Catalyst-Free Transamidation of Aromatic Amines with Formamide Derivatives and Tertiary Amides with Aliphatic Amines

Article abstract of DOI:10.1021/acs.orglett.8b03542

A simple catalyst- and promoter-free protocol has been developed for the transamidation of weakly nucleophilic aromatic amines with formamide derivatives and low-reactivity tertiary amides with aliphatic amines. This strategy is advantageous because no catalyst or promoters are needed, no additives are required, separation and purification is easy, and the reaction is scalable. Significantly, this strategy was further applied to synthesize several pharmaceutical molecules on a gram scale, and excellent yields were achieved.

Full text of DOI:10.1021/acs.orglett.8b03542

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Catalyst-Free Transamidation of Aromatic Amines with Formamide
Derivatives and Tertiary Amides with Aliphatic Amines
Jiawen Yin,‡ Jingyu Zhang,‡ Changqun Cai, Guo-Jun Deng, and Hang Gong*
The Key Laboratory for Green Organic Synthesis and Application of Hunan Province; The Key Laboratory of Environmentally
Friendly Chemistry and Application of the Ministry of Education College of Chemistry, Xiangtan University, Xiangtan 411105,
China
S
* Supporting Information
ABSTRACT: A simple catalyst- and promoter-free protocol has been
developed for the transamidation of weakly nucleophilic aromatic
amines with formamide derivatives and low-reactivity tertiary amides
with aliphatic amines. This strategy is advantageous because no
catalyst or promoters are needed, no additives are required, separation
and purification is easy, and the reaction is scalable. Significantly, this
strategy was further applied to synthesize several pharmaceutical molecules on a gram scale, and excellent yields were achieved.
he amide framework is an important building block of
transamidation is attractive because it is a convenient,
economic, and efficient protocol.8a,14
T
protein, which is known as the “first substance of life”.1
Amides are also applied as versatile intermediates in synthetic
chemistry, and are widely present in pharmaceuticals,2
pesticides,3 natural products,4 and other functional materials
(Figure 1).5 In 2007, “amide formation avoiding poor atom
Over time, great advances in transamidation have been made
by numerous groups. However, because of the stability of the
amide bond, these reactions usually proceed in the presence of
various catalysts or activating agents. Most of the developed
transamidation reactions are based on methods that utilize a
catalyst that is a metal, such as Pd,15a,b Ni,15c,d Fe,15e Cu,15f
Mn,15g Sc,15h Hf,15i lanthanides,15j Ti,15h,k Ce,15l,m Zr,15n,o
Nb,15p Al,15q,r and sulfated tungstate.15s (Scheme 1A) Metal
residues must be carefully avoided during the synthesis of
pharmaceuticals, because of the toxicity of metal in
pharmaceutical molecules. In addition, metal-catalyzed reac-
tions are undesirable, because of the waste of metal resources
and increase in synthetic cost. Subsequently, various metal-free
methods involving the use of ammonium salts,16a,b N,N-
dialkylformamide dimethyl acetals,16c boric acid deriva-
tives,16d−g chitosan,16h L-proline,16i imidazole derivatives,16j,k
hypervalent iodine,16l benzotriazole,16m and NEt3,16n as well as
microwave irradiation processes,16o,p have been developed
(Scheme 1B). Although these metal-free protocols possess
certain advantages, some deficiencies still exist, such as using
stoichiometric catalysts, difficulties with separation catalysts,
and poor selectivity. It is worthy of special attention that these
metal-free protocols are usually limited to active primary
amides reacting with aliphatic amines. Therefore, the
challenges of transamidation of weakly nucleophilic aromatic
amines with amides and low reactivity tertiary amides with
amines under metal-free, even catalyst-free, conditions, are still
retained.
