Clean five-step synthesis of an array of 1,2,3,4-tetra-substituted pyrroles using polymer-supported reagents

Abstract

Polymer-supported reagents and other solid sequestering agents may be used to generate an array of 1,2,3,4-tetra-substituted pyrrole derivatives without any chromato-graphic purification step.

References

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7. Prepared by filtering an aqueous solution of potassium permanganate through Amberlyst A-27, subsequent washing of the obtained brick-red material with water and acetone and drying of the beads in vacuo.
8. The utilisation of Amberlyst A-21 for a similar reaction has been described (G. Rosini, R. Ballini and M. Petrini, Synthesis, 1986, 46), but this ion exchange resin proved to be not very efficient in our hands. Instead of Amberlite IRA-420 (OH-form), DOWEX-1 (OH-form) can be used.
9. Without an excess or in absence of the nitromethylene compound Amberlite IRA-420 (OH-form) can effect a Cannizzaro reaction of electron-poor benzaldehydes. In combination with a solid supported oxidant to reoxidise the benzylic alcohols to the aldehydes, this reaction can be used to generate benzoic acids.
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11. TBD on polystyrene was 2.2 mmol g^–1 and purchased from Fluka. In the reaction 1.1 equiv. of the isocyanide and 2 equiv. of the base were used.
12. BEMP on polystyrene was 2.3 mmol g^–1 and purchased from Fluka. In the reaction 5 equiv. of the alkyl halide and 20 equiv. of the base were used.
13. W. Xu, R. Mohan and M. M. Morrissey, Bioorg. Med. Chem. Lett., 1998, 8, 1089 The benzylation and the allylation of the pyrrole system was not sufficiently fast enough to compete with the attack on the pyridine moiety, which led to substantial side reactions in these two cases.
14. P. Hodge and G. Richardson, J. Chem. Soc., Chem. Commun., 1975, 622 The transformation of the alcohol with bromotrichloromethane resulted in a mixture of alkyl bromide and alkyl chloride (average ratio 3∶5), which also could be used directly for the alkylation reaction.