Concise total synthesis of antiarrhythmic drug dronedarone via a conjugate addition followed intramolecular heck cyclization

Article abstract of DOI:10.1002/jhet.4316

A concise, scalable, and an efficient total synthesis for dronedarone (2) was described using conjugate addition followed by intramolecular Heck cyclization. The other key reaction includes selective reduction of nitro functionality and addition of lithiated terminal alkyne to the aldehyde. The overall yield of this approach is 44% in six steps.

Full text of DOI:10.1002/jhet.4316

Concise Total Synthesis of Antiarrhythmic Drug Dronedarone via a
Conjugate Addition Followed Intramolecular Heck Cyclization
Sai Reddy Doda 1, Madhu Madasu 1, Prem Kumar Begari 1, Krishna Rao Dasari 1, Gangadhar
Thalari, 2 Sudhakar Kadari 2, 4, * and J. S. Yadav 1, 3,
*
1Department of Organic Synthesis & Process Chemistry, CSIR – Indian Institute of Chemical
Technology, Hyderabad 500007, India; 2Department of Chemistry, Osmania University,
Hyderabad-500 007 India; 3School of Science, Indrashil University, Kadi, Gujarat, India; 4A1
Green pharma solutions, miyapur , Hyderabad-500049.
* Corresponding author Email: contact@greenpharmas.com; yadavpub@gmail.com.
Abstract
A concise, scalable, and an efficient total synthesis for dronedarone (2) was described using
conjugate addition followed by intramolecular Heck cyclization. The other key reaction
includes selective reduction the of nitro functionality and addition of lithiated terminal alkyne
to the aldehyde. The overall yield of this approach is 44% in 6 steps.
Keywords
Total synthesis; dronedarone; antiarrhythmic drug; conjugate addition; intramolecular Heck
cyclization; C-C bond formation
Introduction
Atrial fibrillation (AF) is the most common sustained arrhythmia and is an irregular heartbeat
disease that can lead to heart stroke, blood clots, heart failure, and other major heart-related
complications.[1] In 2016, the Global Burden of Disease project estimated there are at least
46.3 million people suffering with AF worldwide, with a 3-fold increase over the past 50
years.[2] Untreated AF doubles the risk of major heart-related deaths and is associated with a
5-fold increased risk of heart stroke. Amiodarone (1)[3] (Figure 1) is an effective multichannel
blocker and is the drug of choice to treat AF. Amiodarone (1) is a widely used class III anti-
arrhythmic drug that effectively blocks aberrant electrical signals in the heart that cause
irregular heartbeat. amiodarone is an iodine-rich benzofuran derivative, and it contains
approximately 37% iodine by weight. Each 200 mg Amiodarone capsule contains
approximately 75 mg of organic iodine, 8-17 % of which is free iodine: more than 100-times
excess iodine that is required for normal daily function. The regular use of amiodarone causes
several diseases, such as thyroid dysfunction pulmonary fibrosis and liver related disease, and
can accumulate in adipose tissues, liver, muscle, and lung tissue for up to 100 days.[4]
Dronedarone (2) is a modified structural analog with electrophysiologic similarities to
This article has been accepted for publication and undergone full peer review but has
not been through the copyediting, typesetting, pagination and proofreading process
which may lead to differences between this version and the Version of Record. Please
cite this article as doi: 10.1002/jhet.4316
This article is protected by copyright. All rights reserved.

amiodarone (1) and is developed by Sanofi Pharma. Unlike amiodarone, the benzofuranyl
ring of dronedarone (2) is not iodinated, while an additional sulfonamide modification on
benzofuran significantly decreases half-life and lipophilicity, resulting in drastically lowered
tissue accumulation. The minimal side effects of dronedarone as a potent multi-channel
blocker led to U.S. FDA approval in 2009 for atrial fibrillation.
Figure 1: Antiarrhythmic agents’ amiodarone (1) and dronedarone (2)
[5]
The first total synthesis of dronedarone was reported in 1993 by Gubin et al.