Figure 1. Amide frameworks in bioactive substances and functional
materials.
economy reagents” was designated as the top challenging topic
of synthetic chemistry by the American Chemical Society
Green Chemistry Institute Pharmaceutical Roundtable (ACS
GCIPR).6 Moreover, the amide framework is present in ∼25%
of pharmaceuticals, indicating its special role in synthetic
chemistry.7 Hence, there has been increasing interest in the
synthesis of amides, and many new synthetic strategies have
been developed.8 Conventionally, amides were synthesized by
the coupling of amines with carboxylic acids derivatives,9
aldehydes,10 or alcohols.11 However, the drawbacks of these
methods are large consumption of Lewis acid/base, poor
atomic utilization, use of toxic substances or generation of toxic
waste, and difficulties in separation and purification.8−12 Thus,
various alternative methods for the synthesis of amides were
developed to overcome these deficiencies.13 Among them, the
The widely accepted mechanism of transamidation is shown
in Scheme 1C, in which the key step is the activation of
carbonyl on an amide by a catalyst, resulting in the following
Received: November 5, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03542
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 1. Reported Transamidation, Mechanism, and Our
Assumption: (A) Metal-Catalyzed Reaction, (B) Metal-Free
Reaction, (C) Accepted Mechanism, (D) Proposed Catalyst-
Free Mechanism, and (E) Catalyst-Free Reaction (This
Work)
Scheme 2. Screen of Formyl Source
a
Unless otherwise noted, all reactions were conducted in a sealed tube
under an air atmosphere. 1 mmol amine, 10 equiv of amide. bReaction
time = 72 h.
a
Table 1. Optimization Experiments
nucleophilic process occurring with ease. Thus, we assumed
that the hydrogen in the amine might form the hydrogen bond
with the carbonyl group of the amide and activate the carbonyl
group (Scheme 1D). Our previous work confirmed this
assumption.17 It was found the transamidation reaction could
be achieved with a yield of 27%, using aliphatic amines and
dimethylformamide (DMF) as reactants in the absence of
catalyst.
Yield (%)
entry
temperature (°C)
time, t (h)
2a
3a
1a
1
2
3
4
5
6
7
8
150
150
150
150
150
150
150
130
12
12
12
12
12
15
24
24
10
8
5
3
1
10
10
10
85
79
72
56
48
87
92
82
12
20
27
41
36
14
7
Based on these considerations and previous work,17 herein,
we utilized the properties of reactants to realize catalyst-free
transamidation. Our focus is on the development of a catalyst-
free protocol for the transamidation of weak nucleophilic
aromatic amines with formamide derivatives to construct N-
arylcarboxamides. In addition, the transamidation of aliphatic
amines with low reactivity tertiary amides was also investigated
under these catalyst-free conditions (Scheme 1E).
18
a
Unless otherwise noted, all reactions were conducted on in a sealed
tube under air. NMR yield (CH3NO2 as an internal standard).
After determining the most optimizal conditions, the
transamidation of various aromatic amines and formamide
was investigated (Scheme 3). The reaction proceeded well
when using aniline with electron-donating groups as substrates,
such as alkyl, alkoxy, amino, and phenyl (3a−3m). When 4-
aminophenol (1l) was used, an oxidation side reaction
occurred and only a moderate yield of 57% was obtained.
Then, this experiment was conducted under an atmosphere of
argon, and an expected excellent yield of transamidation
product was achieved (3l, 99%). Halogenated aniline also
could be transferred to the desired product with good to
excellent yield (3n−3q). When aromatic diamines were used
as the substrate, the dihydroformylation proceeded with
excellent yield (3r). No benefit to the reaction was observed
when strong electron-withdrawing groups existed on aniline,
and only a poor to moderate yield could be achieved (3s, 3u−
3w). However, the 3-nitroaniline and 4-(trifluoromethoxy)-
aniline could be transferred to the hydroformylation product
with good yield (3t, 3x). Polycyclic aromatic amines were
obtained using this reaction with good to excellent yields when
First, several formamide derivatives were screened to select a
suitable formyl source. The results show that small hindrance
formamide produces the best yield (Scheme 2, entry 1). The
hindrance of substituents on nitrogen confers an obvious effect
during this transformation. Other N-monosubstituted for-
mamides give moderate to good yields (Scheme 2, entries 2−
5); however, for the N,N-disubstituted formamide, only a poor
yield of 26% could be obtained (Scheme 2, entry 6).
