Substituent effects on the rearrangements of cyclohexyl to cyclopentyl radicals involving avermectin-related radicals.
The rearrangement of a substituted cyclohexyl radical to a cyclopentylmethyl radical on the skeleton of avermectin B1 has been investigated using density functional (UB3LYP/6-31G(d)) and G3MP2B3 computational methods. The rearrangement is preferred when highly radical stabilizing groups are present at the 2- and 3-positions of the cyclohexyl radical. A substituent on the 3-position of the cyclohexyl radical enables ring-cleavage of the cyclohexyl radical, while a radical stabilizing substituent on the 2-position of the cyclohexyl radical stabilizes the final cyclopentylmethyl radical, enabling the overall rearrangement and reversing the normal thermodynamic preference for the hexenyl radical ring closure.
Luft
Jennifer A R
JA
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
Winkler
Tammo
T
Kessabi
Fiona M
FM
Houk
K N
KN
D003510:Cyclohexanes / Q000737:chemistry*; D003517:Cyclopentanes / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D013816:Thermodynamics
D003510:Cyclohexanes; D003517:Cyclopentanes; D005609:Free Radicals; D007559:Ivermectin; C019264:avermectin