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Synlett 2009(10): 1680-1684  
DOI: 10.1055/s-0029-1217344
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© Georg Thieme Verlag Stuttgart ˙ New York

Bifunctional Asymmetric Catalysis with Hydrogen Chloride: Enantioselective Ring Opening of Aziridines Catalyzed by a Phosphinothiourea

Tsuyoshi Mita, Eric N. Jacobsen*
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
Fax: +1(617)4961880; e-Mail: jacobsen@chemistry.harvard.edu;
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Publication History

Received 28 February 2009
Publication Date:
02 June 2009 (online)

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Abstract

Ring opening of aziridines with hydrogen chloride to form β-chloroamine derivatives is catalyzed by a chiral phosphinothiourea derivative in high yields and with high enantioselectivities. On the basis of ³¹P NMR studies, activation of HCl appears to proceed via quantitative protonation of the catalyst to afford a phosphonium chloride complex.

Key words

asymmetric catalysis - halogenation - ring opening - carbocations - aziridines

5

HCl: pK a = 1.8 in DMSO and -8.0 in H2O.

8

For example, catalyst 1g can be used effectively in reactions catalyzed by triflic acid (pK a = 0.3 in DMSO and -14 in H2O, respectively). Woll, M. G.; Xu, H.; Tao, Y.; Zuend,
S. J.; Jacobsen, E. N. unpublished results.

15

Ring openings of cyclooctene oxide and cis-stilbene oxide with HCl in the presence of phosphinothiourea 1f proceeded to afford the corresponding trans-chlorohydrins in only 22% ee and 34% ee, respectively.

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Aziridines having different protecting groups such as benzyl, tosyl, benzylcarbamoyl, and also unprotected aziridines gave almost racemic compounds.

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Diastereomeric phosphinothiourea of 1f previously effective for [3+2] cyclization¹¹a was not promising for this reaction (12% ee).

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Zuend, S. J; Coughlin, M. P; Lalonde, M. P.; Jacobsen, E. N. manuscript in preparation.

20

N-Boc-α-cyclohexcylmethyl glycine was fine solid so that optically active crystal could be easily obtained after the recrystallization from the reaction crude (ca. 90% ee) which was prepared through the enantioselective Strecker reaction and hydrolysis followed by Boc protection. Other Boc-protected amino acids are amorphous which need the crystallization after the salt formation with tert-butylamine.

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Kinetic studies of the uncatalyzed hydrochlorination of 2b and 2c using in situ IR spectrometry (Et2O at -40 ˚C) revealed a 1.5-order dependence on [HCl].