Then, the reaction conditions were optimized by using
formamide as a formyl source (Table 1). The transamidation
product was obtained with good yield (85%) when 10 equiv of
formamide was used (Table 1, entry 1). However, the yield
was decreased as the amount of formamide was reduced, which
may have occurred because of the low efficiency of the mass
transfer (Table 1, entries 2−5). The most optimal result was
found when using 10 equiv of formamide as the formyl source,
and extending the reaction time to 24 h (Table 1, entry 7).
When the temperature was decreased, the yield was reduced
(Table 1, entry 8).
B
DOI: 10.1021/acs.orglett.8b03542
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Organic Letters
Letter
a
a
Scheme 3. Substrate Scope of Aromatic Amines
Scheme 4. Substrate Scope of Amides
a
Unless otherwise noted, all reactions were conducted on a 1.0 mmol
scale, 10 equiv of amide, in a sealed tube under air for 24 h. Isolated
b
yield. 2.0 equiv of DMA was added.
no product was obtained. These results indicated that there is
the potential for this catalyst-free strategy to have the potential
to extend to N-acylation using different alkylamides, even using
polyhalogen-containing alkylamides as acyl sources. When the
transamidation was conducted with aromatic amines and
DMF, only poor yield was obtained, because of the hindrance
of DMF (Scheme 2, entry 6). We then suspected that if highly
active amines were used instead of aromatic amines, a higher
yield might be obtained. Various aliphatic amines were then
examined under modified conditions: aliphatic amine on a 1.0
mmol scale in a sealed tube under an atmosphere of argon. As
expected, a high yield was obtained whenever a primary amine
or secondary amine was used as the substrate (Scheme 5, 3A−
3T). In addition, the reaction of chiral amino acid ester and
DMF also could occur, but only a poor yield of racemized
product could be obtained (Scheme 5, 3U). The poor yield
might be caused by the poor solubility of amino acid ester in
DMF, and the racemization might be caused by the high
reaction temperature. Moreover, if formamide is used instead
of DMF, a moderate yield of 58% could be found (Scheme 5,
3U).
Importantly, the simplicity of this catalyst-free strategy to
access amide can be easily scaled to the gram-level with an
excellent yield of 98% (Scheme 6A). In particular,
acetaminophen,2a which is a widely used anodyne drug, can
be effectively achieved from p-aminophenol on a gram scale by
one step with excellent yield (96%). In addition, the
purification operation also can be simplified as an extraction
and washing process to obtain the pure product with exellent
yield of 92% (see the Supporting Information). Compared
with existing methods, our method is particularly significant for
the pharmaceutical industry, because there is no metal residue,
it is catalyst-free and step-saving, a preprotected hydroxy group
is not required, and separation and purification are easy
(Scheme 6B).8c,18 Moreover, acetaminophen can be converted
to the bioactive molecule BMY 30123 with good yield
(Scheme 6C).2c,19 As another indicator of practicability, the
desired product 3M has been used as a marker for the
a
Unless otherwise noted, all reactions were conducted on a 1.0 mmol
scale, amide (10 equiv), in a sealed tube under air for 24 h. Isolated
b
c
d
yield. Reaction time = 48 h. Reaction time = 72 h. Under argon.
eReaction time = 96 h. 0.5 mmol 1za, 10 equiv of formamide.
f
the amine group was located on the α- or β-position (3y−
3zb). This strategy was also applicable for heteroaromatic
amines. When electron-rich heteroaromatic amines were used,
good to excellent yields were obtained (3zc−3ze), whereas, in
the case of electron-poor heteroaromatic amines, a much lower
yield resulted (3zf−3zg). When 3-aminopyridine (1zh) was
used, a result was obtained that was similar to that observed
when 3-nitroaniline (1t) was used, because of the hither
electron density of the meta-position, compared to the ortho-
and para-position. In the case of cyclo aromatic amines, such as
indoline (3zi) and 1,2,3,4-tetrahydroquinoline (3zj), good to
excellent yield could be achieved. However, when open-chain
secondary arylamines and diarylamines were used, only poor to
moderate yields were obtained, because of their larger steric
resistance (3zk−3zn).
