An umpolung strategy for the synthesis of β-aminoketones via copper-catalyzed electrophilic amination of cyclopropanols

Article abstract of DOI:10.1021/acs.orglett.5b00828

A novel copper-catalyzed electrophilic amination of cyclopropanols with O-benzoyl-N,N-dialkylhydroxylamines to synthesize various β-aminoketones via a sequence that includes C-C bond cleavage and C_sp3-N bond formation is reported. The reaction conditions are mild and tolerate a wide range of functional groups including benzoate, tosylate, expoxide, and α,β-unsaturated carbonyls, which are incompatible in the traditional amine nucleophilic conjugate addition and the Mannich reaction conditions. Preliminary mechanistic studies and a proposed catalytic cycle of this umpolung β-aminoketone synthesis process have been described as well.

Full text of DOI:10.1021/acs.orglett.5b00828

Letter
pubs.acs.org/OrgLett
An Umpolung Strategy for the Synthesis of β‑Aminoketones via
Copper-Catalyzed Electrophilic Amination of Cyclopropanols
Zhishi Ye and Mingji Dai*
Department of Chemistry and Center for Cancer Research, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907,
United States
S
* Supporting Information
ABSTRACT: A novel copper-catalyzed electrophilic amination of cyclopropanols
with O-benzoyl-N,N-dialkylhydroxylamines to synthesize various β-aminoketones via
3
a sequence that includes C−C bond cleavage and Csp −N bond formation is
reported. The reaction conditions are mild and tolerate a wide range of functional
groups including benzoate, tosylate, expoxide, and α,β-unsaturated carbonyls, which
are incompatible in the traditional amine nucleophilic conjugate addition and the
Mannich reaction conditions. Preliminary mechanistic studies and a proposed
catalytic cycle of this umpolung β-aminoketone synthesis process have been
described as well.
itrogen-containing groups are indispensable moieties of
inflammatory and neuropathic pain8 prompted us to develop an
Npharmaceuticals, agrochemicals, and materials. Transi- efficient copper-catalyzed electrophilic amination9 of cyclo-
propanols to synthesize various β-aminoketones.10 These
1
2
tion-metal-catalyzed Csp −N bond formations, particularly the
Buchwald−Hartwig amination,2 Chan−Lam coupling,3 and
compounds are commonly prepared by the conjugate addition
of amine nucleophiles to α,β-unsaturated carbonyls11 or the
4
2
Csp −H amination, have significantly advanced the installation
Mannich-type reactions between azomethines and enolates.12
of nitrogen-containing groups on aromatic and olefinic
3
Cyclopropanols are important and useful functional groups
in organic synthesis and can be readily prepared via the
Kulinkovich protocol or cyclopropanation (Simmons−Smith
reaction) of enol ethers.13 Currently, most of the transition-
metal-catalyzed cyclopropanol homoenolate chemistry focus on
palladium-catalyzed C−C bond formation at the β-position.14
Copper-promoted or copper-catalyzed cyclopropanol ring-
opening cross-coupling reactions have been very rare despite
the low-cost and sustainable feature of copper catalysts.15 Ryu,
Murai, and co-workers have discovered that Cu(II)-homo-
enolates derived from the treatment of 1-alkoxy-1-siloxycyclo-
propanes with a stoichiometric amount Cu(BF4)2 could
undergo homodimerziation to form 1,6-diketones or be trapped
by highly electron-deficient acetylenes to form cross-coupling
products.16 Recently, Cha, and co-workers have developed
elegant SN2′ alkylations of the metallo-homoenolate derived
from treating cyclopropanols with more than a stoichiometric
amount of CuCN and 1 equiv of ZnEt2 as well as their
applications in complex natural product synthesis.17
substrates. However, transition-metal-catalyzed Csp −N bond
formation at nonactivated Csp -centers for the syntheses of
3
aliphatic amines are still very limited. Significant advances in
5
6
3
Csp −H amination reaction and amination of double bond
have been made recently to synthesize aliphatic nitrogen-
containing compounds. Our interest in using cyclopropanols
and the related systems as useful alkyl cross-coupling partners
to form important Csp −Csp and Csp −heteroatom bonds
(Figure 1A and 1B)7 as well as using polysubstituted amines as
potential selective adenylyl cyclase 1 inhibitors for treating
3
3
3
Electrophilic ring-opening amination of cyclopropanols could
provide an umpolung and complementary strategy to
synthesize β-amino carbonyls. We hypothesized that a Cu(I)
catalyst could be oxidized to Cu(III) by an O-benzoyl-N,N-
dialkylhydroxylamine18 (cf. 2, Figure 1C); the resulting Cu(III)
species would promote a cyclopropanol ring-opening reaction
Figure 1. Our general hypothesis and work on copper-catalyzed ring-
opening cross-coupling reactions.
