Synthesis of new enantiopure thioureas derived from (S)-proline

Article abstract of DOI:10.1080/10426507.2012.736897

Enantiopure thiourea derivatives, containing pyrrolidine ring, were prepared by the reaction of N-Boc-(S)-2-aminomethylpyrrolidine (6) with thioisocyanates 8.

Full text of DOI:10.1080/10426507.2012.736897

This article was downloaded by: [RMIT University]
On: 06 October 2013, At: 04:23
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
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Synthesis of New Enantiopure Thioureas
Derived from (S)-Proline
a
Aneta Wróblewska a & Grzegorz Mlostoń
a Department of Organic and Applied Chemistry , University of Łódź
, Łódź , Poland
Accepted author version posted online: 31 Oct 2012.
To cite this article: Aneta Wróblewska & Grzegorz Mlostoń (2013) Synthesis of New Enantiopure
Thioureas Derived from (S)-Proline, Phosphorus, Sulfur, and Silicon and the Related Elements, 188:4,
509-511, DOI: 10.1080/10426507.2012.736897
To link to this article: http://dx.doi.org/10.1080/10426507.2012.736897
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

Phosphorus, Sulfur, and Silicon, 188:509–511, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.736897
SYNTHESIS OF NEW ENANTIOPURE THIOUREAS
DERIVED FROM (S)-PROLINE
Aneta Wro´blewska and Grzegorz Mloston´∗
Department of Organic and Applied Chemistry, University of Ło´dz´, Ło´dz´, Poland
GRAPHICAL ABSTRACT
Abstract Enantiopure thiourea derivatives, containing pyrrolidine ring, were prepared by the
reaction of N-Boc-(S)-2-aminomethylpyrrolidine (6) with thioisocyanates 8.
Keywords (S)-proline; (S)-prolinamine; thioureas; organocatalysts; ligands
INTRODUCTION
Thiourea derivatives are widely explored in the area of organocatalysis and asymmet-
ric synthesis. They are known as relatively easily available and effective organocatalysts
for Strecker reaction, Mannich reaction, Michael reaction, and many others.1,2 Especially
attractive are thiourea derivatives containing pyrrolidine ring, because of the presence of
the secondary nitrogen atom and stereogenic center located on the C(2) atom.3–6 Several
papers describing this type of thioureas were published recently.7,8
RESULTS
The goal of the present study was the synthesis of a series of optically active pyrro-
lidine derivatives 10 functionalized with thiourea moiety. The key starting material was
enantiopure, commercially available (S)-proline (1). N-Boc-(S)-2-aminomethylpyrrolidine
(6) was synthesized in fair overall yield based on the known literature protocols.9,10 The
initial step was the protection of the N-atom of pyrrolidine ring. Next, alcohol 3 obtained
after reduction of the carboxylic function, was treated with tosyl chloride yielding tosylate
4. The latter was converted into the azide 5, which upon hydrogenolysis, performed in the
presence of Pd/C, gave the desired amine 6 (Scheme 1). Its spectroscopic data perfectly
fitted with those given in a recent literature report.10
Received 1 October 2012; accepted 2 October 2012.
Address correspondence to Grzegorz Mloston´, Department of Organic and Applied Chemistry, University
of Ło´dz´, Tamka 12, 91-403 Ło´dz´, Poland. E-mail: gmloston@uni.lodz.pl
509

´
´
510
A. WROBLEWSKA AND G. MLOSTON
Scheme 1
On the other hand, a series of thioisocyanates 8 was prepared by the reaction of
thiophosgene with the corresponding primary amines 7 in dichloromethane at 0◦C, in the
presence of sodium bicarbonate using a two-phase system (Scheme 2). The IR spectra reg-
istered for products 8 displayed the presence of a strong absorption band at ca. 2200 cm−1
,
characteristic for the N C S group.
Scheme 2
Thioureas 9a–f were synthesized by the reaction of amine 6 with thioisocyanates
8a–f under mild conditions (Scheme 3). Finally, deprotection of the N-atom by treatment
of 9 with trifluoroacetic acid (TFA) in dichloromethane solution at 0◦C led to the target
products 10, which were purified either by column chromatography or by crystallization.
All products 10 were obtained as crystalline materials in good yields. In the 13C NMR
spectra, characteristic absorption of the C S group appeared in the region 157–160 ppm.

SYNTHESIS OF NEW ENANTIOPURE THIOUREA
511
Scheme 3
CONCLUSIONS
A series of enantiopure thioureas 10a–f containing the N-unprotected pyrrolidine
ring was obtained and characterized by means of spectroscopic methods. All of them are
attractive as organocatalysts and/or ligands. Their exploitation as organocatalysts in diverse
asymmetric reactions is in progress.
REFERENCES
1. Zhang, S.; Wang, W. Proline derivatives. In: Q.-L. Zhou (Ed.), Privileged Chiral Ligands and
Catalysts; Wiley-VCH Verlag: Weinheim, 2011.
2. Wende, R. C.; Schreiner, P. R. Green Chem. 2012, 14, 1821-1849.
3. Cao, X.-Y.; Zheng, J.-Ch.; Li, Y.-X.; Sun, Z.-C.; Sun, X.-L.; Wang, B.-Q. Tetrahedron 2010, 66,
9703-9707.
4. Cao, Ch.-L.; Sun, X.-L.; Zhou, J.-L.; Tang, Y. J. Org. Chem. 2007, 72, 4073-4076.
5. Okino, T.; Hoashi, Y.; Furukawa, T.; Xu, X.; Takemoto, Y. J. Am. Chem. Soc. 2005, 127, 119-125.
6. Vachal, P.; Jacobson, E. N. J. Am. Chem. Soc. 2002, 124, 10012-10014.
7. Kokotos, Ch., G.; Limnios, D.; Triggidou, D.; Trifonidou, M.; Kokotos, G. Org. Biomol. Chem.
2011, 9, 3386-3395.
8. Cao, Ch.-L.; Ye, M.-Ch.; Sun, X.-L.; Tang, Y. Org. Lett. 2006, 8, 2901-2904.
9. Saha, S.; Seth, S.; Moorthy, J. N. Tetrahedron Lett. 2010, 51, 5281-5286.
10. Morris, D. J.; Partridge, A. S.; Manville, C. V.; Racys, D. T.; Woodward, G.; Docherty, G.; Wills,
M. Tetrahedron Lett. 2010, 51, 209-212.