Several
synthetic routes for total synthesis of dronedarone have since been reported using diverse
[6]
methods.
As a part of our work on the total synthesis of biologically active natural
products,[7] herein we reported a novel and efficient total synthesis of dronedarone based on a
conjugate addition followed by an intramolecular Heck Coupling reaction strategy.
Results and Discussion
Retrosynthetic Analysis of 2
The retrosynthetic analysis of the dronedarone is outlined in Scheme 1. The target molecule
dronedarone (2) would be generated by late-stage sulfonamide formation and reduction from
3, which could be anticipated from two intermediates 4 and 5 using conjugate addition
followed by intramolecular Heck cross-coupling. The advanced intermediate 5 could be
synthesized from intermediate 6, which was obtained from 4-hydroxybenzaldehyde 7.
2
This article is protected by copyright. All rights reserved.

Scheme 1. Retrosynthetic analysis of dronedarone (2)
Synthesis of 2
As depicted in the Scheme 2, the target molecule was synthesized from 4-hydroxy
benzaldehyde 7, which was treated with commercially available N-butyl-N-(3-
chloropropyl)butan-1-amine (8) and K2CO3 under reflux to access aldehyde 6. The compound
6 was treated with lithiated terminal alkyne 9 to provide racemic alcohol 10 in 87% yield,
which was then oxidized to the ketone by treatment with MnO2 in DCM, providing compound
5 in 94% yield. Having sufficient amounts of key fragments 4 and 5 in hand, the stage was set
for the crucial coupling reaction.[8] The conjugate addition of 2-Iodo-4-nitrophenol 4 to the
o
ynone 5 in the presence of potassium phosphate in acetonitrile at 75 C, followed by
intramolecular Heck reaction provided the benzofuran derivative 3 in 80% over two steps.
The nitro group on benzofuran was selectively reduced to the corresponding amine using zinc
[9]
and ammonium chloride in methanol, providing compound 11 in 91% yield.
Finally,
exclusive mesylation was performed using sodium bicarbonate and methane sulfonyl chloride
in DCM at room temperature for 6 h to provide dronedarone (2) in 92% yield. The analytical
13
and spectral (1H and C NMR) data of synthesized compound 2 are in agreement with the
reported data.[6]
3
This article is protected by copyright. All rights reserved.

Scheme 2. Total Synthesis of dronedarone (2)
Conclusions
In summary, we have achieved the total synthesis of dronedarone (2) in an efficient, eco-
friendly manner using an industrially viable mode starting from commercially available 4-
hydroxy benzaldehyde and economically cheaper reagents. The protocol offers an
operationally simple approach, featuring mild conditions, protecting-group-free synthesis and
superior yield when compared to earlier methods. The highlight of our synthetic strategy is
the conjugate addition of an o-iodophenol derivative followed by intramolecular-Heck
coupling with ynones yielding the desired core in a single step. The present strategy proceeds
in good to excellent yield
Experimental
General details: All reactions are performed under inert atmosphere. The apparatus perfectly
cleaned, and oven dried before the use. All the anhydrous solvents such as acetone, CH3CN,
MeOH, CH2Cl2 and all the other solvents are brought from Fisher Scientific or Sigma Aldrich
and directly used without further purification. The anhydrous THF was distilled over Na and
4
This article is protected by copyright. All rights reserved.

benzophenone. The silica gel (100-200 mesh) for column chromatography was perched from
Merck & Co. The proton and carbon NMR were recorded using 400MHz Bruker Avance II
and 500 MHz Brucker Apex II instrument with TMS as internal solvent. The HRMS spectrum
was recorded using ESI-HRMS instrument. The chemical shifts are in ppm and coupling
constants are reported in hertz (Hz) and the following abbreviations s = singlet, d = doublet, t
= triplet, q = quartet, m = multiplet.
