The development and application of novel methods for accomplishing the synthesis of heterocycles ... more The development and application of novel methods for accomplishing the synthesis of heterocycles via osmium-catalyzed oxidative cyclization onto an alkene is described in this Perspective. Beginning with a fortuitous discovery, an extensive examination of the possible mechanism of cyclization has been carried out, and the method was continuously developed until it had been transformed into an extremely efficient and powerful new catalytic reaction for the formation of tetrahydrofurans and pyrrolidines with complete control over all aspects of relative and absolute stereochemistry. By working with Os(VI) rather than the more familiar Os(VIII), a highly potent yet mild set of reaction conditions were developed. In addition to the method development studies, this work also sets out some synthetic challenges against which the methodology was tested. Pleasingly, the catalytic oxidative cyclization has proved itself to be an efficient and functional group tolerant process that was pivotal to the completion of several natural product syntheses.
First, the electrochemical characteristics of Fenton's reagent (Fe (III), Fe (II) and hydrog... more First, the electrochemical characteristics of Fenton's reagent (Fe (III), Fe (II) and hydrogen peroxide), including its catalytic (EC0) behaviour were investigated. Second, the electrogeneration of hydrogen peroxide by a two-electron reduction of dissolved oxygen was conducted at a carbon electrode in a divided electrolysis cell and the concentration of hydrogen peroxide obtained was determined by the titration. The two approaches were then combined to give a one-pot, relatively green approach to aromatic hydroxylation reactions, ...
ABSTRACT A variety of tetrahydrofurans bearing a silyl group at the ring junction is prepared in ... more ABSTRACT A variety of tetrahydrofurans bearing a silyl group at the ring junction is prepared in good yields stereoselectively via a osmium-catalyzed oxidative cyclization of appropriate terminal vinyl silanes.
The metal-promoted dehydrogenation of cyclic thioethers S(C(5)H(9))(R) (R = C(5)H(9), Ph) to give... more The metal-promoted dehydrogenation of cyclic thioethers S(C(5)H(9))(R) (R = C(5)H(9), Ph) to give the corresponding cycloalkenes, S(C(5)H(7))(R), using the [Rh{Ph(2)P(CH(2))(3)PPh(2)}](+) fragment is reported.
A novel osmium-catalysed oxidative cyclisation of 1,2-diols bearing a pendant vinyl silane afford... more A novel osmium-catalysed oxidative cyclisation of 1,2-diols bearing a pendant vinyl silane affords THFs that contain silicon functionality at the ring junction. When the cyclisation occurs onto a vinyl benzyldimethylsilyl group, the resulting silyl group can act as a masked hydroxyl group and undergo a Fleming-Tamao type oxidation at a later stage to form the corresponding lactol. The scope of this reaction can also be extended beyond 1,2-diols and applied to the cyclisation of α-hydroxy-sulfonamides and α-hydroxy-amides.
The development and application of novel methods for accomplishing the synthesis of heterocycles ... more The development and application of novel methods for accomplishing the synthesis of heterocycles via osmium-catalyzed oxidative cyclization onto an alkene is described in this Perspective. Beginning with a fortuitous discovery, an extensive examination of the possible mechanism of cyclization has been carried out, and the method was continuously developed until it had been transformed into an extremely efficient and powerful new catalytic reaction for the formation of tetrahydrofurans and pyrrolidines with complete control over all aspects of relative and absolute stereochemistry. By working with Os(VI) rather than the more familiar Os(VIII), a highly potent yet mild set of reaction conditions were developed. In addition to the method development studies, this work also sets out some synthetic challenges against which the methodology was tested. Pleasingly, the catalytic oxidative cyclization has proved itself to be an efficient and functional group tolerant process that was pivotal to the completion of several natural product syntheses.
First, the electrochemical characteristics of Fenton's reagent (Fe (III), Fe (II) and hydrog... more First, the electrochemical characteristics of Fenton's reagent (Fe (III), Fe (II) and hydrogen peroxide), including its catalytic (EC0) behaviour were investigated. Second, the electrogeneration of hydrogen peroxide by a two-electron reduction of dissolved oxygen was conducted at a carbon electrode in a divided electrolysis cell and the concentration of hydrogen peroxide obtained was determined by the titration. The two approaches were then combined to give a one-pot, relatively green approach to aromatic hydroxylation reactions, ...
ABSTRACT A variety of tetrahydrofurans bearing a silyl group at the ring junction is prepared in ... more ABSTRACT A variety of tetrahydrofurans bearing a silyl group at the ring junction is prepared in good yields stereoselectively via a osmium-catalyzed oxidative cyclization of appropriate terminal vinyl silanes.
The metal-promoted dehydrogenation of cyclic thioethers S(C(5)H(9))(R) (R = C(5)H(9), Ph) to give... more The metal-promoted dehydrogenation of cyclic thioethers S(C(5)H(9))(R) (R = C(5)H(9), Ph) to give the corresponding cycloalkenes, S(C(5)H(7))(R), using the [Rh{Ph(2)P(CH(2))(3)PPh(2)}](+) fragment is reported.
A novel osmium-catalysed oxidative cyclisation of 1,2-diols bearing a pendant vinyl silane afford... more A novel osmium-catalysed oxidative cyclisation of 1,2-diols bearing a pendant vinyl silane affords THFs that contain silicon functionality at the ring junction. When the cyclisation occurs onto a vinyl benzyldimethylsilyl group, the resulting silyl group can act as a masked hydroxyl group and undergo a Fleming-Tamao type oxidation at a later stage to form the corresponding lactol. The scope of this reaction can also be extended beyond 1,2-diols and applied to the cyclisation of α-hydroxy-sulfonamides and α-hydroxy-amides.
Uploads
Papers by Ben Pilgrim