ABSTRACT
An oxidative radical cascade addition cyclization approach for the synthesis of quinoline-based π-extended polyheterocyclic compounds is reported. Eco-friendly iron catalysis and inexpensive tert-butylhydroperoxide (TBHP) as the oxidant have been utilized in the transformation of various readily available ortho-alkynylated aromatic aldehydes as radical precursors with aryl isonitriles as radical acceptors. Indole and thiophene-based carbaldehydes allow the preparation of quinolines that are π-conjugated with an additional heteroarene moiety in a single sequence by applying the introduced method.
ABSTRACT
(-)-Galanthamine as a drug for the treatment of Alzheimer's disease has attracted synthetic chemists for decades. However, previous total synthetic and biomimetic approaches often use stoichiometric oxidants (metal oxidants or hypervalent iodine) to prepare the target product. Anodic oxidative coupling offers a sustainable alternative method which is, for the first time, successfully applied to the total synthesis of (-)-galanthamine. We report a new asymmetric total synthesis of (-)-galanthamine by using an anodic aryl-phenol coupling as the key synthetic step.
Subject(s)
Galantamine , Phenol , Biomimetics , Oxidants , PhenolsABSTRACT
A radical cascade to 2,3-disubstituted indoles proceeding via acylation or trifluoromethylation of ortho-alkynylphenyl isonitriles is presented. In these cascades, two C-C bonds and one C-O bond are formed using an inexpensive oxidant and a catalytic copper or iron salt. The starting isonitriles are easily accessible, and commercially available aldehydes and fluoromethylation reagents serve as reaction partners. Functional group tolerance is high, as documented by the successful preparation of a series of 2,3-disubstituted indoles.