4-(3-(Dibutylamino)propoxy)benzaldehyde (6): K2CO3 (5.37 g, 39.0 mmol) was added to
stirred solution of 4-hydroxybenzaldehyde (1.6 g, 13.65 mmol) and N-butyl-N-(3-
chloropropyl) butan-1-amine (8) (4.0 g, 19.51 mmol) in acetone (80 mL) at room
temperature. The resultant mixture was stirred under reflux for 4h. After completion of the
reaction (The progress of the reaction was monitored by TLC), the rection mixture was
brought to room temperature and the solids were filtered up. The filtrate was evaporated, and
the crude product was purified by silica gel column chromatography (ethyl acetate/ hexane =
1:30) to give compound 6 (4.6 g, 81%). 1H NMR (500 MHz, CDCl3) δ 9.88 (s, 1H), 7.82 (d, J
= 8.9 Hz, 2H), 7.00 (d, J = 8.9 Hz, 2H), 4.11 (t, J = 6.3 Hz, 2H), 2.59 (t, J = 6.9 Hz, 2H),
2.42(t, J = 7.3 Hz, 4H), 1.94 (quint, J = 13.3, 6.6 Hz, 2H), 1.44-1.37 (m, 4H), 1.33-1.24 (m,
4H), 0.88 (t, J = 7.3 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ 190.4, 164.0, 131.6, 129.5,
114.5, 66.3, 53.7, 50.0, 29.0, 26.7, 20.4, 13.8; HRMS (ESI) calcd for C18H30O2N [M + H]+ :
292.2260; found: 292.2271.
1-(4-(3-(Dibutylamino)propoxy)phenyl)hept-2-yn-1-ol (10): n-Butyl lithium was added to a
o
stirred solution of 1-hexyne (9) (1.3 mL, 11.16 mmol) in anhydrous THF (40 mL) at -78 C.
After 20 min, the reaction mixture was allowed to stir at room temperature for 1 h. The
reaction mixture was then cooled -78 oC and aldehyde (6) (2.5 g, 8.59 mmol) was added. The
resulting mixture was slowly brought into room temperature and allowed to stir for additional
1h then quenched with saturated NH4Cl. The mixture was extracted with ethyl acetate (3 x 30
mL) and the combined organic layers were washed with brine solution, then dried over
Na2SO4. The solvent was removed under vacuum and purified by silica gel column
1
chromatography (ethyl acetate/ hexane = 2:30) to give desired alcohol (10) (2.8 g, 87%). H
NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 5.39 (t, J = 1.8
Hz, 1H), 3.99 (t, J = 6.4 Hz, 2H), 2.57 (t, J = 7.0 Hz, 2H), 2.40 (t, J = 7.3 Hz, 4H), 2.27 (dt, J
= 7.0, 2.1 Hz, 2H), 1.89 (quint, J = 6.4 Hz, 2H), 1.57-1.48 (m, 2H), 1.47-1.36 (m, 6H), 1.34-
13
1.23 (m, 4H), 0.94-0.87 (m, 9H); C NMR (125 MHz, CDCl3) δ 158.7, 133.8, 127.8, 114.1,
86.7, 80.4, 66.2, 63.9, 53.6, 50.2, 30.6, 28.7, 26.5, 21.8, 20.6, 18.4, 13.9, 13.4; HRMS (ESI)
calcd for C24H40O2N [M + H]+ 374.3044; found: 374.3053.
5
This article is protected by copyright. All rights reserved.

