Pyrrole trimethylsilylation

The Teoc group is introduced onto pyrroles or indoles with 4-nitrophenyl 2-(trimethylsilyl)ethyl carbonate and NaH in 61-64% yield. It can be removed with Bu4N F in CH3CN. ... 

The related planar pyrrole analog 118 has also been prepared (2) from either ethyl or benzyl pyrrole-2-carboxylate 116. Direct alkylation with diethyl phosphonomethyl triflate (70) and base produced the N-phosphonomethylpyrrole 2-carboxylate 117, which was deprotected with trimethylsilyl bromide and saponified to the corresponding phosphonic acid 118. 

Finally, it should be emphasized here that some silylated intermediates, for example the subsequently described O-trimethylsilylated succinimide 202 a of silylated succinimide 201, are apparently silylated at higher temperatures to the very air-sensitive 0,0-bis(trimethylsilyl)sucdnimides (or 2,5-bis(trimethylsilyloxy)pyrroles)... 

Pyrroles can also be prepared by 1,3-dipolar cycloaddition of C-trimethylsilyl amides such as 1497 with dimethyl acetylenedicarboxylate in boihng toluene to give, via the azomethinimide 1498, 78% 1499 [45]. On employing a threefold excess of dimethyl acetylenedicarboxylate the cycloadduct 1499 is obtained in nearly quantitative yield [45] (Scheme 9.26). 

Incidentally, oxidation data of the pyrrole monomers show an interesting increase in oxidation potentials when containing heavier substituents (Table 25). However, the ionization potential of N -methylpyrrole (7.95 V) is smaller than that of pyrrole (8.21 V). The accepted linear relationship between ionization potential and oxidation potential210 would have it the other way round. Considering, however, that trimethylsilyl and trimethylgermyl groups are weak electron donors211, it is plausible that a nonelectronic effect is responsible for the observed trend and the potential shifts are associated with steric effects. 

To make tryptophan analogs, Gronowitz and coworkers conducted a pyrrole annulation from an aminoiodopyrimidine utilizing the Larock indole synthesis conditions (see Section 1.10.) [80]. They prepared heterocondensed pyrrole 115 by treating 4-amino-5-iodopyrimidine 114 with trimethylsilyl propargyl alcohol under the influence of a palladium catalyst The regiochemical outcome was governed by steric effects. 

DihydroindolesA novel synthesis of fused dihydroindoles involves [2 + 2 + 2]cycloaddition of alkynes with the 2,3-double bond of N-alkynoylated pyrroles. The reaction of 1 with bis(trimethylsilyl)ethyne results in two diaster-... 

Padwa et al. (75) found that the unsymmetrical miinchnone 137, which was generated from A-acetyl-7/-benzylglycine (136) and refluxing acetic anhydride, reacts with methyl propiolate to give an 8 1 mixture of pyrroles 138 and 139. The same product ratio is obtained from the reaction of methyl propiolate and the azomethine ylide derived from 7/-benzyl-A(-(a-cyanoethyl)-A(-[(trimethylsilyl)-methyl] amine. 

The participation of halopyrroles in Heck coupling is mostly limited to intramolecular transformations. In a recent example of intermolecular Heck reaction different A-protcctcd 3-iodo-4-trimethylsilyl-pyrroles were coupled... 

Secondary and tertiary aminoalkylbenzotriazoles (108) react with pyrrole, indole, and their N-methyl analogues under mild conditions in the presence of a Lewis acid to afford selectively the corresponding secondary or tertiary aminoalkyl derivatives (Scheme 22) (92T4971). A,A-Bis(alk-oxymethyl)amines can also be used to give secondary alkylamines, which operate via reactive iminium salts formed by treatment with trimethylsilyl chloride (90TL4229). 

A variety of pyrrole ring closure reactions are conveniently formulated as proceeding via nitrene intermediates, although it is doubtful whether a free nitrene is involved. Pyrolysis of o-nitrobiphenyls with iron(II) oxalate (61T(16)80), or reduction under milder conditions with triethyl phosphite (65JCS4831) or tris(trimethylsilyl) phosphite (79TL375), leads to the carbazole, as does the pyrolysis or photolysis of 2-azidobiphenyls (Scheme 3) (75JA6193). 

MO calculations67 on the trimethylsilylation of pyrrole and IV-alkylpyrroles have been reported in full and studies of sulfonation by S03 also pursued. Suggestions are made to reconcile the predictions as to regioselectivity with the experimentally observed /3-substitution in the reactions. 

Condensation of an MSMA isonitrile with an aroylfluoride gives a salt which undergoes loss of trimethylsilyl fluoride to form a nitrile ylid. This transient species reacts with DMAD to form 2-aroyl pyrrole in high yield.162 Substitution of acyl chloride for acyl fluoride in the reaction affords only poor yields of adducts.465... 

I he cycloaddition reactions generally give exo adducts with 1 -unsubstituted pyrroles, but 1 -methyl and 1 -trimethylsilyl substituents favor the endo stereoisomers. Cycloaddition has been achieved with. V-phenylmaleimide, methyl acrylate, methyl crotonate, dimethyl maleate, acrylonitrile and crotonitrile. The rate of cycloaddition is increased by 2,5-dimethyl substitution and this is attributed to the affect on the equilibrium between the 2,3 and 3,4-complexes. The isolation of azanorbornenes from the adducts by oxidative demetallation frequently leads to cycloreversion but azanorbornanes can be isolated by hydrogenation immediately after oxidation. <95JA3405>... 

---