Bergman Cyclization of Sterically Hindered Substrates and Observation of Phenyl-Shifted Products M1...
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Transcript of Bergman Cyclization of Sterically Hindered Substrates and Observation of Phenyl-Shifted Products M1...
Bergman Cyclization of Sterically Hindered Substratesand Observation of Phenyl-Shifted Products
M1 Colloquiumin Division Frontier Materials Science in 2005
Tobe LaboratoryHiroyuki Kuge
Kevin D. Lewis, and Adam J. Matzger*
J. Am. Chem. Soc. 2005, 127, 9968.
sterically hindered: 立体的に込み合ったsubstrate: 基質
Contents
1. Introduction
2. Experiment
4. Summary
3. Results and Discussion
1 2
What is the “Bergman Cyclization” ?
In 1972, Bergman and co-workers founded thatdeuteration compound 1 interconverts only 2and the process that leads to the formation ofaromatic 1,4-diradical system as intermediate
Enediyne have a C-C double bond and two C-C triple bonds
The intermediate produces benzene in presence of hydrogen radical donor intermediate: 中間体
Mechanism of DNA Cleavage by Calicheamicin
Calicheamicin is an very potent antitumor agent. It has an endiyne moiety and readily cyclize,forming a highly reactive 1,4-benzenediradical intermediate.This radical can oxidatively cleave DNA.
Bergman cyclization has been very availableIsomerization that has found applications in areas ranging from drug design to materials synthesis
antitumor agent: 抗がん剤
Expected Cyclization of 1,2-bis(phenylethynyl)benzene
Products of Thermal Reaction of 1,2-Bis(phenylethynyl)benzene in benzene
Plausible Mechanism of Radical Species
B C
F
D E
Products of Bergman Cyclization in hidered system
Possibility of transform from 2,3-diphenylnaphthalene to 1,3- and 1,4-diphenylnaphthalene
14.5 kcal/mol
42.9 kcal/mol
The Barrier to Formation of the Transition State
in the case of phenyl shift onto the sp3 radical
in the case of phenyl shift onto the sp2 radical
Front view
Modeled by MM2 calc.
Side view
Bird’s-eye view
The view of 2,3-diphenylnaphthalene
Stability of Benzene Diradical Isomers
Stability of Naphthalene Diradical Isomers
Stability of Disubstitued Naphthalene Diradical Isomers ?
Proposed Mechanism of Cyclization of 1,2-Bis(phenylethynl)benzene
Proposed Mechanism of Cyclization of1-phenylethynl-2-ethynylbenzene
The Mechanism of “Phenyl Walking”
studies on a derivative of 2,3-diphenylehynylbenzene in which the phenyl rings wereperdeuterated confirmed that no deuterium transfer to the naphthalene ring occurred
thus ruling out this phenyl shifting mechanism
Summary
The study of particularly hindered Bergman cyclizations revealed that phenyl shifts can dominate the products formed under certain conditions.
Relief of steric hindrance and formation of more energetically favorablebenzenediradicals will lead to a lowering of the barrier.