1-(4-(3-(Dibutylamino)propoxy)phenyl)hept-2-yn-1-one (5): MnO2 (6.3 g, 72.38 mmol was
added to a stirred solution of the alcohol (10) (2.7 g, 7.23 mmol) in DCM (60 mL) at room
temperature. The resulting solution was stirred for 2 h, after completion of the reaction (the
progress of the reaction was monitored by TLC) the reaction mixture was filtered through
celite. The solvent was removed under vacuum and the crude residue was purified by silica
1
gel column chromatography give to desired ketone as a colourless oil (5) (2.5 g, 94%). H
NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.9 Hz, 2H), 6.93 (d, J = 8.9 Hz, 2H), 4.09 (t, J = 6.4
Hz, 2H), 2.58 (t, J = 7.0 Hz, 2H), 2.49 (t, J = 7.1 Hz, 2H), 2.41 (t, J = 7.3 Hz, 4H), 1.92
(quintet, J = 13.3, 6.4 Hz, 2H), 1.70-1.61 (m, 2H), 1.55-1.46 (m, 2H), 1.45-1.35 (m, 4H),
13
1.34- 1.23 (m, 6H), 0.96 (t, J = 7.3 Hz, 3H), 0.89 (t, J = 7.3 Hz, 6H); C NMR (125 MHz,
CDCl3) δ 176.8, 163.8, 131.7, 130.0, 114.0, 95.6, 79.5, 66.4, 53.8, 50.1, 29.8, 29.2, 26.8, 21.9,
20.6, 18.7, 13.9, 13.4; HRMS (ESI) calcd for for C24H38O2N [M + H]+ : 372.2887; found:
372.2897.
(2-Butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (3) :
K3PO3 (572 mg, 2.7 mmol) was added to a stirred solution of o-iodonitrophenol (715 mg, 2.7
mmol) and activated alkyne (5) (1.0 g, 2.7 mmol) in CH3CN (10 mL). The resultant mixture
o
was stirred at 75 C until the reaction reached to completion. After completion, the reaction
mixture was diluted with water (20 mL) and extracted with ethyl acetate (2 x 20 mL). The
combined organic extracts were washed with brine, dried over anhydrous Na2SO4 and the
solvent was removed under vacuum to give crude product. The crude product was used for
next step without further purification. The crude product was (2.7 mmol)), PPh3 (70 mg, 0.27
mmol), Ag2CO3 (740 mg, 2.7 mmol), in CH3CN (15 mL) was stirred at 115 oC for 15 h under
inert atmosphere. After completion (the progress of the reaction was monitored by TLC), the
mixture was brought into room temperature and diluted with water (15 mL) and extracted
with ethyl acetate (3 x 15 mL). The combined organics were dried over anhydrous Na2SO4,
and the solvent was removed under vacuum to give crude product. The crude product was
purified by column chromatography (silica gel, ethyl acetate/hexane = 1:1) to give compound
3 (1.0 g, 80%). 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 2.1 Hz, 1H), 8.22 (dd, J = 9.1, 2.3
Hz, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.56 (d, J = 8.9 Hz, 1H), 6.98 (d, J = 8.8 Hz, 2H), 4.12 (t, J
= 6.2 Hz, 2H), 2.92 (t, J = 7.6 Hz, 2H), 2.60 (t, J = 7.0 Hz, 2H), 2.42 (t, J = 7.2 Hz, 4H), 1.95
(quint, J = 13.1, 6.5 Hz, 2H), 1.76 (quint, J = 15.2, 7.6 Hz, 2H), 1.46- 1.24 (m, 10H), 0.93-
13
0.86 (m, 9H); C NMR (125 MHz, CDCl3) 189.0, 167.0, 163.6, 156.2, 144.5, 131.6, 130.6,
127.9, 120.1, 117.6, 117.3, 114.4, 111.3, 66.6, 53.9, 50.3, 29.9, 29.3, 27.9, 27.0, 22.3, 20.6,
14.0, 13.6; ESI-HRMS m/z calcd. for C30H41O5N2 [M + H]+ : 509.2985; found: 509.3010.
6
This article is protected by copyright. All rights reserved.

