A Radical-Mediated Approach to the Total Synthesis of Fluorinated Marinoquinoline A and Related Tricyclic and Tetracyclic Congeners

Abstract

A radical-mediated approach to the core structure of fluorinated marinoquinoline A, N-methylated marinoquinoline A and related congeners via the use of Togni's reagent is described.

Crafting mono- and novel bis-methylated pyrroloquinoxaline derivatives from a shared precursor and its application in the total synthesis of marinoquinoline A

“…4a was prepared in a four-step procedure according to the literature in good yields. 19,28 A nucleophilic aromatic substitution between pyrrole and 2-uoronitrobenzene, followed by a reduction using Pd/C and hydrazine hydrate furnished amine 2a. Formylation, with ethyl formate and formic acid, followed by dehydration with phosphorus oxychloride in the presence of diisopropylamine resulted in the required cyclisation precursor 4a in excellent yield (Scheme 1).…”

“…18 Addition of alkyl groups have been recently reported to isocyanides to form 4-substituted pyrrolo[1,2-a]quinoxalines. [19][20][21][22][23][24][25] The methyl group is one of the most widespread functional groups in small biologically active molecules. Over the past decade, the methyl group has gained much interest in the pharmaceutical eld due to its ability to increase a drug's binding affinity and potency.…”

Recent Advances in the Trifluoromethylation Reactions of Isonitriles To Construct CF3-Substituted N-Heterocycles

“…In 2015, Hilton and Patel developed a radical-mediated approach to the total synthesis of the fluorinated marinoquinoline A, an N-heterocycle containing the quinoline core. 24 N -Protected 3-(2-isocyanophenyl)-1 H -pyrroles were selected as starting materials and subjected to the trifluoromethylation/cyclization conditions reported previously by Studer 11 using Togni’s reagent I and tetramethylammonium iodide (TMAI) as the iodine source/initiator to generate the CF 3 radical. Attack of this radical onto the carbon atom of the isonitrile functionality followed by 6- endo cyclization afforded the desired tricyclic structures bearing a trifluoromethyl group at C2 of the quinoline ring in moderate yields (Scheme 13 ).…”