An Enantiospecific Approach to Triazolylalanine Derivatives

Abstract

An efficient and practical route to an enantiomerically pure aziridinylmethyl azide is described that can be transformed to the corresponding triazole by a copper-catalysed [3+2] alkyne cycloaddition reaction. The transformation of these intermediates into triazolylalanine-type derivatives by aziridine ring-opening reactions is also described.

Key words

copper catalyst - 1,2,3-triazole - aziridine - cycloaddition - ring-opening reaction - alanine

References and Notes

• For reviews on aziridine chemistry, see:
• 1a McCoull W. Davis FA. Synthesis  2000,  1347 
• 1b Sweeney JB. Chem. Soc. Rev.  2002,  31:  247 
• 1c Hu XE. Tetrahedron  2004,  60:  2701 
• 2 Jamookeeah CE. Beadle CD. Jackson RFW. Harrity JPA. J. Org. Chem.  2008,  73:  1128 
• 3 Fan W.-Q. Katritzky AR. In Comprehensive Heterocyclic Chemistry II   Vol. 4:  Katritzky AR. Rees CW. Scriven EFV. Pergamon Press; Oxford: 1996.  p.1-126  
• 4a For a recent report and lead references see: Kuijpers BHM. Groothuys S. Hawner C. ten Dam J. Quaedflieg PJLM. Schoemaker HE. van Delft FL. Rutjes FPJT. Org. Process Res. Dev.  2008,  12:  503 
• 4b For an excellent overview, see: Dondoni A. Chem. Asian J.  2007,  2:  700 
• 5 The aziridine synthesis is based on studies by Baldwin and co-workers: Baldwin JE. Spivey AC. Schofield CJ. Sweeney JB. Tetrahedron  1993,  49:  6309 
• 6a Huisgen R. Angew. Chem., Int. Ed. Engl.  1963,  2:  565 
• 6b Huisgen R. Angew. Chem., Int. Ed. Engl.  1963,  2:  633 
• 7a Kolb HC. Finn MG. Sharpless KB. Angew. Chem. Int. Ed.  2001,  40:  2004 
• 7b Bock VD. Hiemstra H. van Maarseveen JH. Eur. J. Org. Chem.  2006,  51 
• 8a Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed.  2002,  41:  2596 
• 8b Tornoe CW. Christensen C. Meldal M. J. Org. Chem.  2002,  67:  3057 
• 8c Zhang L. Chen X. Xue P. Sun HHY. Williams ID. Sharpless KB. Fokin VV. Jia G. J. Am. Chem. Soc.  2005,  127:  15998 
• 8d Majireck MM. Weinreb SM. J. Org. Chem.  2006,  71:  8680 
• 8e Boren BB. Narayan S. Rasmussen LK. Zhang L. Zhao H. Lin Z. Jia G. Fokin VV. J. Am. Chem. Soc.  2008,  130:  8923 
• 8f For a recent comprehensive review, see: Meldal M. Tornøe CW. Chem. Rev.  2008,  108:  2952 
• 9 Vedejs E. Klapars A. Warner DL. Weiss AH. J. Org. Chem.  2001,  66:  7542 

10

Whilst the product ee values were not determined, we have previously shown that nucleophilic additions to 3 and subsequent manipulations preserve stereochemical integrity and hence assume that these processes are enantiospecific.