Received: March 20, 2015
Published: April 17, 2015
© 2015 American Chemical Society
2190
DOI: 10.1021/acs.orglett.5b00828
Org. Lett. 2015, 17, 2190−2193

Organic Letters
Letter
to generate copper-homoenolate 3, which would undergo
3
reductive elimination to form a Csp −N bond and regenerate
the Cu(I) catalyst. We were also hoping that the use of a
catalytic amount of a copper catalyst and the close interaction
between the NR1R2 group and the copper-homoenolate could
potentially suppress the homocoupling, further oxidation, and
other undesired reaction pathways. Herein, we report the first
copper-catalyzed electrophilic amination of cyclopropanols with
O-benzoyl-N,N-dialkylhydroxylamines.
Our exploration started with model substrates 1a and 2a
(Table 1). When a mixture of 1a and 2a were treated with a
Table 1. Reaction Condition Optimization
a
entry
Cu cat.
solvent
THF
temp (°C)
yield (%)
b
1
CuI
80
80
80
80
80
80
80
rt
85
2
CuI
THF
88
75
65
82
90
0
3
CuI
toluene
DCE
4
CuI
5
CuI
1,4-dioxane
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
6
CuI
7
−
CuI
8
39
93
88
98
9
CuI
50
50
50
50
50
50
Figure 2. Cyclopropanol substrate scope. a Yield of isolated products.
10
11
12
13
14
CuCl
CuBr
CuBr
CuBr
CuBr
b Gram-scale reaction.
b
93
c
80
d
trace
a
General reaction conditions: A solution of 1a (0.15 mmol), 2a (0.1
mmol), and Cu(I) catalyst (0.1 equiv) were stirred until no more
starting material remained. The reaction process was monitored by
thin-layer chromatography. Isolated yield from flash chromatography
b
c
was given. 1/1 of 1a/2a (0.1 mmol). 1a (0.1 mmol) and 2a (0.15
d
mmol). Phenanthroline (0.1 equiv).
catalytic amount of CuI (0.1 equiv) in THF at 80 °C, the
desired β-morpholinylketone 4a was produced in 85% yield.
Further reaction condition optimization showed that (i) MeCN
is superior to other solvents such as THF, toluene, DCE, and
1,4-dioxane presumably due to its coordinating capacity with
the copper catalyst and (ii) CuBr works slightly better than
CuCl and CuI. The reaction proceeds efficiently at 50 °C, but
the yield dropped significantly when the reaction was
conducted at room temperature. Increasing the amount of 2a
to 1.5 equiv gave a reduced reaction yield, while using 1.5 equiv
of 1a was beneficial for the production of 4a. Nitrogen-based
bidentate ligand phenanthroline inhibited the product for-
mation. Overall, we were able to obtain β-morpholinylketone
4a in 98% yield with CuBr (0.1 equiv) in MeCN at 50 °C
(entry 11).
With the optimized reaction conditions, we then investigated
the substrate scope of this electrophilic β-amination process in
terms of both cyclopropanols (Figure 2) and O-benzoyl-N,N-
dialkylhydroxylamines (Figure 3). To our satisfaction, both aryl
and alkyl substituted cyclopropanols underwent the desired
ring-opening cross-coupling reaction to provide various aryl
and alkyl β-aminoketones, respectively, in good to excellent
yield. Ether (4a and 4h), bromide (4b), fluoride (4c),
cyclopropyl (4f), TBS-ether (4k and 4q), terminal olefin
Figure 3. O-Benzoyl-N,N-dialkylhydroxylamine scope. a Yield of
isolated products. b 80 °C.
