Efficient syntheses of (±)-cherylline and latifine dimethyl ether

Article abstract of DOI:10.1080/00397910903109859

A concise route for the syntheses of (±)-cherylline and latifine dimethyl ether is reported. The key steps involved are Michael addition of veratrole with p-methoxy nitrostyrene (for cherylline), anisole with 2,3-dimethoxy nitrostyrene (for latifine), and reduction of nitro intermediate, followed by Pictet-Spengler cyclization. Copyright

Full text of DOI:10.1080/00397910903109859

This article was downloaded by: [Ams/Girona*barri Lib]
On: 10 November 2014, At: 23:01
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Efficient Syntheses of (±)-Cherylline and
Latifine Dimethyl Ether
A. Sanjeev Kumar a , Samir Ghosh a , R. Soundararajan a & G. N.
Mehta b
a Chemical Research and Development Department , Pfizer Ltd. ,
Mumbai, India
b Chemistry Section, Applied Sciences and Humanities Department ,
Sardar Vallabhbhai National Institute of Technology (SVNIT) , Surat,
India
Published online: 06 May 2010.
To cite this article: A. Sanjeev Kumar , Samir Ghosh , R. Soundararajan & G. N. Mehta (2010)
Efficient Syntheses of (±)-Cherylline and Latifine Dimethyl Ether, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:11, 1588-1594,
DOI: 10.1080/00397910903109859
To link to this article: http://dx.doi.org/10.1080/00397910903109859
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 40: 1588–1594, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903109859
EFFICIENT SYNTHESES OF (ꢀ)-CHERYLLINE AND
LATIFINE DIMETHYL ETHER
A. Sanjeev Kumar,1 Samir Ghosh,1 R. Soundararajan,1
and G. N. Mehta2
1Chemical Research and Development Department, Pfizer Ltd.,
Mumbai, India
2Chemistry Section, Applied Sciences and Humanities Department, Sardar
Vallabhbhai National Institute of Technology (SVNIT), Surat, India
A concise route for the syntheses of (ꢀ)-cherylline and latifine dimethyl ether is reported.
The key steps involved are Michael addition of veratrole with p-methoxy nitrostyrene (for
cherylline), anisole with 2,3-dimethoxy nitrostyrene (for latifine), and reduction of nitro
intermediate, followed by Pictet–Spengler cyclization.
Keywords: Michael reaction; Pictet–Spengler cyclization; reduction; tetrahydroisoquinolines
INTRODUCTION
Cherylline (1) and latifine (2) are the two 4-aryltetrahydroisoquinoline
alkaloids isolated from Amaryllidaceae plants. 4-Aryltetrahydroisoquinolines are
of interest because of their various pharmacological activities.[1] For example,
nomifensine 3 and dichlorofensine[2] 4 exhibit central nervous system activity and
inhibit serotonin and dopamine uptake mechanisms (Fig. 1).
There are several reports of the syntheses of (ꢀ)-cherylline[3–11] and
(ꢀ)-latifine,[12–15] which include some efficient chiral syntheses. Most of the reported
methods for the synthesis of (ꢀ)-cherylline are multistep. We report herein an
alternative efficient synthesis of (ꢀ)-cherylline dimethyl ether. The key steps involved
are Michael addition of veratrole with p-methoxy nitrostyrene, reduction of the nitro
intermediate, and then the Pictet–Spengler cyclization.
RESULTS AND DISCUSSION
Our retrosynthetic analysis of (ꢀ)-cherylline dimethyl ether 5 or latifine
dimethyl ether 6 is depicted in Scheme 1. We anticipated that 5 and 6 could be
constructed from amine 7 and 8 via a Pictet–Spengler ring annulation, which, in
turn, could be obtained by reduction of the corresponding nitro intermediates 9
Received February 18, 2009.
Address correspondence to R. Soundararajan, Chemical Research and Development Department,
Pfizer Ltd., Mumbai, India. E-mail: soundara1959@yahoo.com
1588

(ꢀ)-CHERYLLINE AND LATIFINE DIMETHYL ETHER
1589
Figure 1. Aryl-1,2,3,4-tetrahydroisoquinolines.
and 10. The required nitro intermediates would arise from the Michael addition of
veratrole with p-methoxy nitrostyrene (for cherylline) and anisole with 2,3-
dimethoxy nitrostyrene (for latifine).