(5-amino-2-butylbenzofuran-3-yl)(4-(3(dibutylamino)propoxy)phenyl)methanone (11):
Added saturated ammonium chloride (408 mg, 7.7 mmol) slowly to a stirred solution of
nitroarene 700 mg, 1.37 mmol) and zinc dust (1.37 g, 208 mmol) in MeOH (20 mL). The
resultant mixture was stirred for 30 min. After completion (the progress of the reaction was
monitored by TLC), the reaction mixture was quenched with saturated Na2CO3 (20 mL) and
extracted with CH2Cl2 (3 ×15 mL). The combined organics were dried over anhydrous
Na2SO4, and the solvent was removed under vacuum to give crude product. The crude product
was purified by column chromatography (silica gel, ethyl acetate/hexane = 2:1) to give
compound 11 (600 mg, 91%) as a colourless liquid. 1H NMR (500 MHz, CDCl3) δ 7.82 (d, J
= 8.9 Hz, 2H), 7.23 (d, J = 8.6 Hz, 1H), 6.94 (d, J = 8.9 Hz, 2H), 6.66 (d, J = 2.1 Hz, 1H),
6.62 (dd, J = 8.6, 2.4 Hz, 1H), 4.10 (t, J = 6.4 Hz, 2H), 3.54 (br s, 2H), 2.84 (t, J = 7.6 Hz,
2H), 2.59 (t, J = 6.9 Hz, 2H), 2.42 (t, J = 7.3 Hz, 4H), 1.94 (quint, J = 13.4, 6.6 Hz, 2H), 1.75-
1.28 (m, 2H), 1.45-1.38 (m, 4H), 1.37-1.24 (m, 6H), 0.91-0.85 (m, 9H); 13C NMR (125 MHz,
CDCl3) δ 190.6, 164.9, 162.8, 148.0, 142.5, 131.5, 131.5, 127.9, 116.4, 114.0, 112.9, 111.0,
106.1, 66.4, 53.9, 50.2, 30.0, 29.3, 27.8, 27.0, 22.2, 20.6, 14.0, 13.6; ESI-HRMS m/z calcd.
for C30H43O3N2 [M + H]+ : 479.3240; found: 479.3268.
N-(2-Butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)methanesul
fonamide (2): Sodium bicarbonate (140 mg, 1.67 mmol) was added to a stirred solution of
the compound 11 (500 mg, 1.046 mmol) in dichloromethane (10 mL) and methane sulfonyl
o
chloride (119 mg, 1.046 mmol) was added at 35 C. The resultant solution was stirred under
reflux for 6 h, After completion (the progress of the reaction was monitored by TLC), the
reaction mixture was quenched with water (10 mL). The mixture was extracted with DCM
(20 x 3) and dried over Na2SO4. The solvent was removed under vacuum to give crude product
o
and n-hexane (100 mL) was added to the crude product and stirred at 25 C for overnight to
1
afford the title compound 2 (530 mg, 92%) as colorless oil. H NMR (500 MHz, CDCl3) δ
7.82 (d, J = 8.9 Hz, 2H), 7.46 (d, J = 8.7 Hz, 1H), 7.28-7.23 (m, 2H), 6.94 (d, J = 8.9 Hz, 2H),
4.10 (t, J = 6.4 Hz, 2H), 2.92 (s, 3H), 2.87 (t, J = 7.6 Hz, 2H), 2.59 (t, J = 6.9 Hz, 2H), 2.42 (t,
J = 7.3 Hz, 4H), 1.94 (quint, J = 13.4, 6.6 Hz, 2H), 1.71 (m, 2H), 1.45-1.38 (m, 4H), 1.37-
13
1.24 (m, 6H), 0.91-0.85 (m, 9H); C NMR (75 MHz, CDCl3) δ 190.3, 165.4, 163.1, 151.6,
132.7, 131.6, 131.1, 128.0, 120.1, 116.6, 115.4, 114.1, 111.5, 66.4, 53.7, 50.1, 38.7, 29.9,
29.0, 27.9, 27.7, 22.1, 20.5, 14.0, 13.5; ESI-HRMS m/z calcd. for C31H45O2N2S [M + H]+ :
557.3020; found: 557.3043.
Acknowledgments: S.K thanks the DST-SERB (Young scientist File: CS-138/2012), New
Delhi, India, for financial support.
7
This article is protected by copyright. All rights reserved.

Supplementary Materials: 1H and 13C NMR spectra of unknown compounds.
