An Efficient Synthesis of 2-Diazo-2-(trimethylsilyl)ethanols and Their Application to Pyrazole Synthesis

Abstract

Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate.

Key words

diazoalcohol - 2-diazo-2-(trimethylsilyl)ethanols - di­azo(trimethylsilyl)methylmagnesium bromide - pyrazoles - trimethylsilyldiazomethane

References

• 1 Kanemasa S. Araki T. Kanai T. Wada E. Tetrahedron Lett.  1999,  40:  5059 
• 2 Bolm C. Kasyan A. Drauz K. Günther K. Raabe G. Angew. Chem. Int. Ed.  2000,  39:  2288 
• 3 Alt M. Maas G. Tetrahedron  1994,  50:  7435 
• 4a Bolm C. Kasyan A. Heider P. Saladin S. Drauz K. Günther K. Wanger C. Org. Lett.  2002,  4:  2265 
• 4b Bolm C. Saladin S. Kasyan A. Org. Lett.  2002,  4:  4631 
• 4c Braddock DC. Badine DM. Gottschalk T. Matsuno A. Rodriguez-Lens M. Synlett  2003,  345 
• 4d Ioannou M. Porter MJ. Saez F. Tetrahedron  2005,  61:  43 
• Reactions using trimethylsilyldiazoketones:
• 5a Aoyama T. Shioiri T. Tetrahedron Lett.  1980,  21:  4461 
• 5b Aoyama T. Shioiri T. Chem. Pharm. Bull.  1981,  29:  3249 
• 5c Iso Y. Shindo H. Hamana H. Tetrahedron  2000,  56:  5353 
• 5d Sawada Y. Oku A. J. Org. Chem.  2004,  69:  2899 
• 5e Qiao JX. Cheng X. Modi DP. Rossi KA. Luettgen JM. Knabb RM. Jadhav PK. Wexler RR. Bioorg. Med. Chem. Lett.  2005,  15:  29 
• For reviews on reactions using TMSCHN₂, see:
• 6a Shioiri T. Aoyama T. Science of Synthesis   Vol. 4:  Fleming I. Thieme Verlag; Stuttgart: 2002.  p.569-577  
• 6b Shioiri T. Aoyama T. Advances in the Use of Synthons in Organic Chemistry   Vol. 1:  Dondoni A. JAI Press Ltd.; London: 1993.  p.51-101  
• Reactions using 1-diazo-1-trimethylsilylalkanes except for TMSCHN₂:
• 7a Aoyama T. Shioiri T. Tetrahedron Lett.  1986,  27:  2005 
• 7b Aoyama T. Shioiri T. Tetrahedron Lett.  1988,  29:  6295 
• 7c Aoyama T. Shioiri T. Chem. Pharm. Bull.  1989,  37:  2261 
• 7d Han S. Kass SR. J. Chem. Soc., Perkin Trans. 1  1999,  1553 
• 8 Schöllkopf U. Scholz H.-U. Synthesis  1976,  271 
• 9 Hari Y. Tsuchida S. Aoyama T. Tetrahedron Lett.  2006,  47:  1977 
• 10 For a review: Elguero J. Comprehensive Heterocyclic Chemistry II   Vol. 3:  Shinkai I. Elsevier; Oxford: 1996.  p.1-75  
• 13 Chan KS. Wulff WD. J. Am. Chem. Soc.  1986,  108:  5229 

11

When, during the workup of 2a, the organic extracts were not washed with aq sat. NaHCO₃, no final product 3a was obtained after the reaction with DMAD.

12

The position of the ethoxycarbonyl group in 4 was determined by NOE measurement (Figure [1] ). For example:

Figure 1 NOE data for 4