title: Ring opening versus ring expansion in rearrangement of bicyclic cyclobutylcarbinyl radicals.
abstract: Ring opening and expansion of multicyclic cyclobutylcarbinyl radicals provides an appealing method for the construction of heavily substituted ring systems in a stereocontrollable fashion. Here we conducted the first, systematic study on the regioselectivity in the rearrangement of various synthetically relevant cyclobutylcarbinyl radicals. It was found that a two-layer ONIOM method, namely ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(2df,2p)), could accurately predict the free energy barriers of the ring openings of cyclobutylcarbinyl radicals with a precision of 0.3 kcal/mol. By using this powerful tool we found that the regiochemistry for the ring opening of monocyclic cyclobutylcarbinyl radicals could be easily predicted by the relative stability of the two possible carbon radical products. A linear correlation was found between the activation and reaction free energies. This observation indicated that the ring opening of cyclobutylcarbinyl radicals was strongly affected by the thermodynamic factors. On the basis of the above results we extended our study to the rearrangement of bicyclic cyclobutylcarbinyl radicals that could undergo both ring opening and expansion. It was found that for bicyclic cyclobutylcarbinyl radicals whose radical center was located at the bridge methyl group, ring expansion was the favored rearrangement pathway unless a strongly radical-stabilizing substituent was placed in the cyclobutyl ring adjacent to the bridge methyl group. On the other hand, for bicyclic cyclobutylcarbinyl radicals whose radical center was located at the 2-position, ring opening was the favored rearrangement pathway unless a strongly radical-stabilizing substituent was placed in the cyclobutyl ring at the bridge position.
authors.affiliation: Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Chong
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.forename: Qing-Xiang
authors.initials: QX
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D003503:Cyclobutanes / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006536:Heptanes / Q000737:chemistry; D006586:Hexanes / Q000737:chemistry; D000432:Methanol / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D001643:Bridged Bicyclo Compounds; D003503:Cyclobutanes; D005609:Free Radicals; D006536:Heptanes; D006586:Hexanes; C490696:cyclobutylcarbinol; D000432:Methanol