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Organotin reagents in synthesis : efficient syntheses of Z-stilbenes, phenanthrenes, helicenes and azahelicenes

Organotin reagents in synthesis : efficient syntheses of Z-stilbenes, phenanthrenes, helicenes and azahelicenes
Organotin reagents in synthesis : efficient syntheses of Z-stilbenes, phenanthrenes, helicenes and azahelicenes

High cis-selectivities have been achieved when forming stilbenes using a Wittig reaction between an aldehyde and phosphonium salt, in cases where each component bears an ortho-halo- or ortho-methoxy-substituent.  This effect is more pronounced when one or both of the aromatic rings are electron-rich.  Its usefulness has been exemplified in a high yielding synthesis of combretastatin A-4.

We additionally report that cis-2,2’-dihalostilbenes, when subjected to tin mediated radical cyclisation conditions, undergo cyclisation to form a phenanthrene.  The new carbon to carbon bond is formed between the ortho-carbon bearing the weakest bound halogen and the unsubstituted ortho-carbon on the adjacent aromatic ring. Thus, the halide acts as both a stereocontrolling element in the Wittig reaction and as a protecting/directing group to control regiochemistry in the cyclisation step.  The methodology has been exploited in the synthesis of substituted phenanthrenes, [5]- and [7]helicenes and azahelicenes providing a high yielding entry to such materials via a course that can be predicted at the outset.

A new combination reagent, hexabutylditin and tetra-n-butylammonium fluoride, is also described, together with its use in the reduction and deuteration of aryl bromides and iodides.  In addition, work on the removal of organotin residues by the use of 10% w/w potassium carbonate (or fluoride) and 90% w/w silica is discussed.  Each has been shown to be  highly effective for the chromatographic removal of organotin impurities from tributyltin hydride mediated reduction and cyclisation procedures achieving levels below 30 ppm tin impurities.

University of Southampton
Guy, Ian Lloyd
Guy, Ian Lloyd

Guy, Ian Lloyd (2005) Organotin reagents in synthesis : efficient syntheses of Z-stilbenes, phenanthrenes, helicenes and azahelicenes. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

High cis-selectivities have been achieved when forming stilbenes using a Wittig reaction between an aldehyde and phosphonium salt, in cases where each component bears an ortho-halo- or ortho-methoxy-substituent.  This effect is more pronounced when one or both of the aromatic rings are electron-rich.  Its usefulness has been exemplified in a high yielding synthesis of combretastatin A-4.

We additionally report that cis-2,2’-dihalostilbenes, when subjected to tin mediated radical cyclisation conditions, undergo cyclisation to form a phenanthrene.  The new carbon to carbon bond is formed between the ortho-carbon bearing the weakest bound halogen and the unsubstituted ortho-carbon on the adjacent aromatic ring. Thus, the halide acts as both a stereocontrolling element in the Wittig reaction and as a protecting/directing group to control regiochemistry in the cyclisation step.  The methodology has been exploited in the synthesis of substituted phenanthrenes, [5]- and [7]helicenes and azahelicenes providing a high yielding entry to such materials via a course that can be predicted at the outset.

A new combination reagent, hexabutylditin and tetra-n-butylammonium fluoride, is also described, together with its use in the reduction and deuteration of aryl bromides and iodides.  In addition, work on the removal of organotin residues by the use of 10% w/w potassium carbonate (or fluoride) and 90% w/w silica is discussed.  Each has been shown to be  highly effective for the chromatographic removal of organotin impurities from tributyltin hydride mediated reduction and cyclisation procedures achieving levels below 30 ppm tin impurities.

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Published date: 2005

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Local EPrints ID: 466740
URI: http://eprints.soton.ac.uk/id/eprint/466740
PURE UUID: 25bc5686-1c6e-4a4b-820b-709e09a14e7c

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Date deposited: 05 Jul 2022 06:32
Last modified: 05 Jul 2022 06:32

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Author: Ian Lloyd Guy

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