(4p), free alcohol (4j), and diene (4r) functional groups are
well tolerated under the reaction conditions. Notably, func-
tional groups such as enone (4i), benzoate (4l), tosylate (4m),
epoxide (4n), and α,β-unsaturated ester (4o), which pose
potential compatibility problems under the conventional
2191
DOI: 10.1021/acs.orglett.5b00828
Org. Lett. 2015, 17, 2190−2193

Organic Letters
Letter
nucleophilic conjugate amine addition conditions as well as the
Mannich reaction conditions to synthesize β-amino ketones,
survived the mild electrophilic amination conditions very well.
In addition to O-benzoyl-morpholine (2a), many other O-
benzoyl-N,N-dialkylhydroxylamines work smoothly as the
nitrogen-containing group donors (Figure 3). Benzyl (5a and
5b), allyl (5d), sulphonamide (5h), Boc-carbamate (5i and 5l),
urea (5j), and amide (5k) groups are compatible with the
reaction conditions. Notably, azitidine (5f), azepane (5g), 1,4-
diazepane (5h), piperazine (5i−k), and indole or tryptoline
(5m)-containing β-aminoketones could be obtained in good to
excellent yields. The reaction could be conducted in gram scale
as well (4a, Figure 2).
We then started to probe the reaction mechanism. When the
reaction was conducted in the absence of O-benzoyl-N,N-
dialkylhydroxylamines, only a trace amount of ring opened
product 6 was produced from 1a (Figure 4, eq 1). Increasing
Figure 5. Proposed catalytic cycle.
3
C. Reductive elimination would form the desired Csp −N bond,
produce β-aminoketone 4/5, and regenerate the Cu(I) catalyst.
In summary, we have developed a novel copper-catalyzed
electrophilic amination of cyclopropanols with O-benzoyl-N,N-
dialkylhydroxylamines as an oxidant. Various β-aminoketones
can be synthesized in good to excellent yield. This novel
synthetic transformation features mild reaction conditions, a
broad substrate scope, and excellent functional group
compatibility, particularly those functional groups that are
problematic under the traditional nucleophilic conjugate
addition conditions and the Mannich reaction conditions.
The reaction can also be conducted on gram scale. Preliminary
mechanism studies have been conducted and led us to propose
a Cu(I)/Cu(III) catalytic cycle to account for the observed
outcomes. While further mechanistic investigations are
necessary to understand this reaction, it does open a new
gate for the development of novel synthetic transformations
3
involving the use of cyclopropanols and related systems as Csp
cross-coupling partners.
Figure 4. Preliminary probe of reaction mechanisms.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and characterization for new com-
pounds are provided. This material is available free of charge via
the Internet at http://pubs.acs.org.
the amount of CuBr to 1.0 equiv resulted in a 17/1 ratio of 1a/
6. These results indicate that CuBr alone is not effective enough
to induce a cyclopropanol ring opening and a higher oxidation
level of copper catalyst, Cu(II) or Cu(III), is required. When
O-benzoyl-N,N-dialkylhydroxylamine 2o was employed, desired
product 5o was obtained in 69% yield and we did not observe
the formation of pyrrolidine product 7 (Figure 4, eq 2), which
suggests that a nitrogen radical is not likely involved during the
oxidation of the Cu(I) catalyst. Similarly, cyclopropanol 1s gave
desired product 4s in 76% yield and no cyclized product 8 was
isolated indicating a nonradical cyclopropanol ring-opening
process (Figure 4, eq 3).19 These two notions are further
supported by the insensitivity of the reaction to the addition of
1.0 equiv of TEMPO (Figure 4, eq 4).
With these preliminary experimental results, we proposed the
following reaction mechanism based on a Cu(I)/Cu(III)
catalytic cycle (Figure 5). The Cu(I) catalyst was first oxidized
to Cu(III) complex A by O-benzoyl-N,N-dialkylhydroxylamine
2.20 The latter would undergo ligand exchange and coordinate
with cyclopropanol 1 to produce intermediate B, which then
underwent β-carbon elimination to open the cyclopropane ring
by breaking the Walsh bond and provide Cu(III) homoenolate
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: mjdai@purdue.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Prof. Y. Xia’s group at Purdue University for
assistance with mass spectrometry and Purdue University for
startup support. The NIH for supporting shared NMR
resources to the Purdue Center for Cancer Research is
acknowledged (P30CA023168). This work is also partially
supported by the ACS Petroleum Research Foundation (PRF#
54896-DNI1).
