93362-53-9Relevant academic research and scientific papers
3-Lithiopyrroles by Halogen-Metal Interchange of 3-Bromo-1-(triisopropylsilyl)pyrroles. Synthesis of Verrucarin E and Other 3-Substituted Pyrroles.
Muchowski, Joseph M.,Naef, Reto
, p. 1168 - 1172 (1984)
3-Lithio-1-(trimethylsilyl)pyrrole (7, Scheme 2), obtained by halogen-metal interchange from the 3-bromo compound 2, reacted with various electrophilic reagents to provide products, which on fluoride ion desilylation, gave 3-substituted pyrroles in good overall yields.One such pyrrole 13 (Scheme 3), was converted into 2-formyl-3-octadecylpyrrole (14), reputed to be a metabolite of the marine sponge Oscarella lobularis. 3,4-Dibromo-1-(triisopropylsilyl)pyrrole (5) was efficiently transformed, by a process involving two conscutive bromine-lithium exchange reactions (Scheme 4), into the antibiotic verrucarin E 17.
N-(Triisopropylsilyl)pyrrole. A Progenitor "Par Excellence" of 3-Substituted Pyrroles
Bray, Brian L.,Mathies, Peter H.,Naef, Reto,Solas, Dennis R.,Tidwell, Thomas T.,et al.
, p. 6317 - 6328 (2007/10/02)
A very effective strategy has been devised for the synthesis of 3-substituted pyrroles based on the use of the triisopropylsilyl (TIPS) moiety as a sterically demanding nitrogen substituent to obstruct the attack of electrophilic reagents at the α positions. 1-(Triisopropylsilyl)pyrrole (1) undergoes highly preferential kinetic electrophilic substitution at the β position with a variety of electrophiles (Br+, I+, NO2+, RCO+, etc.) and fluoride ion induced desilylation of the products provides the corresponding 3-substituted pyrroles in good overall yields.Competitive trifluoroacetylation experiments demonstrate that substitution of TIPS-pyrrole at the α positions is decelerated by a factor of >104, vs pyrrole at the same sites, without affecting reactivity at the β positions. 1-(Triisopropylsilyl)-3-bromopyrrole (2) is readily converted into the 3-lithio compound 44 by bromine-lithium interchange with alkyllithium reagents.This previously unavailable, formal equivalent of 3-lithiopyrrole is itself an excellent source of a wide range of β-substituted pyrroles, many of which would not be directly preparable from 1.TIPS-pyrrole can be 3,4-dihalogenated and these compounds undergo sequential halogen-metal interchange trapping reactions.This process is exemplified by an efficient, three-step synthesis of the antibiotic verrucarin E (63) from the dibromo compound (5).
