Regioselective synthesis of acylpyrroles

Abstract

The regioselective synthesis of several pyrrole derivatives is described. AlCl3-catalyzed acylation reactions of l-(phenylsulfonyl)pyrrole (1) give 3-acyl derivatives, whereas the corresponding BFg-OEts-catalyzed reactions give 2-acyl derivatives predominantly. Mild alkaline hydrolysis gives the corresponding acyl-lR-pyrroles in excellent yields. AlCl3-catalyzed reactions of 1 with 1,1-dichloromethyl methyl ether and oxalyl chloride give l-(phenylsulfonyl)-2-formylpyrrole (6) and l-(phenylsulfonyl)-2-(chlorocarbonyl)pyrrole (7), respectively. 3-Pyrrolylacetic acid (10) was prepared by thallium(III) nitrate promoted rearrangement of 1 -(phenylsulfonyl)-3-acetylpyrrole (2a). Trifluoroacetic anhydride catalyzed cyclization of 4-[ 1 -(phenylsulfonyl) -3-pyrrolyl] butyric acid ( 14) gives l-(phenylsulfonyl)-7-oxo-4,5,6,7-tetrahydroindole (17). Attempts to cyclize 14 at the 4-position have been unsuccessful.

Positional selectivity in reactions of pyrrole and its N-substituted derivatives with electrophiles

“…8,11 In contrast, nitration (HNO 3 −Ac 2 O) proceeds almost exclusively in the 3-position. 10 As was established recently, the same orientation applies to the sulfonation of unsubstituted pyrrole and N-methylpyrrole with pyridine sulfotrioxide. 16 The differences in orientation given above are usually interpreted within the framework of the HSAB principle: the orientation for a "hard" electrophile is determined mainly by negative charge in position 3, while the substitution in position 2 in the case of "softer" electrophiles is the result of orbital control.…”

“…The effect of the N-phenylsulfonyl substituent was studied in detail. This substituent was simultaneously offered by two groups of researchers [8][9][10][11] as an original protecting group that owing to its electron-withdrawing effect deactivates preferably the α-position and allows one to obtain β-substituted derivatives, the PhSO 2 group being readily removed on alkaline hydrolysis. 10 The effect of the PhSO 2 group was studied in most detail for Friedel−Crafts acylation.…”

“…This substituent was simultaneously offered by two groups of researchers [8][9][10][11] as an original protecting group that owing to its electron-withdrawing effect deactivates preferably the α-position and allows one to obtain β-substituted derivatives, the PhSO 2 group being readily removed on alkaline hydrolysis. 10 The effect of the PhSO 2 group was studied in most detail for Friedel−Crafts acylation. [8][9][10][11][12][13][14][15] The role of the nature of the reagent reveals itself most distinctly in the fact that in the presence of aluminum chloride the 3-acylsubstituted derivatives are obtained, while reaction in the presence of boron trifluoride etherate gives the 2-isomers 10 (Scheme 2).…”

“…10 The effect of the PhSO 2 group was studied in most detail for Friedel−Crafts acylation. [8][9][10][11][12][13][14][15] The role of the nature of the reagent reveals itself most distinctly in the fact that in the presence of aluminum chloride the 3-acylsubstituted derivatives are obtained, while reaction in the presence of boron trifluoride etherate gives the 2-isomers 10 (Scheme 2).…”

Oxidative radical cyclization to pyrroles under reducing conditions. Reductive desulfonylation of α-sulfonylpyrroles with tri-n-butyltin hydride

“…After 20 min at this temperature, this mixture was added to a stirred solution of 3-benzoylpyrrole (ref. 16,6.0 g, 35 mrnol) in rnethan01 at -78°C. The reaction mixture was warmed to 4 0°C and after 0.5 h it was poured into water.…”