) T. Zhou, Z. C. Chen, Synth. Commun. 2002, 32,
3431 – 3435.
[21] X. F. Wu, H. Neumann, M. Beller, Chem. Rev. 2012, 112, 1 – 35.
[22] a) Q. Y. Toh, A. McNally, S. Vera, N. Erdmann, M. J. Gaunt, J.
Am. Chem. Soc. 2013, 135, 3772 – 3775; b) M. Pucheault, S.
Darses, J. P. Genet, J. Am. Chem. Soc. 2004, 126, 15356 – 15357;
c) Y. C. Huang, K. K. Majumdar, C. H. Cheng, J. Org. Chem.
2002, 67, 1682 – 1684; d) C. Qin, J. Chen, H. Wu, J. Cheng, Q.
Zhang, B. Zuo, W. Su, J. Ding, Tetrahedron Lett. 2008, 49, 1884 –
[26] After 2 h, the yield of the ketone product remains unchanged.
However, because of the generation of 1,2-di-p-tolyldiazene
from unreacted toluidine, consumption of toluidine continued
for up to 10 h. The product formation profile has been shown in
Figure S2 and the decay of amine in Figure S3. Since two
molecules of 2-phenylacetophenone are involved in the reaction
(Scheme S6), a second-order dependence with respect to 2-
phenylacetophenone was observed.
[27] a) S. Fukuzumi, K. D. Karlin, Coord. Chem. Rev. 2013, 257, 187;
b) E. A. Lewis, W. B. Tolman, Chem. Rev. 2004, 104, 1047;
c) L. M. Mirica, X. Ottenwaelder, T. D. P. Stack, Chem. Rev.
2004, 104, 1013; d) D. Maiti, H. C. Fry, J. S. Woertink, M. A.
Vance, E. I. Solomon, K. D. Karlin, J. Am. Chem. Soc. 2007, 129,
264; e) D. Maiti, D. H. Lee, K. Gaoutchenova, C. Wurtele, M. C.
Holthausen, A. A. N. Sarjeant, J. Sundermeyer, S. Schindler,
K. D. Karlin, Angew. Chem. 2008, 120, 88; Angew. Chem. Int. Ed.
2008, 47, 82; f) A. N. Campbell, S. S. Stahl, Acc. Chem. Res. 2012,
45, 851 – 863; g) Z. Shi, C. Zhang, C. Tang, N. Jiao, Chem. Soc.
Rev. 2012, 41, 3381 – 3430; h) C. Zhang, C. Tang, N. Jiao, Chem.
Soc. Rev. 2012, 41, 3464 – 3484; i) A. E. Wendlandt, A. M. Suess,
S. S. Stahl, Angew. Chem. 2011, 123, 11256 – 11283; Angew.
Chem. Int. Ed. 2011, 50, 11062 – 11087.
[28] C. Zhang, N. Jiao, J. Am. Chem. Soc. 2010, 132, 28 – 29.
[29] D. P. Bauer, R. S. Macomber, J. Org. Chem. 1975, 40, 1990 – 1992.
[30] a) J. Hine, H. W. Haworth, J. Am. Chem. Soc. 1958, 80, 2274 –
2275; b) G. E. Inglett, G. F. Smith, J. Am. Chem. Soc. 1950, 72,
842 – 844; c) M. V. Bhatt, Tetrahedron 1964, 20, 803 – 821; d) W.
Mathes, W. Sauermilch, Chem. Ber. 1953, 86, 109 – 110; e) C. M.
Comisar, P. E. Savage, Green Chem. 2005, 7, 800 – 806.
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