Anodic Cyclizations, Densely Functionalized Synthetic Building Blocks, and the Importance of Recent Mechanistic Observations.

Anodic cyclization reactions can provide a versatile method for converting newly obtained chiral lactols to densely functionalized cyclic building blocks. The method works by first converting the lactol into an electron-rich olefin and then oxidatively generating a radical cation that is trapped by a nucleophile. Historically, such reactions have benefited from the use of less polar radical cations when the trapping nucleophile is a heteroatom and more polar radical cations when the reaction forms C-C bonds. This forced one to optimize underperforming reactions by resynthesizing the substrate. Here, we show that by taking advantage of methods that serve to drive a reversible initial cyclization reaction toward the product, this dichotomy and need to manipulate the substrate can be avoided. Two such methods were utilized: a faster second oxidation step and a mediated electrolysis. Both led to successful cyclizations using a polar radical cation and heteroatom nucleophiles.

Lessons from an Array: Using an Electrode Surface to Control the Selectivity of a Solution-Phase Chemical Reaction.

Electrochemistry offers a variety of novel means by which selectivity can be introduced into synthetic organic transformations. In the work reported, it is shown how methods used to confine chemical reactions to specific sites on a microelectrode array can also be used to confine a preparative reaction to the surface of an electrode inserted into a bulk reaction solution. In so doing, the surface of a modified electrode can be used to introduce new selectivity into a preparative reaction that is not observed in the absence of either the modified electrode surface or the effort to confine the reaction to that surface. The observed selectivity can be optimized in the same way that confinement is optimized on an array and is dependent on the nature of the functionalized surface.