For cherylline dimethyl ether, veratrole was subjected to Michael reaction with
p-methoxy nitrostyrene 11 in the presence of trifluoroacetic acid (TFA) to
obtain 1-(1-(3,4-dimethoxyphenyl)-2-nitroethyl)-4-methoxybenzene 9 in 90% yield.
Reduction of nitro group with iron under acidic conditions in tetrahydrofuran
(THF) at room temperature gave 2-(3,4-dimethoxyphenyl)-2-(4-methoxyphenyl)
ethanamine 7 in 74% yield. Reaction with ethyl chloroformate using trimethylamine
at room temperature gave ethyl 2-(3,4-dimethoxyphenyl)-2-(4-methoxyphenyl) ethyl-
carbamate intermediate 12, and immediate reduction by lithium aluminium hydride
gave N-methyl amine 13 in 90% yield. The crude amine 13, after the Pictet–Spengler
reaction, gave (ꢀ)-cherylline dimethyl ether 5 in 60% yield (Scheme 2).
For latifine dimethyl ether, anisole was subjected to Michael reaction
with 2,3-dimethoxy nitrostyrene 15 in presence of TFA to obtain 1-(1-(2,3-
dimethoxyphenyl)-2-nitroethyl)-4-methoxybenzene 10 in 50% yield. Reduction of
the nitro group with iron under acidic conditions in THF gave 2-(2,3-
dimethoxyphenyl)-2-(4-methoxyphenyl)ethanamine 8 in 80% yield. The crude amine
8, after Pictet–Spengler reaction, gave (ꢀ)-latifine dimethyl ether 6 in 60% yield
(Scheme 3). A mixture of 8 with formaldehyde and formic acid for 2 h at reflux
undergoes the Pictet–Spengler reaction and reductive N-methylation reaction in a
single step to provide (ꢀ)-latifine dimethyl ether 6 in 60% yield. The key steps in
latifine synthesis was conversion of 2-(2,3-dimethoxyphenyl)-2-(4-methoxyphenyl)
ethanamine 8 to (ꢀ)-latifine dimethyl ether 6 in a single step using excess equivalents
Scheme 1. 5: R1 ¼ R2 ¼ OMe, R3 ¼ H 6: R2 ¼ R3 ¼ OMe, R1 ¼ H 7: R1 ¼ R2 ¼ OMe, R3 ¼ H 8:
R2 ¼ R3 ¼ OMe, R1 ¼ H 9: R1 ¼ R2 ¼ OMe, R3 ¼ H 10: R2 ¼ R3 ¼ OMe, R1 ¼ H.

1590
A. S. KUMAR ET AL.
Scheme 2. (a) Veratrole, TFA, reflux, 3.0 h, 90.0%; (b) Fe, acetic acid, THF, 70 ꢁC, 3.0 h, 74%; (c) ethyl
chloro formate, TEA, THF, 0–5 ꢁC; (d) LAH, THF, reflux, 4.0 h, 90%; and (e) HCHO, acetic acid,
90 ꢁC, 2.0 h, 60%.
Scheme 3. (a) Nitromethane, CH3COONH4, acetic acid, 100 ꢁC, 4.0 h, 60%; (b) anisole, TFA, reflux, 3.0 h,
50%; (c) Fe, acetic acid, THF, 70 ꢁC, 3.0 h, 80%; and (d) HCHO, HCOOH, 90 ꢁC, 2.0 h, 60%.

(ꢀ)-CHERYLLINE AND LATIFINE DIMETHYL ETHER
1591
of aqueous formaldehyde and formic acid. The initial reaction undergoes
Pictet–Spengler cyclization to produce 5,6-dimethoxy-4-(4-methoxyphenyl)-1,2,3,4-
tetrahydro isoquinoline 16 (without isolation) and then reductive N-methylation
reaction in a single step to produce the desired product in good yield.
In short, we have devised a short and efficient method for the syntheses of
(ꢀ)-cherylline and latifine dimethyl ethers. This simple and facile nature of tetrahy-
droisoquinoline synthesis should allow the construction of a wide variety of interest-
ing and useful analogous molecules.
