Controlling the regiochemistry of radical cyclizations.
This review describes the results of our recent studies on the control of the regiochemistry of radical cyclizations. N-vinylic alpha-chloroacetamides generally cyclized in a 5-endo-trig manner to give five-membered lactams, whereas 4-exo-trig cyclization occurred when the cyclized radical intermediates were highly stabilized by an adjacent phenyl or phenylthio group to afford beta-lactams. The 5-exo or 6-exo cyclization of aryl radicals onto the alkenic bond of enamides could be shifted to the corresponding 6-endo or 7-endo mode of cyclization by a positional change of the carbonyl group of enamides. The 6-endo- and 7-endo-selective aryl radical cyclizations were applied to radical cascades for the synthesis of alkaloids such as phenanthroindolizidine, cephalotaxine skeleton, and lennoxamine. The 5-exo-trig cyclization of an alkyl radical onto the alkenyl bond of enamides could also be shifted to the 6-endo mode by a positional change of the carbonyl group of enamides. The 6-endo- selective cyclization was applied to the radical cascade to afford a cylindricine skeleton. Other examples of controlling the regiochemistry of radical cyclizations and their applications to the synthesis of natural products are also discussed.
Ishibashi
Hiroyuki
H
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. isibasi@p.kanazawa-u.ac.jp
D000470:Alkaloids / Q000138:chemical synthesis; D001688:Biological Products / Q000138:chemical synthesis; D003500:Cyclization; D004146:Dioxanes / Q000138:chemical synthesis; D005609:Free Radicals / Q000737:chemistry; D006248:Harringtonines / Q000138:chemical synthesis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D000077863:Homoharringtonine; D007769:Lactams / Q000138:chemical synthesis; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis*
D000470:Alkaloids; D001688:Biological Products; D004146:Dioxanes; D005609:Free Radicals; D006248:Harringtonines; D006571:Heterocyclic Compounds; D007769:Lactams; D011083:Polycyclic Compounds; C442893:lennoxamine; D000077863:Homoharringtonine