Synthesis of Metal-Coordinating Arenediynes And Study Of Their Reactivity in Bergman Cyclization

The Bergman cycloaromatization (BC) in which a cis-alkene-1,2-diyne (enediyne) cyclizes to form a p-benzyne diradical, typically is a very endothermic reaction, requiring a substantial amount of energy (i.e. high temperature) for it to proceed. This reaction received very little attention until a decade after its discovery, when the natural enediynes were isolated and shown to be the most active antitumor agents every discovered. Having BC at the heart of their mode of action, these natural enediynes have been very challenging to mimic from synthetic standpoints. Of particular interest is to be able to design and synthesize an enediyne that is stable at room temperature, while also being capable of being triggered to undergo BC under ambient conditions. Although a relatively new concept, metal-induced BC reactions have generally been known to decrease the demanding energy barrier. The work presented here describes several synthetic strategies towards arenediyne crown eithers and the synthesis of several arenediyne hydrazone/Schiff base ligands with extended n-systems. These synthesized enediynes are useful ligands, capable of metal-cordination and hence potentially decreasing the BC energy barrier. BC reactions of enediyne intermediates are also reported.

Synthesis of Metal-Coordinating Arenediynes And Study Of Their Reactivity in Bergman Cyclization

The Bergman cycloaromatization (BC) in which a cis-alkene-1,2-diyne (enediyne) cyclizes to form a p-benzyne diradical, typically is a very endothermic reaction, requiring a substantial amount of energy (i.e. high temperature) for it to proceed. This reaction received very little attention until a decade after its discovery, when the natural enediynes were isolated and shown to be the most active antitumor agents every discovered. Having BC at the heart of their mode of action, these natural enediynes have been very challenging to mimic from synthetic standpoints. Of particular interest is to be able to design and synthesize an enediyne that is stable at room temperature, while also being capable of being triggered to undergo BC under ambient conditions. Although a relatively new concept, metal-induced BC reactions have generally been known to decrease the demanding energy barrier. The work presented here describes several synthetic strategies towards arenediyne crown eithers and the synthesis of several arenediyne hydrazone/Schiff base ligands with extended n-systems. These synthesized enediynes are useful ligands, capable of metal-cordination and hence potentially decreasing the BC energy barrier. BC reactions of enediyne intermediates are also reported.

Sterically hindering the trajectory of nucleophilic attack towards p-benzynes by a properly oriented hydrogen atom: An approach to achieve regioselectivity

Nucleophilic addition to p-benzynes, derived via Bergman Cyclization has become a topic of keen interest. Studying the regioselectivity in such addition can reveal important information regarding the parameters controlling such...

Bottom-up wet-chemical synthesis of a two-dimensional porous carbon material with high supercapacitance using a cascade coupling/cyclization route

A 2D porous carbon material with excellent electrochemical performance as an electrode in supercapacitors was synthesised using a Sonogashira–Hagihara cross-coupling/Bergman cyclization cascade reaction.

The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor

We present a contemporary mechanistic description of the light-driven conversion of cyclopropenone containing enediyne (CPE) precusors to ring-opened species amenable to further Bergman cyclization and formation of stable biradical species that have been proposed for use in light-induced cancer treatment. The transformation is rationalized in terms of (purely singlet state) Norrish type-I chemistry, wherein photoinduced opening of one C–C bond in the cyclopropenone ring facilitates non-adiabatic coupling to high levels of the ground state, subsequent loss of CO and Bergman cyclization of the enediyne intermediate to the cytotoxic target biradical species. Limited investigations of substituent effects on the ensuing photochemistry serve to vindicate the experimental choices of Popik and coworkers (J. Org. Chem., 2005, 70, 1297–1305). Specifically, replacing the phenyl moiety in the chosen model CPE by a 1,4-benzoquinone unit leads to a stronger, red-shifted parent absorption, and increases the exoergicity of the parent → biradical conversion.

Reaction selectivity of homochiral versus heterochiral intermolecular reactions of prochiral terminal alkynes on surfaces

Controlling selectivity between homochiral and heterochiral reaction pathways on surfaces remains a great challenge. Here, competing reactions of a prochiral alkyne on Ag(111): two-dimensional (2D) homochiral Glaser coupling and heterochiral cross-coupling with a Bergman cyclization step have been examined. We demonstrate control strategies in steering the reactions between the homochiral and heterochiral pathways by tuning the precursor substituents and the kinetic parameters, as confirmed by high-resolution scanning probe microscopy (SPM). Control experiments and density functional theory (DFT) calculations reveal that the template effect of organometallic chains obtained under specific kinetic conditions enhances Glaser coupling between homochiral molecules. In contrast, for the reaction of free monomers, the kinetically favorable reaction pathway is the cross-coupling between two heterochiral molecules (one of them involving cyclization). This work demonstrates the application of kinetic control to steer chiral organic coupling pathways at surfaces.