title: Synthetic studies towards putative yuremamine using an iterative C(sp(3))-H arylation strategy.
abstract: An overview of an iterative, 8-aminoquinoline (AQ)-directed C(sp(3))-H arylation strategy towards the pyrroloindole structure initially assigned to the alkaloid yuremamine is described. During initial efforts using a model indane system, it was discovered that the iodoresorcinol unit was not a viable C(sp(3))-H arylation partner when masked as its dimethyl ether but upon switching to a MOM group, the ether oxygen served to stabilise the high valent Pd intermediate during the reaction, thus promoting reductive elimination and leading to acceptable yields of the C(sp(3))-H arylation product. The second C(sp(3))-H arylation with an iodopyrogallol gave a 1,3-diarylated model yuremamine system possessing the desired 1,3-cis relationship. When the successful model studies were applied to a pyrroloindole system in pursuit of yuremamine, it became apparent that C9 underwent competing C(sp(2))-H arylation if left vacant, but installing a tryptamine side chain at this site prevented the desired C(sp(3))-H arylation from occurring altogether. However, a C9-methyl pyrroloindole underwent iterative C(sp(3))-H arylation at C1 with an iodoresorcinol followed by C3 with an iodopyrogallol to give a diarylated product with the aryl groups in the undesired 1,3-trans-relationship, arising from epimerisation at C1 during the second C(sp(3))-H arylation event. Although the synthesis of putative yuremamine was not accomplished, several findings are disclosed that will serve as useful additions to the burgeoning field of directed C(sp(3))-H arylations and related C-H functionalization reactions.
authors.affiliation: School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland, New Zealand. j.sperry@auckland.ac.nz.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Calvert
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sperry
mesh_terms: D001554:Benzene / Q000737:chemistry; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D010936:Plant Extracts / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D007211:Indoles; D010936:Plant Extracts; C507332:Yuremamine; D010165:Palladium; D001554:Benzene