To investigate the possibility of extensive N-acylation rather
than N-formylation, other carbonyl sources were examined
(Scheme 4). Delightedly, the N-acetylation and N-propiony-
lation proceeded well by using acetamide and propanamide as
carbonyl sources, and high yields of 83% and 93% were
obtained, respectively (3zo, 3zq). Butyrylation and isobutyla-
tion could be achieved only with moderate yields, because of
the hindrance of alkyl groups (3zq, 3zr). Halogen-containing
carbonyl sources also were tested, and the desired products
were obtained with acceptable yields (3zs, 3zt). However,
when aromatic amides were used as carbonyl sources, almost
C
DOI: 10.1021/acs.orglett.8b03542
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Letter
reported as a precursor for the synthesis of a series of natural
molecules such as pseudopalmatine, 8-oxopseudopalmatine,
and ilicifoline B.21 Finally, the intramolecular competitive
reaction were performed using 4-(aminomethyl)aniline as a
substrate (Scheme 6D). When using DMF as an acyl source, a
good chemoselectivity was found. The transamidation will be
occurred on the aliphatic amino only, even after 72 h.
However, in the case of formamide as the acyl source, two
types of transamidation products would be detected with 77%
yield [N-(4-aminobenzyl)formamide] and 21% yield [N-(4-
formamidobenzyl)formamide] after 10 min of reaction. If the
reaction time was extended to 5 h, the diacylation product
would be found as the sole product, with an excellent yield of
98%. These results indicated that the transamidation is more
likely to occur at the aliphatic amino.
Scheme 5. Transamidation Reactions of Aliphatic Amines
and DMF
a
In summary, the catalyst-free transamidation protocol of
weakly nucleophilic aromatic amines with formamide deriva-
tives and aliphatic amines with low reactivity tertiary amides
was realized by utilizing the properties of the reactants. The
advantages of this protocol are that it is a catalyst-free, metal-
free, additive-free, and scalable, with easy separation and
purification. Particularly, gram-scale preparation of widely used
pharmaceuticals and bioactive molecules was easily performed
via this protocol, which provides a green and environmentally
friendly route for the synthesis of various amides.
a
Unless otherwise noted, all reactions were conducted on a 1.0 mmol
b
ASSOCIATED CONTENT
scale in a sealed tube under argon. Isolated yield. DMF = 2.5 equiv.
■
cAmine = 0.5 mmol, DMF = 5 equiv. dDMF 5 equiv. eL-Phenylalanine
ethyl ester hydrochloride was used as substrate and 1 equiv of
S
* Supporting Information
f
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03542.
Na2CO3 was added. L-Phenylalanine ethyl ester hydrochloride was
used as substrate. and the reaction was performed in 20 equiv of
formamide under air.
Experimental procedures, spectral and analytical data,
Scheme 6. Gram-Scale Reaction and Applications
1
copies of H and 13C NMR spectra for new compounds
(PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: hgong@xtu.edu.cn.
ORCID
Guo-Jun Deng: 0000-0003-2759-0314
Hang Gong: 0000-0003-4513-593X
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Author Contributions
‡These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
Hunan Province (No. 2018JJ2389), National Natural Science
Foundation of China (No. 21402168), and the Project of
Innovation Team of the Ministry of Education (No.
IRT_17R90) for their support of our research.
antidepressant drug fluoxetine.20 Transamidation product 3Q
also can be achieved via this protocol from the natural
molecule homoveratrylamine with good yields, and it has been
D
DOI: 10.1021/acs.orglett.8b03542
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Letter
Friend, C. M. ACS Catal. 2017, 7, 965. (i) Watson, A. J. A.; Maxwell,
A. C.; Williams, J. M. J. Org. Lett. 2009, 11, 2667.
REFERENCES
■
(1) (a) Greenberg, A.; Breneman, C. M.; Liebman, J. F. The Amide
Linkage Structural Significance in Chemistry, Biochemistry, and Materials
Science; Wiley−Interscience: New York, 2000. (b) Larock, R. C.
