237404-71-6Relevant academic research and scientific papers
Regioselective introduction of electrophiles in the 4-position of 1- hydroxypyrazole via bromine-lithium exchange
Balle, Thomas,Vedso, Per,Begtrup, Mikael
, p. 5366 - 5370 (2007/10/03)
Two protocols for introduction of electrophiles at the 4-position of 1- hydroxypyrazoles have been developed. The first is deprotonation of 4-bromo- 1-[(tert-butyldiphenylsilyl)oxy]pyrazole (6) with LDA to produce the 5-lithio derivative in which the silyl group migrates spontaneously from oxygen to C-5 affording 4-bromo-5-(tert-butyldiphenylsilyl)-1-lithoxypyrazole (8). Subsequent treatment with t-BuLi causes bromine-lithium exchange to give 5- tert-butyldiphenylsilyl-4-lithio-1-lithoxypyrazole which is trapped with electrophiles affording 4-substituted 5-(tert-butyldiphenylsilyl)-1- hydroxypyrazoles 9a-e in a one-pot sequence. The second is treatment of 4- bromo-1-hydroxypyrazole (5) with excess LDA and trimethylsilyl chloride to produce 3,5-bis(trimethylsilyl)-4-bromo-1-hydroxypyrazole (12), which upon sequential metalation with n-BuLi and reaction with electrophiles affords 4- substituted 3,5-bis(trimethylsilyl)-1-hydroxypyrazoles 13a-e. The tert- butyldiphenylsilyl group of 9a and the trimethylsilyl groups of 12 can be removed selectively by treatment with tetrabutylammonium fluoride in THF in the presence of trifluoroacetic acid.