References
1. Recent Reviews on atrial fibrillation: (a) Amin A.; Houmsse, A.; Ishola, A.; Tyler, J.;
Houmsse, M. Avicenna J Med. 2016, 6, 8–16. (b) Xu, J.; Luc, J. G.; Phan, K. J Thorac Dis
2016, 8, E886–E900. (c) Staerk, L.; Sherer, J. A.; Ko, D.; Benjamin, E. J.; Helm, R. H.
Circulation Research 2017, 120, 1501–1517.
2. (a) Morillo1, C. A.; Banerjee, A.; Perel, P.; Wood, D.; Jouven, X. J. Geriatr Cardiol 2017,
14, 195–203. (b) Kornej, J.; Börschel, C. S.; Benjamin, E. J.; Schnabel, R. B. Circulation
Research 2020, 127, 4–20.
3. Singh, S. N.; Fletcher, R. D.; Fisher, S. G.; Singh, B. N.; Lewis, H. D.; Deedwania, P. C.;
Massie, B. M.; Colling, C.; Layyeri, D. New Eng. J. Med. 1995, 333, 77.
4. Tsadok, M. A.; Jackevicius C. A.; Rahme, E.; Essebag, V.; Eisenberg, M. J.; Humphries,
K. H.; Tu, J. V.; Behlouli, H.; Joo, J.; Pilote. L. CMAJ, 2011, 183, 817-823.
5. Gubin, J.; Chatelaine, P.; Lucchetti, J.; Chastre.; G. Rosseels.; Henri, I. U.S. patent
5223510, 1993.
6. (a) Gutman, A.; Nisnevich, G.; Yudovitch, L. U. S. patent 7,312,345 B2, 2007. (b) Fino,
N.; Leroy, C. U. S. patent 6828448 B2, 2004. (c) Biard, M., U. S. Patent 6,846,936 B2,
2005. (d) Mahender, M.; Saravanan, M.; Sridhar, Ch.; Chandrashekar, E. R. R.; Jaydeep
Kumar, L.; Jayashree, A.; Bandichhor, R. Org. Process Res. Dev. 2014, 18, 157–162; (e)
Mohanarangam, S.; Satyanarayana, B.; Chandrashekar, R. E.; Vijayabhaskar, B.; Reddy, P.
P. J. Chin. Chem. Soc. 2011, 58, 841−845; (f) Okitsu, T.; Ogasahara, M.; Wada, A. Chem.
Pharm. Bull. 2016, 64, 1149–1153; (g) Piotrkowska, B.; Nerdinger, S.; Schreiner, E.; Selic,
L.; Graczyk, P. P. Bioorganic & Medicinal Chemistry 2018, 26, 4330–4335; (h) Santos,
M.; García, L. C.; Checuraa, C.; Donadío, L. G.; Fernandezc, C.; Orgueirac, H.; Cominb M.
J.; Journal of Pharmaceutical and Biomedical Analysis 2015, 114,441–446; (i) Li, F.; Jin,
C.; Zou, J.; Wu. J. Bulletin of the Korean Chemical Society 2014, 35, 1970–197; (j) Raja
Gopal, P.; Chandrashekar, E. R. R.; Saravanan, M.; Vijay Bhaskar, P.; Veera Somaiah, P. J
Chem Sci. 2012, 124, 1077–1085.
7. (a) Mohapatra, D. K.; Das, P. P.; Reddy, D. S.; Yadav, J. S. Tetrahedron Lett. 2009, 50,
5941-5944; (b) Reddy, D. S.; Kutateladze, A. G. Org. Lett. 2016, 18, 4860-4863; (c)
Mohapatra, D. K.; Reddy, D. S.; Ramaiah, M. J.; Ghosh, S.; Pothula, V.; Lunavath, S.;
8
This article is protected by copyright. All rights reserved.

Thomas, S.; Valli. S. N.; Bhadra, M. P.; Yadav, J. S. Bioorg. Med. Chem. Lett. 2014,
24,1389-1396; (d) Mohapatra, D. K.; Reddy, D. S.; Mallampudi, N. A.; Yadav, J. S. Eur. J.