EXPERIMENTAL
Materials and Instruments
All solvents and reagents were purchased from the suppliers and used without
further purification. All nonaqueous reactions were performed in dry glassware
under an atmosphere of dry nitrogen. Organic solutions were concentrated under
reduced pressure. Thin-layer chromatography (TLC) was performed on Merck pre-
coated silica-gel 60F254 plates. 1H and 13C NMR spectra were recorded in dimethyl-
sulfoxide (DMSO-d6) and CDCl3 on a Varian Gemini 400-MHz Fourier transform
(FT) NMR spectrometer. The chemical shifts are reported in d ppm relative to tetra-
methylsilane (TMS). The infrared (IR) spectra were recorded in the solid state as
KBr dispersion using a Perkin Elmer FT-IR spectrophotometer. The mass spectra
were recorded on a Shimadzu liquid chromatography–mass spectrometer (LCMS)
QP 800 and AB-4000 Q-trap LC-MS=MS instruments. Melting points were obtained
by using the open capillary method and are uncorrected.
1-(1-(3,4-Dimethoxyphenyl)-2-nitroethyl)-4-methoxybenzene (9)
A solution of p-methoxy nitrostyrene 11 (6.0 g, 0.033 mol) and veratrole (9.2 g,
0.067 mol) in TFA (30 mL) was refluxed for 3 h. TFA was distilled under pressure,
and saturated NaHCO3 (50 mL) was added. It was extracted with ethyl acetate
(3 ꢂ 30 ml), and combined extracts were dried over sodium sulfate and concentrated.
The residue was purified by column chromatography on silica gel (7:3 hexane and
1
ethyl acetate) to yield 9 as a residue (9.6 g, 90%); IR (KBr, cmꢃ1): 1550 (NO2); H
NMR (DMSO-d6) (d ppm): 3.62 (3H, s, ꢃOCH3), 3.64 (3H, s, ꢃOCH3), 3.66 (3H,
s, ꢃOCH3), 4.63 (1H, t, J ¼ 8.8 Hz, Ar-CH-Ar), 5.21 (2H, d, J ¼ 8.8 Hz, CH2-
NO2), 6.77–7.27 (7H, m, ArH); 13C NMR (DMSO-d6) (d ppm); 47.8 (ArCHAr),
55.4 (OCH3), 55.8 (OCH3), 55.9 (OCH3), 79.1 (CH2-NO2), 111.9 (CHar), 112.2
(CHar), 114.3 (2 ꢂ CHar), 119.8 (Car), 129.0 (2 ꢂ CHar), 132.8 (Car), 133.3 (Car),
148.1 (OCar), 149.1 (OCar), 158.5 (OCar); MS (m=z): 318 [Mþ þ 1].
The 2,3-dimethoxy congener (10) was obtained in the same way as an oil (50%);
IR (KBr, cmꢃ1): 1550 (NO2); HRMS m=z calculated for C17H19NO5 318.1263-
1
[M þ 1], found 318.1260; H NMR (400 MHz, DMSO-d6) (d ppm): 3.72 (3H, s,
ꢃOCH3), 3.74 (3H, s, ꢃOCH3), 3.86 (3H, s, ꢃOCH3), 4.65 (1H, t, J ¼ 8.8 Hz,
Ar-CH-Ar), 5.19 (2H, d, J ¼ 8.8 Hz, CH2-NO2), 6.78–6.98 (5H, m, ArH), 7.21
(2H, d, J ¼ 8.0 Hz, ArH); 13C NMR (400 MHz, DMSO-d6) (d ppm); 46.8 (ArCHAr),
55.4 (OCH3), 55.8 (OCH3), 60.5 (OCH3), 79.2 (CH2-NO2), 111.6 (CHar), 114.4

1592
A. S. KUMAR ET AL.
(2 ꢂ CHar), 120.3 (CHar), 121.9 (CHar), 129.1 (2 ꢂ CHar), 131.9 (Car), 132.7 (Car),
147.8 (OCar), 152.4 (OCar), 157.2 (OCar).
2-(3,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)ethanamine (7)
Iron (10.5 g, 0.189 mol) was added to a solution of 1-(1-(3,4-dimethoxy
phenyl)-2-nitroethyl)-4-methoxybenzene 9 (6.0 g, 0.018 mol) in THF (60 mL) and
acetic acid (60 mL). The reaction mixture stirred at reflux for 3 h. After cooling to
room temperature, the reaction mixture was filtered through a celite bed and basified
with 50% sodium hydroxide solution. This basified solution was extracted ethyl acet-
ate (3 ꢂ 25 mL), dried, filtered, and concentrated to obtain 5.3 g of crude product.
