Pyrroles 1-triisopropylsilyl

Pyrroles and indoles can be protected with the r-butyldimethylsilyl group by treatment with TBDMSCl and n-BuLi or NaH. Triisopropylsilyl chloride (NaH, DMF, 0°-rt, 73% yield) has been used to protect the pyrrole nitrogen in order to direct electrophilic attack to the 3-position.It has also been used to protect an indole.This derivative can be prepared from the silyl chloride and The silyl protective group is cleaved with Bu4N F , THF, rt or with CF3COOH. 

The same methodology can also be used for the sequential replacement of the two bromine atoms in 3,4-dibromo-l-(triisopropylsilyl)pyrrole, and a variety of different disubstituted derivatives have now been prepared (84HCA1168 90TL6785). An example is shown by the synthesis of verru-carin E (Scheme 16) (84HCA1168 90JOC6317). 

Bromo-l-(triisopropylsilyl)pyrrole undergoes initial reaction with butyllithium followed by reaction with A -fluorobis(phenylsulfonyl)amine (la) to give 3-fluoro-l-(triisopropylsilyl)pyr-role (8).144... 

Reactions of pyrrole or 1-methylpyrrole with N-aroylbenzotriazoles (ArCO = 4-MeCgH4CO, 4-O2NC6H4CO, 4-Et2NC6H4CO, 2-furoyl, 2-pyridoyl, 2-indolcarbonyl, 2-pyrroloyl) in the presence of TiCU afford 2-acylpyrroles in yields from 21% to 94%. In contrast, l-(triisopropylsilyl) pyrrole under the same conditions gives the corresponding 3-acyl-substituted pyrroles (03JOC5720). 

Using another approach, starting from the pyrrole core <04TL0000> syntheses of lamellarins Q and O were also achieved. In this work, the methyl A -(triisopropylsilyl)-3,4-dibromopyrrole-2-carboxylate 102 was used as the initial scaffold. Banwell et al. <97CC207> used the dibromopyrrole 102 in an elegant convergent synthesis of several compounds from this family of marine alkaloids (shown above). 

Metal-halogen exchange using 3-halo-iV-triisopropylsilyl-pyrroles allows the introduction of groups to the pyrrole p-position and can complement direct electrophilic substimtion of iV-triisopropylsilylpyrrole, which is p-selective (see 16.1.2 and 16.1.4). Sequential mono-Uthiations of l-tosyl-3,4-dibromopyrrole allows selective functionalisation. ... 

Very electron-rich aromatic systems interact with acid chlorides and anhydrides in the absence of a catalyst to afford good yields of ketones. Reactions of pyrrole and substituted pyrroles exemplify these reactions. The oxalylation shown in equation (18) was part of the synthesis of a complex, highly functionalized antitumor agent. Use of the triisopropylsilyl group to direct reaction to the 3-position (equation 19) is noteworthy. ... 

Tribromination of A -(triisopropylsilyl)pyrrole with NBS followed by TBAF deprotection provided a regioselective synthesis of 2,3,5-tribromopyrrole, an natural occurring antifeedant from the marine worm Saccoglossus kowalevskii <04JNP1929>. 

V-Substitution of pyrroles gives rise to increased proportions of yS-substitution, even methyl causing the (3 a ratio to change to 1 3, the much larger t-butyl actually reverses the relative positional reactivities, with a (3 a ratio of 4 1, and the intrinsic a-reactivity can be effectively completely blocked with a very large substituent such as a triisopropylsilyl (TIPS) group, especially useful since it can be subsequently easily removed. ... 

In terms of C-3 substitution reactions, the regioscleclive borylation of 1-triisopropylsilyl-pyrrole (77) was achieved providing a valuable reagent for cross-coupling reactions <01OL2831>. Thus, reaction of 77 with the rhodium precatalyst shown in the presence of pinacolborane affords the C-3 substituted derivative 78. 

This catalytic oxidative annulalion process can also be applied to pyrrole systems. Gaunt and coworkers [29] had described the intermolecular selective alkenylation of C(2) or C(3) of pyrroles based on the nitrogen protecting group (Scheme 9.5 see above). This same concept was implemented in an intramolecular sense to achieve selective annula-tions (Scheme 9.23). When iV-tosyl pyrrole 168 was subjected to oxidative conditions, the cyclization occurred at C(2) to form pyrrole 169. Alternatively, when structurally similar N-triisopropylsilyl pyrrole 170 was treated with the same palladium(II) system, the functionalization occurred at C(4) to afford pyrrole 171. This intriguing differentiation based on the choice of protecting group could have broad implications in selective functionalizations of heterocycles. 

An alteration of the directing effect for SjAr is observed when (1-triisopropylsilyl) pyrrole (7) is subjected to halogenation and nitration [103] ... 

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