Comprehensive Organic Transformations, 2nd Edition; Wiley−VCH:
Weinheim, Germany, 1999. (c) Sewald, N.; Jakubke, H. D. Peptides:
Chemistry and Biology; Wiley−VCH: Weinheim, Germany, 2002.
(d) Bray, B. L. Nat. Rev. Drug Discovery 2003, 2, 587. (e) Humphrey,
J. M.; Chamberlin, A. R. Chem. Rev. 1997, 97, 2243.
(2) (a) Larson, A. M.; Polson, J.; Fontana, R. J.; Davern, T. J.; Lalani,
E.; Hynan, L. S.; Reisch, J. S.; Schiødt, F. V.; Ostapowicz, G.; Shakil,
A. O.; Lee, W. M. and the Acute Liver Failure Study Group.
Hepatology 2005, 42, 1364. (b) Hett, R.; Fang, Q. K.; Gao, Y.; Wald,
S. A.; Senanayake, C. H. Org. Process Res. Dev. 1998, 2, 96.
(c) Tramposch, K. M.; Nair, X.; Gendimenico, G. J.; Tetrault, G. B.;
Chen, S.; Kiss, I.; Whiting, G.; Bonney, R. J. J. Pharm. Pharmacol.
1992, 44, 379.
(3) Kniss, A. R. Nat. Commun. 2017, 8, 14865.
(4) Batchelor, F. R.; Doyle, F. P.; Nayler, J. H. C.; Rolinson, G. N.
Nature 1959, 183, 257.
(5) Polyimides Fundamentals and Applications; Ghosh, M. K., Mittal,
K. L., Eds.; Marcel Dekker: New York, 1996.
(6) Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.;
Leazer, J. L., Jr.; Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman, B.
A.; Wells, A.; Zaks, A.; Zhang, T. Y. Green Chem. 2007, 9, 411.
(7) Ghose, A. K.; Viswanadhan, V. N.; Wendoloski, J. J. J. Comb.
Chem. 1999, 1, 55.
(8) (a) Pattabiraman, V. R.; Bode, J. W. Nature 2011, 480, 471.
(b) de Figueiredo, R. M.; Suppo, J.-S.; Campagne, J.-M. Chem. Rev.
2016, 116, 12029. (c) Allen, C. L.; Williams, J. M. J. Chem. Soc. Rev.
2011, 40, 3405. (d) Cheung, C. W.; Ma, J.-A.; Hu, X. J. Am. Chem.
Soc. 2018, 140, 6789. (e) Cheung, C. W.; Ploeger, M. L.; Hu, X. ACS
Catal. 2017, 7, 7092. (f) Aruri, H.; Singh, U.; Kumar, S.; Kushwaha,
M.; Gupta, A. P.; Vishwakarma, R. A.; Singh, P. P. Org. Lett. 2016, 18,
3638.
(9) (a) Takise, R.; Muto, K.; Yamaguchi, J. Chem. Soc. Rev. 2017, 46,
5864. (b) Lundberg, H.; Tinnis, F.; Selander, N.; Adolfsson, H. Chem.
Soc. Rev. 2014, 43, 2714. (c) Valeur, E.; Bradley, M. Chem. Soc. Rev.
2009, 38, 606. (d) Ben Halima, T.; Masson-Makdissi, J.; Newman, S.
(12) (a) Montalbetti, C. A. G. N.; Falque, V. Tetrahedron 2005, 61,
10827. (b) Han, S.-Y.; Kim, Y.-A. Tetrahedron 2004, 60, 2447.
(13) (a) Petchey, M.; Cuetos, A.; Rowlinson, B.; Dannevald, S.;
Frese, A.; Sutton, P. W.; Lovelock, S.; Lloyd, R. C.; Fairlamb, I. J. S.;
Grogan, G. Angew. Chem., Int. Ed. 2018, 57, 11584. (b) Hai, Y.; Tang,
Y. J. Am. Chem. Soc. 2018, 140, 1271. (c) Choi, H.; Shirley, H. J.;
Hume, P. A.; Brimble, M. A.; Furkert, D. P. Angew. Chem., Int. Ed.