REFERENCES
■
(1) For a review, see: Bariwal, J.; Van der Eycken, E. Chem. Soc. Rev.
2013, 42, 9283.
2192
DOI: 10.1021/acs.orglett.5b00828
Org. Lett. 2015, 17, 2190−2193

Organic Letters
Letter
(2) (a) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem. Soc.
1996, 118, 7215. (b) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc.
1996, 118, 7217.
(3) For selected reviews, see: (a) Ley, S. V.; Thomas, A. W. Angew.
Chem., Int. Ed. 2003, 42, 5400. (b) Qiao, J. X.; Lam, P. Y. S. Synthesis
2011, 829.
B. B.; Das, P. P.; Niocel, M.; Cha, J. K. Org. Lett. 2013, 15, 1780.
(i) Cheng, K.; Walsh, P. J. Org. Lett. 2013, 15, 2298. (j) Rosa, D.;
Orellana, A. Chem. Commun. 2013, 49, 5420. (k) Nithiy, N.; Orellana,
A. Org. Lett. 2014, 16, 5854. (l) Nikolaev, A.; Nithiy, N.; Orellana, A.
Synlett 2014, 2301.
(15) Krause, N. Modern Organocopper Chemistry; Wiley: Hoboken,
NJ, 2002.
(4) For selected reviews, see: (a) Engle, K. M.; Mei, T.-S.; Wang, X.;
Yu, J.-Q. Angew. Chem., Int. Ed. 2011, 50, 1478. (b) Thirunavukkarasu,
V. S.; Kozhushkov, S. I.; Ackermann, L. Chem. Commun. 2014, 50, 29.
For leading references, see: (c) Whitfield, S. R.; Sanford, M. S. J. Am.
Chem. Soc. 2007, 129, 15142. (d) Tan, Y.; Hartwig, J. F. J. Am. Chem.
Soc. 2010, 132, 3676. (e) Kawano, T.; Hirano, K.; Satoh, T.; Miura, M.
J. Am. Chem. Soc. 2010, 132, 6900. (f) Kim, J. Y.; Park, S. H.; Ryu, J.;
Cho, S. H.; Kim, S. H.; Chang, S. J. Am. Chem. Soc. 2012, 134, 9110.
(g) McDonald, S. L.; Hendrick, C. E.; Wang, Q. Angew. Chem., Int. Ed.
2014, 53, 4667. (h) Zhu, D.; Yang, G.; He, J.; Chu, L.; Chen, G.;
Gong, W.; Chen, K.; Eastgate, M. D.; Yu, J.-Q. Angew. Chem., Int. Ed.
2015, 54, 2497.
(5) For selected reviews, see: (a) Hili, R.; Yudin, A. K. Nat. Chem.
Biol. 2006, 2, 284. (b) Davies, H. M. L.; Manning, J. R. Nature 2008,
451, 417. (c) Roizen, J. L.; Harvey, M. E.; DuBois, J. Acc. Chem. Res.
2012, 45, 911. (d) Jeffrey, J. L.; Sarpong, R. Chem. Sci. 2013, 4, 4092.
(e) Wu, X.; Zhao, Y.; Zhang, G.; Ge, H. Angew. Chem., Int. Ed. 2014,
53, 3706.
(16) (a) Ryu, I.; Ando, M.; Ogawa, A.; Murai, S.; Sonoda, N. J. Am.
Chem. Soc. 1983, 105, 7192. (b) Ryu, I.; Matsumoto, K.; Kameyama,
Y.; Ando, M.; Kusumoto, N.; Ogawa, A.; Kambe, N.; Murai, S.;
Sonoda, N. J. Am. Chem. Soc. 1993, 115, 12330.
(17) (a) Das, P. P.; Belmore, K.; Cha, J. K. Angew. Chem., Int. Ed.