Purification of crude product by column chromatography using 10% methanol in
dichloromethane as an eluent gave 7 (4.0 g, 74%), as a residue; IR (KBr, cmꢃ1):
1
3320 (NH2); H NMR (DMSO-d6) (d ppm): 3.03 (2H, d, J ¼ 7.8 Hz, ꢃCHꢃCH2ꢃ),
3.62 (3H, s, ꢃOCH3), 3.63 (3H, s, ꢃOCH3), 3.65 (3H, s, ꢃOCH3), 3.73 (1H, t,
J ¼ 7.8 Hz, CHꢃCH2), 6.68–7.11 (7H, m, ArH); 13C NMR (DMSO-d6) (d ppm);
47.2 (ArCHAr), 53.7 (CH2ꢃNH2), 55.3 (OCH3), 55.8 (OCH3), 55.9 (OCH3), 112.2
(CHar), 112.3 (CHar), 114.1 (2 ꢂ CHar), 119.9 (Car), 129.1 (2 ꢂ CHar), 136.3 (Car),
136.8 (Car), 147.5 (OCar), 149.0 (OCar), 157.9 (OCar); MS (m=z): 288 [Mþ þ 1].
The 2,3-dimethoxy congener (8) was obtained in the same way as an oil in 80%;
IR (KBr, cmꢃ1): 3320 (NH2); HRMS m=z calculated for C17H21NO3 288.1521
1
[M þ 1], found 288.1522; H NMR (400 MHz, DMSO-d6) (d ppm): 3.03 (2H, d,
J ¼ 7.8 Hz, ꢃCH2ꢃNH2), 3.54 (3H, s, ꢃOCH3), 3.66 (3H, s, ꢃOCH3), 3.72 (3H, s,
ꢃOCH3), 4.21 (1H, t, J ¼ 7.8 Hz, CHꢃCH2), 6.78–6.98 (5H, m, ArH), 7.13 (2H, d,
J ¼ 8.0 Hz ArH); 13C NMR (400 MHz, DMSO-d6) (d ppm); 47.2 (ArCHAr), 46.8
(CH2ꢃNH2), 55.3 (OCH3), 55.9 (OCH3), 60.4 (OCH3), 111.0 (CHar), 114.0
(2 ꢂ CHar), 119.6 (CHar), 124.2 (CHar), 129.4 (2 ꢂ CHar), 135.9 (Car), 137.5 (Car),
147.0 (OCar), 152.9 (OCar), 157.9 (OCar).
2-(3,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)-N-
methylethanamine (13)
Ethyl chloroformate (1.5 g, 0.013 mol) was added to a solution of 2-(3,4-
dimethoxyphenyl)-2-(4-methoxyphenyl)ethanamine 7 (3.5 g, 0.012mol) in THF
(35 mL) and triethyl amine (1.85g, 0.018 mol) at 0–5 ꢁC. The reaction mixture stirred
at 25–35 ꢁC for 1 h. Reaction progress was monitored by TLC and shown to be pure;
it proceeded as such for reduction purposes. Intermediate 12 (ethyl 2-(3,4-
dimethoxyphenyl)-2-(4-methoxyphenyl)ethylcarbamate) was slowly added to the sus-
pension of lithium aluminium hydride (LAH) (2.3 g, 0.06mol) in THF (15 mL) under
an inert atmosphere. After refluxing for 4 h, the reaction mixture was cooled to 5ꢁC,
and chilled water was slowly added to it. The aluminium hydroxide formed was filtered
over celite and washed with chloroform. The filtrate also was extracted with chloroform
(3ꢂ 20mL). All the organic extracts and washings were combined, dried over sodium
sulfate, filtered, and concentrated to obtain 13 as a brown residue 3.3 g (90.0%); IR
(KBr, cmꢃ1): 3120 (NH); HRMS m=z calculated for C18H23NO3 302.3801 [Mþ 1],
found 302.37; 1H NMR (CDCl3) (d ppm): 2.44 (3H, s, NCH3), 3.12 (2H, d, J ¼ 8.0 Hz,
HCHꢃNꢃCH3), 3.78 (3H, s, OCH3), 3.83 (3H, s, OCH3), 3.84 (3H, s, OCH3), 4.08 (1H,

(ꢀ)-CHERYLLINE AND LATIFINE DIMETHYL ETHER
1593
t, J ¼ 7.6 Hz, Ar-CH-Ar), 6.74–7.26 (7H, m, ArH); 13C NMR (CDCl3) (d ppm); 43.9
(NCH3), 49.4 (ArCHAr), 55.3 (OCH3), 55.81 (OCH3), 55.86 (OCH3), 56.6 (NCH2Ar),
112.1 (CHar), 112.2 (CHar), 114.1 (2ꢂ CHar), 119.8 (Car), 129.0 (2ꢂ CHar),
136.2 (Car), 136.8 (Car), 147.5 (OCar), 148.9 (OCar), 157.9 (OCar).
