Synthesis of heteroarenes using cascade radical cyclisation via iminyl radicals.
Cascade radical cyclisation involving homolytic aromatic substitution has been used to synthesise new tetracycles. Treatment of vinyl iodide radical precursors with Me(3)Sn. radicals (from hexamethylditin) yielded intermediate vinyl radicals which undergo 5-exo cyclisation onto suitably placed nitrile groups to yield intermediate iminyl radicals. The iminyl radicals undergo aromatic homolytic substitution via 6-endo cyclisation (or 5-exo cyclisation followed by neophyl rearrangement) with loss of hydrogen (H.) in a H-abstraction step. We propose that this abstraction was facilitated by tert-butoxyl (t-BuO.) radicals from di-tert-butyl peroxide or methyl radicals, generated from breakdown of trimethylstannyl radicals (Me(3)Sn.). The biologically active alkaloids mappicine and luotonin A were synthesised using the new methodology. A novel radical conversion of nitriles to primary amides is proposed.
Bowman
W Russell
WR
Department of Chemistry, Loughborough University, Leicestershire, UK. w.r.bowman@lboro.ac.uk
Cloonan
Martin O
MO
Fletcher
Anthony J
AJ
Stein
Tobias
T
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D007094:Imides / Q000737:chemistry*; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry; D011809:Quinones / Q000138:chemical synthesis / Q000737:chemistry
D000470:Alkaloids; D005609:Free Radicals; D007094:Imides; D007212:Indolizines; D011758:Pyrroles; D011804:Quinolines; D011809:Quinones; C480761:luotonin A; C008325:mappicine; C414097:nothapodytine B