2012, 51, 9517. (b) Rao, N. N.; Parida, B. B.; Cha, J. K. Org. Lett.
2014, 16, 6208. (c) Rao, N. N.; Cha, J. K. J. Am. Chem. Soc. 2015, 137,
2243.
(18) (a) Berman, A. M.; Johnson, J. S. J. Am. Chem. Soc. 2004, 126,
5680. (b) Berman, A. M.; Johnson, J. S. J. Org. Chem. 2005, 70, 364.
(c) Berman, A. M.; Johnson, J. S. J. Org. Chem. 2006, 71, 219.
(d) Campbell, M. J.; Johnson, J. S. Org. Lett. 2007, 9, 1521.
(e) Berman, A. M.; Johnson, J. S. Synlett 2005, 1799. (f) Matsuda, N.;
Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2012, 51, 3642.
(g) Matsuda, N.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int.
Ed. 2012, 51, 11827. (h) Rucker, R. P.; Whittaker, A. M.; Dang, H.;
Lalic, G. Angew. Chem., Int. Ed. 2012, 51, 3953. (i) Xiao, Q.; Tian, L.
M.; Tan, R.; Xia, Y.; Qiu, D.; Zhang, Y.; Wang, J. Org. Lett. 2012, 14,
4230. (j) Dumas, A. M.; Molander, G. A.; Bode, J. W. Angew. Chem.,
Int. Ed. 2012, 51, 5683. (k) Mlynarski, S. N.; Karns, A. S.; Morken, J.
P. J. Am. Chem. Soc. 2012, 134, 16449. (l) Dong, Z.; Dong, G. J. Am.
Chem. Soc. 2013, 135, 18350. (m) McDonald, S. L.; Wang, Q. Angew.
Chem., Int. Ed. 2014, 53, 1867. (n) McDonald, S. L.; Wang, Q. Chem.
Commun. 2014, 50, 2535.
(19) For Cu(II) salt-promoted radical cyclopropanol ring opening,
see: (a) Hasegawa, E.; Tateyama, M.; Nagumo, R.; Tayama, E.;
Iwamoto, H. Beilstein J. Org. Chem. 2013, 9, 1397. (b) Hasegawa, E.;
Yamaguchi, N.; Muraoka, H.; Tsuchida, H. Org. Lett. 2007, 9, 2811.
(c) Li, L.-Z.; Xiao, B.; Guo, Q.-X.; Xue, S. Tetrahedron 2006, 62, 7762.
(d) Snider, B. B.; Kwon, T. J. Org. Chem. 1992, 57, 2399. For leading
references for other radical cyclopropanol ring-opening chemistry:
(e) Wang, Y.-F.; Toh, K. K.; Ng, E. P. J.; Chiba, S. J. Am. Chem. Soc.
2011, 133, 6411. (f) Zhao, H.; Fan, X.; Yu, J.; Zhu, C. J. Am. Chem.
Soc. 2015, 137, 3490.
(6) For a review, see: (a) Muller, T. E.; Hultzsch, K. C.; Yus, M.;
̈
Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795. For selected
examples, see: (b) Rucker, R. P.; Whittaker, A. M.; Dang, H.; Lalic, G.
J. Am. Chem. Soc. 2012, 134, 6571. (c) Liu, G.-S.; Zhang, Y.-Q.; Yuan,
Y.-A.; Xu, H. J. Am. Chem. Soc. 2013, 135, 3343. (d) Lu, D.-F.; Zhu, C.-
L.; Jia, Z.-X.; Xu, H. J. Am. Chem. Soc. 2014, 136, 13186.
(e) Niljianskul, N.; Zhu, S.; Buchwald, S. L. Angew. Chem., Int. Ed.
2015, 54, 1638. (f) Sakae, R.; Hirano, K.; Satoh, T.; Miura, M. Angew.
Chem., Int. Ed. 2015, 54, 613. (g) Matsuda, N.; Hirano, K.; Satoh, T.;
Miura, M. J. Am. Chem. Soc. 2013, 135, 4934.
(7) Li, Y.; Ye, Z.; Bellman, T. M, Chi, T.; Dai M. Org. Lett. 2015, 17,
DOI: 10.1021/acs.orglett.5b00782.