2017, 56, 7420. (d) Wood, A. J. L.; Weise, N. J.; Frampton, J. D.;
Dunstan, M. S.; Hollas, M. A.; Derrington, S. R.; Lloyd, R. C.;
Quaglia, D.; Parmeggiani, F.; Leys, D.; Turner, N. J.; Flitsch, S. L.
Angew. Chem., Int. Ed. 2017, 56, 14498. (e) Takeda, N.; Futaki, E.;
Kobori, Y.; Ueda, M.; Miyata, O. Angew. Chem., Int. Ed. 2017, 56,
16342. (f) Huang, B.; Zeng, L.; Shen, Y.; Cui, S. Angew. Chem., Int. Ed.
2017, 56, 4565. (g) Shimoda, Y.; Yamamoto, H. J. Am. Chem. Soc.
2017, 139, 6855. (h) Cheung, C. W.; Leendert Ploeger, M. L.; Hu, X.
Chem. Sci. 2018, 9, 655. (i) Ray, R.; Hazari, A. S.; Chandra, S.; Maiti,
D.; Lahiri, G. K. Chem. - Eur. J. 2018, 24, 1067. (j) Singh, K.;
Sarbajna, A.; Dutta, I.; Pandey, P.; Bera, J. K. Chem. - Eur. J. 2017, 23,
7761. (k) Yu, M.; Zhang, T.; Jalani, H. B.; Dong, X.; Lu, H.; Li, G.
Org. Lett. 2018, 20, 4828. (l) Philpott, H. K.; Thomas, P. J.; Tew, D.;
Fuerst, D. E.; Lovelock, S. L. Green Chem. 2018, 20, 3426. (m) Sayes,
M.; Charette, A. B. Green Chem. 2017, 19, 5060. (n) Cheng, G.; Lv,
W.; Kuai, C.; Wen, S.; Xiao, S. Chem. Commun. 2018, 54, 1726.
(o) Feng, W.-X.; Dai, L.; Zheng, S.-P.; van der Lee, A.; Su, C.-Y.;
Barboiu, M. Chem. Commun. 2018, 54, 9738.
(14) (a) Lanigan, R. M.; Sheppard, T. D. Eur. J. Org. Chem. 2013,
2013, 7453. (b) Muma, N. A.; Mi, Z. ACS Chem. Neurosci. 2015, 6,
961.
(15) (a) Meng, G.; Lei, P.; Szostak, M. Org. Lett. 2017, 19, 2158.
(b) Shi, S.; Szostak, M. Chem. Commun. 2017, 53, 10584. (c) Dander,
J. E.; Baker, E. L.; Garg, N. K. Chem. Sci. 2017, 8, 6433. (d) Sonawane,
R. B.; Rasal, N. K.; Jagtap, S. V. Org. Lett. 2017, 19, 2078. (e) Becerra-
Figueroa, L.; Ojeda-Porras, A.; Gamba-Sanchez, D. J. Org. Chem.
2014, 79, 4544. (f) Zhang, M.; Imm, S.; Bahn, S.; Neubert, L.;
Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2012, 51, 3905.
(g) Singh, D. P.; Allam, B. K.; Singh, K. N.; Singh, V. P. RSC Adv.
2014, 4, 1155. (h) Eldred, S. E.; Stone, D. A.; Gellman, S. H.; Stahl, S.
S. J. Am. Chem. Soc. 2003, 125, 3422. (i) Shi, M.; Cui, S. Synth.
Commun. 2005, 35, 2847. (j) Calimsiz, S.; Lipton, M. A. J. Org. Chem.
2005, 70, 6218. (k) Kissounko, D. A.; Hoerter, J. M.; Guzei, I. A.;
Cui, Q.; Gellman, S. H.; Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 1776.
(l) Tamura, M.; Tonomura, T.; Shimizu, K.; Satsuma, A. Green Chem.
2012, 14, 717. (m) Wang, Y.; Wang, F.; Zhang, C.; Zhang, J.; Li, M.;
Xu, J. Chem. Commun. 2014, 50, 2438. (n) Stephenson, N. A.; Zhu, J.;
Gellman, S. H.; Stahl, S. S. J. Am. Chem. Soc. 2009, 131, 10003.
