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.