(8) Ye, Z.; Brust, T. F.; Watts, V. J.; Dai, M. Org. Lett. 2015, 17, 892.
(9) For reviews, see: (a) Erdik, E.; Ay, M. Chem. Rev. 1989, 89, 1947.
(b) Dembeck, P.; Seconi, G.; Ricci, A. Chem.Eur. J. 2000, 6, 1281.
(c) Barker, T. J.; Jarvo, E. R. Synthesis 2011, 3954. (d) Zhang, M.;
Zhang, A. Synthesis 2012, 1. (e) Corpet, M.; Gosmini, C. Synthesis
2014, 2258. For selected examples: (f) He, C.; Chen, C.; Cheng, J.;
Liu, C.; Liu, W.; Li, Q.; Lei, A. Angew. Chem., Int. Ed. 2008, 47, 6414.
(g) Liu, S.; Liebeskind, L. S. J. Am. Chem. Soc. 2008, 130, 6918.
(h) Barker, T. J.; Jarvo, E. R. J. Am. Chem. Soc. 2009, 131, 15598.
(i) Barker, T. J.; Jarvo, E. R. Angew. Chem., Int. Ed. 2011, 50, 8325.
(j) Ortiz, G. X., Jr.; Kang, B.; Wang, Q. J. Org. Chem. 2014, 79, 571.
(k) Hendrick, C. E.; Wang, Q. J. Org. Chem. 2015, 80, 1059.
(10) (a) Kobayashi, S.; Mori, Y.; Fossey, J. S.; Salter, M. M. Chem.
Rev. 2011, 111, 2626. (b) Cardillo, G.; Tomasini, C. Chem. Soc. Rev.
1996, 25, 117.
(20) (a) Zhu, S.; Niljianskul, N.; Buchwald, S. L. J. Am. Chem. Soc.
2013, 135, 15746. (b) Zhu, S.; Buchwald, S. L. J. Am. Chem. Soc. 2014,
136, 15913. (c) Shi, S.-L.; Buchwald, S. L. Nat. Chem. 2015, 7, 38.
(d) Vikse, K. L.; Chen, P. Organometallics 2015, DOI: 10.1021/
acs.organomet.5b00038. (e) Casitas, A.; Ribas, X. Chem. Sci. 2013, 4,
2301.
(11) For a review, see: Liu, M.; Sibi, M. P. Tetrahedron 2002, 58,
7991.
(12) For reviews, see: (a) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999,
99, 1069. (b) Arend, M.; Westermann, B.; Risch, N. Angew. Chem., Int.
Ed. 1998, 37, 1044. (c) Hart, D. J.; Ha, D.-C. Chem. Rev. 1989, 89,
1447.
(13) For reviews, see: (a) Gibson, D. H.; DePuy, C. H. Chem. Rev.
1974, 74, 605. (b) Ryu, I.; Murai, S. Houben-Weyl Methods of Organic
Chemistry; Thieme: Stuttgart, 1997; Vol. E17c, p 1985. (c) Kulinkovich,
O. G. Chem. Rev. 2003, 103, 2597.
(14) (a) For a review, see: Rosa, D.; Nithiy, N.; Orellana, A.
Synthesis 2013, 3199. For examples, see: (b) Aoki, S.; Fujimura, T.;
Nakamura, E.; Kuwajima, I. J. Am. Chem. Soc. 1988, 110, 3296.
(c) Fujimura, T.; Aoki, S.; Nakamura, E. J. Org. Chem. 1991, 56, 2809.
(d) Aoki, S.; Nakamura, E. Synlett 1990, 741. (e) Kang, S.-K.;
Yamaguchi, T.; Ho, P.-S.; Kim, W.-Y.; Yoon, S.-K. Tetrahedron Lett.
1997, 38, 1947. (f) Rosa, D.; Orellana, A. Org. Lett. 2011, 13, 110.
(g) Rosa, D.; Orellana, A. Chem. Commun. 2012, 48, 1922. (h) Parida,
2193
DOI: 10.1021/acs.orglett.5b00828
Org. Lett. 2015, 17, 2190−2193