(ꢀ)-Cherylline Dimethyl Ether (5)
A mixture of 13 (2.0 g, 0.006 mol), formaldehyde (0.64 g, 0.007 mol), and acetic
acid (5 mL) was stirred at 90 ꢁC under an inert atmosphere for 2.0 h. After cooling to
room temperature, the reaction mixture was basified with saturated NaHCO3 sol-
ution. This basified solution was extracted ethyl acetate (3 ꢂ 25 mL), dried, filtered,
and concentrated to obtain 1.1 g of crude product. Purification of crude product by
column chromatography using 1% methanol in dichloromethane as an eluent gave 5
(0.93 g, 45%), as a white solid, mp 90–92 ꢁC (lit.[11] mp 90–92 ꢁC); IR (KBr, cmꢃ1):
1610, 1514; HRMS m=z calculated for C19H23NO3 314.1756 [M þ 1], found
314.175; 1H NMR (CDCl3) (d ppm): 2.41 (3H, s, NCH3), 2.44 (1H, m,
CHꢃHCHꢃN), 2.98 (1H, m, CHꢃHCHꢃN), 3.56 (2H, s (br), ArꢃCH2ꢃN), 3.65
(3H, s, OCH3), 3.80 (3H, s, OCH3), 3.86 (3H, s, OCH3), 4.12 (1H, t, ArꢃCHꢃAr),
6.34 (1H, s, 5-CH), 6.56 (1H, s, 8-CH), 6.84 (2H, d, J ¼ 8.8 Hz, 20-CH), 7.11 (2H, d,
J ¼ 8.8 Hz, 30-CH); 13C NMR (CDCl3) (d ppm); 43.9 (NCH3), 45.9 (ArCHAr), 55.3
(OCH3), 55.81 (OCH3), 55.86 (OCH3), 57.7 (NCH2ꢃ), 61.6 (NCH2Ar), 109.7
(CHar), 112.5 (CHar), 113.9 (2 ꢂ CHar), 127.7 (Car), 129.2 (Car), 130.0 (2 ꢂ CHar),
137.7 (Car), 147.5 (OCar), 147.6 (OCar), 158.0 (OCar).
(ꢀ)-Latifine Dimethyl Ether (6)
A mixture of 8 (2.0 g, 0.006 mol), formaldehyde 37% solution in water (2.81 g,
0.034 mol), and formic acid (6 mL) was stirred at 95 ꢁC under an inert atmosphere for
18.0 h. After cooling to room temperature, the reaction mixture was basified with
50% sodium hydroxide solution. This basified solution was extracted ethyl acetate
(3 ꢂ 25 mL), dried, filtered, and concentrated to obtain 0.9 g of crude product.
Purification of crude product by column chromatography using 1% methanol in
dichloromethane as an eluent gave 6 (1.30 g, 60%) as a white solid, mp 86–88 ꢁC
(lit.[16] mp 86–88 ꢁC); IR (KBr, cmꢃ1): 1620, 1520; HRMS m=z calculated for
C19H23NO3 314.1756 [M þ 1], found 314.1758; 1H NMR (400 MHz, CDCl3) (d
ppm): 2.32 (3H, s, NCH3), 2.70 (2H, d, J ¼ 4.4 Hz, CHꢃCH2ꢃN), 3.20 (3H, s,
OCH3), 3.75 (3H, s, OCH3), 3.79 (3H, s, OCH3), 3.34 and 3.80 (each 1H, d,
J ¼ 14.4 Hz, Ar-HCHꢃN), 4.26 (1H, t, J ¼ 4.4 Hz, ArꢃCHꢃAr), 6.76–6.80 (4H,
m, ArH), 7.11 (2H, d, J ¼ 8.8 Hz, ArH); 13C NMR (400 MHz, CDCl3) (d ppm);
40.5 (ArCHAr), 46.1 (NCH3), 55.1 (OCH3), 55.7 (OCH3), 57.9 (NCH2Ar), 59.4
(NCH2), 61.5 (OCH3), 111.1 (CHar), 113.1 (2 ꢂ CHar), 121.1 (CHar), 128.7 (Car),
129.3 (2 ꢂ CHar), 130.2 (Car), 139.9 (Car), 147.8 (OCar), 151.1 (OCar), 157.6 (OCar).
