N-(Triisopropylsilyl)pyrrole. A progenitor "par excellence" of 3-substituted pyrroles

Abstract

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 a positions. 1 -(Triisopropylsilyl) pyrrole (1) undergoes highly preferential kinetic electrophilic substitution at the ß position with a variety of electrophiles (Br+, I+, N02+, 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 a positions is decelerated by a factor of >104, vs pyrrole at the same sites, without affecting reactivity at the ß positions. l-(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 /3-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. * Contribution no. 792.

Regioselective aromatic C–H silylation of five-membered heteroarenes with fluorodisilanes catalyzed by iridium(i) complexes

“…GC analyses were performed on a Hitachi G-3500 instrument equipped with a glass column (OV-101 on Uniport B, 2 m). 1,2-Di-tert-butyl-1,1,2,2-tetrafluorodisilane, 1 methyl 3-thiophenecarboxylate, 2 1-triisopropylsilylpyrrole, 3 1-triisopropylsilylindole, 4 [Ir(OMe)(COD)] 2 , 5 2,9-dibutyl-1,10-phenanthroline, 6 2,9-ditert-butyl-1,10-phenanthroline, 6 and 2-tert-butyl-1,10-phenanthroline 7 were synthesized by the reported procedures. 2,9-Diisopropyl-1,10-phenanthroline and 2-isopropyl-1,10-phenanthroline were prepared by the methods similar to those for 2,9-di-sec-butyl-1,10-phenanthroline 8 and 2-sec-butyl-1,10-phenanthroline, 9 respectively.…”

Tandem radical addition/cyclization of 1-(2-iodoethyl)indoles and pyrroles with methyl acrylate under Fenton-type conditions

“…Thus, 1-(2-iodoethyl)-1H-pyrrole-3-carbaldehyde 9 was synthesized by alkylation of 3-formylpyrrole 8 12 followed by halogen exchange (Scheme 5). 8,13 Surprisingly, the main cyclization product was 11, reflecting the attack of the electrophilic radical at position C-2, and no trace of a product resulting from attack at 5-C was detected. …”

“…Aqueous sodium hydroxide (50%, 5 mL) was added at 0 ºC to a stirred solution of pyrrole-3-carbaldehyde (8,13 0.50 g, 5.26 mmol) and tetra(nbutyl)ammonium iodide (1.89 g, 5.26 mmol) in 1,2-dichloroethane (10 mL). The mixture was vigorously stirred and heated at reflux for 1.5 h. The cooled mixture was diluted with water and extracted with dichloromethane.…”

A facile non-oxidative method for synthesizing 1,3-disubstituted pyrroles from pyrrolidine and aldehydes

“…On heating a mixture of 1 and an excess of cyclohexanecarbaldehyde (3) in toluene using a 1,3-bis(cyclohexylmethyl)pyrrole (4) was obtained in 17% yield, accompanied with enamine 5 (Scheme 1). The yield of 4 was improved up to 32% when a mixture of 3 and 5 was refluxed in toluene for 19 h and the addition of a catalytic amount of a Brønsted acid, such as p-toluenesul fonic acid, pyridinium p-toluenesulfonate and sulfuric acid, was ineffective under the conditions.…”