A simple and efficient route to β-substituted pyrroles

Synthetic studies related to the akuammiline alkaloids

“…Of various routes to 4-acetyl-2-benzoylpyrrole 16 we found the best was to start with 3-acetylpyrrole, itself available via Friedel-Crafts acetylation of 1-phenylsulfonylpyrrole, then de-N-protection; 40 The further development of this successful route, to provide an appropriate bicycle for the alkaloid synthesis, required that the benzenoid ring carry an ortho nitrogen substitutent. We reacted the 2-lithio-1-phenylsulfonylpyrrole with ortho-nitrobenzaldehyde, then immediately oxidised the resulting mixture, but were only able to obtain a 10% yield of ketone 20.…”

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

“…It is important to note that 1-(phenylsulfonyl)pyrrole gives only 2-substituted derivatives on both Rieche formylation with alkyl dichloromethyl ethers 8,9 and Vilsmeier formylation in the DMF−POCl 3 system, 8 as well as on cyanation with cyanogen bromide in the presence of AlCl 3 or with chlorosulfonyl isocyanate. 8,11 In contrast, nitration (HNO 3 −Ac 2 O) proceeds almost exclusively in the 3-position.…”

“…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. 9 The high efficiency of the N-triisopropylsilyl substituent used as another "protective" group for the preparation of β-substituted pyrroles is based, as proposed in Ref. 17, on steric shielding of α-positions.…”

“…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.…”

“…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).…”