Org. Chem. 2014, 5023-5032; (e) Mohapatra, D. K.; Reddy, D. S.; Mallampudi, N. A.;
Gaddam, J.; Polepalli, S.; Jainb, N.; Yadav, J. S. Org. Biomol. Chem. 2014, 12, 9683-9695;
(f) Reddy, D. S.; Kutateladze, A. G. Org. Lett., 2019, 21, 2855-2858; (g) Reddy, D. S.;
Kutateladze, A. G. Tetrahedron Lett. 2016, 57, 4727; (h) Kutateladze, A. G.; Reddy, D. S.
J. Org. Chem. 2017, 82, 3368; (i) Reddy, D. S.; Mukhina, O. A.; Cronk, W. C.;
Kutateladze, A.G. Pure Appl. Chem. 2017, 89, 259-268.
8. (a) Yin, B.-L.; Cai, C.-B.; Zeng, G.-H.; Zhang, R.-Q.; Li, X.; Jiang, H.-F. Org. Lett. 2012,
14, 1098; (b) Ye, S.-Q.; Liu, G.; Pu, S.-Z.; Wu, J. Org. Lett. 2012, 14, 70 ; (c) Liu, Y.; Ma,
S.-M. Org. Lett. 2012, 14, 720; (d) Schevenels, F.; Marko, I. E. Org. Lett. 2012, 14, 1298;
(e) Li, C.-L.; Zhang, Y.-C.; Li, P.-H.; Wang, L. J. Org. Chem. 2011, 76, 4692; (f) Markina,
N. A.; Chen, Y.; Larock, R. C. Tetrahedron 2013, 69, 2701; (g) O'Connor, M.; Sun, C.;
Guan, X.; Sabbasani, V. R.; Lee, D. Angew. Chem. Int. Ed. 2016, 55, 2222–2225; (h) Ma,
D.-W.; Cai, Q.; Xie, X.-A. Synlett 2005, 1767 ; (i) 48.
Ma, J.; Vannam, R.; Terwilliger,
D.; Peczuh M.W. Tet. Lett. 2014, 55, 4255-4259; (j) Sabbasani, V. R.; Huang, G.; Xia, Y.;
Lee, D. Chem. - Eur. J. 2015, 21, 17210; (k) Sabbasani, V. R.; Lee, D. Org. Lett. 2015, 17,
4878. (l) Sabbasani, V. R.; Lee, H.; Xie, P.; Xia, Y.; Lee, D. Chem. - Eur. J. 2017, 23,
8161 ; (m) Sabbasani, V. R.; Gupta, S.; Yun, S. Y.; Lee, D. Org. Chem. Front. 2018, 5,
1532; (n) Liao, Y.; Smith, J.; Fathi, R.; Yang, Z. Org. Lett. 2005, 7, 2707; (o) Liao, Y.;
Reitman, M.; Zhang, Y.; Fathi, R.; Yang, Z. Org. Lett. 2002, 4, 2607; (p) ) Sabbasani. V.
R.; Lee, H.; Xia, Y.; Lee, D. Angew. Chem. Int. Ed. 2016, 55, 1151–1155.; (q) Vannam, R.;
Lambert, W. D.; Xie, Y.; Wang, H.; Giglio, B.; Ma, X.; Wu, Z.; Fox, J.; Li, Z. Chemical
Communications, 2019, 55, 2485-2488;
9. (a) Orlandi, M.; Brenna, D.; Harms, R.; Jost, S.; Benaglia, M. Org. Process Res. Dev. 2016,
22, 430−445. (b) Kadam, H. K.; Tilve, S. G. RSC Adv. 2015, 5, 83391-83407; (c) Vannam,
R.; Peczuh, M.W. Org. Lett. 2013, 15, 4122-4125; (d) Sabbasani, V. R.; Lee, D. Org. Lett.
2013, 15, 3954–3957.
9
This article is protected by copyright. All rights reserved.