Automated generation and reactions of 3-hydroxymethylindoles in continuous-flow microreactors.
An automated sequential approach for the generation and reactions of 3-hydroxymethylindoles in continuous-flow microreactors is described. Consecutive halogen-magnesium exchanges of four 3-iodoindoles followed by addition to three aldehydes provided twelve 3-hydroxymethylindoles in a multi-microreactor setup. The synthetic flow strategy could be coupled with an in line continuous liquid-liquid extraction workup protocol for each reaction. Further elaboration of each of these indoles within the fluidic setup was achieved by acid-catalysed nucleophilic substitutions with allyltrimethylsilane and methanol used as nucleophiles. Overall, a set of four 3-iodoindoles was converted into thirty-six indole derivatives by a range of transformations including iodo-magnesium exchange/electrophile trapping and acid-catalysed nucleophilic substitution in a fully automated sequential fashion.
Tricotet
Thomas
T
Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland.
O'Shea
Donal F
DF
D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D006219:Halogens / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D015394:Molecular Structure; D055585:Physical Phenomena
D000447:Aldehydes; D006219:Halogens; D007211:Indoles; C016517:indole-3-carbinol; D008274:Magnesium