(o) Atkinson, B. N.; Chhatwal, A. R.; Lomax, H. V.; Walton, J. W.;
Williams, J. M. J. Chem. Commun. 2012, 48, 11626. (p) Ghosh, S. C.;
Li, C. C.; Zeng, H. C.; Ngiam, J. S. Y.; Seayad, A. M.; Chen, A. Adv.
Synth. Catal. 2014, 356, 475. (q) Bon, E.; Bigg, D. C. H.; Bertrand, G.
J. Org. Chem. 1994, 59, 4035. (r) Hoerter, J. M.; Otte, K. M.;
Gellman, S. H.; Cui, Q.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 647.
(s) Pathare, S. P.; Jain, A. K. H.; Akamanchi, K. G. RSC Adv. 2013, 3,
7697.
(16) (a) Allen, C. L.; Atkinson, B. N.; Williams, J. M. J. Angew.
Chem., Int. Ed. 2012, 51, 1383. (b) Shimizu, Y.; Morimoto, H.; Zhang,
M.; Ohshima, T. Angew. Chem., Int. Ed. 2012, 51, 8564. (c) Dineen,
T. A.; Zajac, M. A.; Myers, A. G. J. Am. Chem. Soc. 2006, 128, 16406.
(d) El Dine, T. M.; Evans, D.; Rouden, J.; Blanchet, J. Chem. - Eur. J.
2016, 22, 5894. (e) Nguyen, T. B.; Sorres, J.; Tran, M. Q.;
Ermolenko, L.; Al-Mourabit, A. Org. Lett. 2012, 14, 3202. (f) Starkov,
P.; Sheppard, T. D. Org. Biomol. Chem. 2011, 9, 1320. (g) Lanigan, R.
M.; Starkov, P.; Sheppard, T. D. J. Org. Chem. 2013, 78, 4512.
(h) Nageswara Rao, S.; Chandra Mohan, D.; Adimurthy, S. Green
Chem. 2014, 16, 4122. (i) Rao, S. N.; Mohan, D. C.; Adimurthy, S.
Org. Lett. 2013, 15, 1496. (j) Suchy, M.; Elmehriki, A. A. H.; Hudson,
R. H. E. Org. Lett. 2011, 13, 3952. (k) Chikkulapalli, A.; Aavula, S. K.;
Mona NP, R.; C, K.; C H, V K; Sulur G, M.; Sumathi, S. Tetrahedron
́
G. Angew. Chem., Int. Ed. 2018, 57, 12925. (e) Galvez, A. O.; Schaack,
C. P.; Noda, H.; Bode, J. W. J. Am. Chem. Soc. 2017, 139, 1826.
(f) Zeng, S.; Liu, J.; Anankanbil, S.; Chen, M.; Guo, Z.; Adams, J. P.;
Snajdrova, R.; Li, Z. ACS Catal. 2018, 8, 8856. (g) Arnold, K.; Davies,
B.; Herault, D.; Whiting, A. Angew. Chem., Int. Ed. 2008, 47, 2673.
(h) Ben Halima, T.; Vandavasi, J. K.; Shkoor, M.; Newman, S. G. ACS
Catal. 2017, 7, 2176. (i) Hu, L.; Xu, S.; Zhao, Z.; Yang, Y.; Peng, Z.;
Yang, M.; Wang, C.; Zhao, J. J. Am. Chem. Soc. 2016, 138, 13135.
(j) Gnanaprakasam, B.; Milstein, D. J. Am. Chem. Soc. 2011, 133,
1682. (k) Beutner, G. L.; Young, I. S.; Davies, M. L.; Hickey, M. R.;
Park, H.; Stevens, J. M.; Ye, Q. Org. Lett. 2018, 20, 4218.
(10) (a) Luo, J.; Wei, W.-T. Adv. Synth. Catal. 2018, 360, 2076.