ACKNOWLEDGMENTS
We are grateful to SVNIT, Surat, and the Indian Institute of Chemical
Technology, Hyderabad, for supporting this work.

1594
A. S. KUMAR ET AL.
REFERENCES
1. Zara-Kaczaim, E.; Gyo¨rgy, L.; Deak, G.; Seregi, A.; Doda, M. Synthesis and pharmaco-
logical evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine
uptake and=or possessing a dopaminomimetic property. J. Med. Chem. 1986, 29,
1189–1195.
2. Cherpillod, C.; Omer, L. M. Pharmacological evaluation of some new tetrahydroisoqui-
noline derivatives. J. Clin. Pharmacol. 1982, 20, 324.
3. Brossi, A.; Teitel, S. Total synthesis of racemic cherylline. Tetrahedron Lett. 1970,
417–419.
4. Schwartz, M. A.; Scott, S. W. Biogenetically patterned synthesis of (ꢀ)-cherylline. J. Org.
Chem. 1971, 36, 1827–1829.
5. Kametani, T.; Takahashi, K.; Van Loc, C. Total synthesis of racemic cherylline and
corgoine through quinonoid intermediates. Tetrahedron 1975, 31, 235–238.
6. Hart, D. J.; Cain, P. A.; Evans, D. A. Approaches to the synthesis of masked p-quinone
methides: Applications to the total synthesis of (þ)-cherylline. J. Am. Chem. Soc. 1978,
100, 1548–1557.
7. Irie, H.; Shiina, A.; Fushimi, T.; Katakawa, J.; Fujii, N.; Yajima, H. New synthesis of
isoquinoline alkaloids, thalifoline, corypalline and cherylline. Chem. Lett. 1980, 875–878.
8. Kessar, S. V.; Singh, P.; Chawla, R.; Kumar, P. Cyclization of ortho-halogenated N-
acylbenzylamines: A formal synthesis of racemic cherylline. J. Chem. Soc., Chem. Com-
mun. 1981, 1074–1075.
9. Kametani, T.; Higashiyama, K.; Honda, T.; Otomasu, H. A facile total synthesis of
cherylline via an aziridinium intermediate. J. Chem. Soc., Perkin Trans. 1 1982, 2935.
10. Couture, A.; Deniau, E.; Lebrun, S.; Grandclaudon, P. Asymmetric synthesis of (þ)- and
(–)-latifine. Tetrahedron: Asymmetry 2003, 14, 1309.
11. Reshma, K.; Suvidaha, K.; Santosh, T.; Janardan, K. Alternative synthesis of racemic
cherylline dimethyl ether. Arkivoc 2008, 12, 256–261.
12. Takano, S.; Akiyama, M.; Ogasawara, K. Total synthesis of racemic latifine. Chem. Lett.
1985, 505–506.
13. Gore, V. G.; Narashimhan, N. S. An efficient synthesis of racemic latifine dimethyl ether.
J. Chem. Soc., Perkin Trans. 1 1988, 481.
14. Couture, A.; Deniau, E.; Lebrun, S.; Grandclaudon, P. Total syntheses of (ꢀ)-cherylline
and (ꢀ)-latifine. J. Chem. Soc., Perkin Trans. 1 1999, 789.
15. Honda, T.; Namiki, H.; Satoh, F. Palladium-catalyzed intermolecular lactam formation
of aryl halides and amide-enolates: Syntheses of cherylline and latifine. Org. Lett. 2001,
3, 631–633.
16. Gore, V. G.; Narashimhan, N. S. An efficient synthesis of latifine dimethyl ether. J. Chem.
Soc., Perkin Trans. 1 1988, 481–483.