(b) Gusev, D. G. ACS Catal. 2017, 7, 6656. (c) Liu, Z.; Zhang, J.;
Chen, S.; Shi, E.; Xu, Y.; Wan, X. Angew. Chem., Int. Ed. 2012, 51,
3231. (d) Xu, B.; Zhou, L.; Madix, R. J.; Friend, C. M. Angew. Chem.,
Int. Ed. 2010, 49, 394. (e) Yoo, W.-J.; Li, C.-J. J. Am. Chem. Soc. 2006,
128, 13064. (f) Nguyen, T. T.; Hull, K. L. ACS Catal. 2016, 6, 8214.
(g) Ghosh, S. C.; Ngiam, J. S. Y.; Seayad, A. M.; Tuan, D. H.; Chai, C.
L. L.; Chen, A. J. Org. Chem. 2012, 77, 8007.
(11) (a) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007,
317, 790. (b) Kumar, A.; Espinosa-Jalapa, N. A.; Leitus, G.; Diskin-
Posner, Y.; Avram, L.; Milstein, D. Angew. Chem., Int. Ed. 2017, 56,
14992. (c) Zultanski, S. L.; Zhao, J.; Stahl, S. S. J. Am. Chem. Soc.
2016, 138, 6416. (d) Yamaguchi, K.; Kobayashi, H.; Oishi, T.;
Mizuno, N. Angew. Chem., Int. Ed. 2012, 51, 544. (e) Soule, J. F.;
Miyamura, H.; Kobayashi, S. J. Am. Chem. Soc. 2011, 133, 18550.
(f) Zweifel, T.; Naubron, J.-V.; Grutzmacher, H. Angew. Chem., Int.
̈
Ed. 2009, 48, 559. (g) Nordstrøm, L. U.; Vogt, H.; Madsen, R. J. Am.
Chem. Soc. 2008, 130, 17672. (h) Personick, M. L.; Madix, R. J.;
E
DOI: 10.1021/acs.orglett.8b03542
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Lett. 2015, 56, 3799. (l) Vanjari, R.; Allam, B. K.; Singh, K. N. RSC
Adv. 2013, 3, 1691. (m) Binh Nguyen, T.; Ermolenko, L.; Tran Huu
Dau, M.-E.; Al-Mourabit, A. Heterocycles 2014, 88, 403. (n) Liu, Y.;
Shi, S.; Achtenhagen, M.; Liu, R.; Szostak, M. Org. Lett. 2017, 19,
1614. (o) Vanjari, R.; Allam, B. K.; Singh, K. N. Tetrahedron Lett.
2013, 54, 2553. (p) Lebleu, T.; Kotsuki, H.; Maddaluno, J.; Legros, J.
Tetrahedron Lett. 2014, 55, 362.
(17) Ma, J.; Zhang, F.; Zhang, J.; Gong, H. Eur. J. Org. Chem. 2018,
2018, 4940.
(18) (a) Liu, H.; Zhao, L.; Yuan, Y.; Xu, Z.; Chen, K.; Qiu, S.; Tan,
H. ACS Catal. 2016, 6, 1732. (b) Mali, S. M.; Bhaisare, R. D.; Gopi,
H. N. J. Org. Chem. 2013, 78, 5550. (c) Miraki, M. K.; Yazdani, E.;
Ghandi, L.; Azizi, K.; Heydari, A. Appl. Organomet. Chem. 2017, 31,
No. e3744. (d) Kooti, M.; Nasiri, E. Appl. Organomet. Chem. 2018, 32,
No. e3990.
(19) Um, S.-J.; Kwon, Y.-J.; Han, H.-S.; Park, S.-H.; Park, M.-S.;
Rho, Y.-S.; Sin, H.-S. Chem. Pharm. Bull. 2004, 52, 501.
(20) Wirth, D. D.; Baertschi, S. W.; Johnson, R. A.; Maple, S. R.;
Miller, M. S.; Hallenbeck, D. K.; Gregg, S. M. J. Pharm. Sci. 1998, 87,
31.
(21) Stubba, D.; Lahm, G.; Geffe, M.; Runyon, J. W.; Arduengo, A.
J., III; Opatz, T. Angew. Chem., Int. Ed. 2015, 54, 14187.
F
DOI: 10.1021/acs.orglett.8b03542
Org. Lett. XXXX, XXX, XXX−XXX