Copper-Mediated Single-Electron Approach to Indoline Amination: Scope, Mechanism, and Total Synthesis of Asperazine A.

Pyrroloindolines bearing a C3-N linkage comprise the core of many biologically active natural products, but many methods toward their synthesis are limited by the sterics or electronics of the product. We report a single electron-based approach for the synthesis of this scaffold and demonstrate high-yielding aminations, regardless of electronic or steric demands. The transformation uses copper wire and isopropanol to promote the reaction. The broad synthetic utility of this heterogeneous copper-catalyzed approach to access pyrroloindolines, diketopiperazine, furoindoline, and (+)-asperazine is included, along with experiments to provide insight into the mechanism of this new process.

ß-Silyloxy Allylboronate Esters through an Aldehyde Borylation/Homologation Sequence.

The areas of carbonyl borylation and the homologation of carbon-boron bonds have provided a number of fruitful methods in organic synthesis. Combining these approaches, the homologation of α-oxyboronate esters, provides pathways to access complex organoboronate esters stereoselectively. To this end, the homologation of α-silyloxyboronate esters with lithiated allyl chlorides to form ß-silyloxy allylboronate esters is reported. Direct oxidation of the homologation products provides ß-silyloxy allyl alcohols in good yield. The homologation provides a range of allylic alcohols, albeit with low diastereoselectivity.

Asymmetric Electrophilic α-Amination of Silyl Enol Ether Derivatives via the Nitrosocarbonyl Hetero-ene Reaction.

The first example of a general asymmetric nitrosocarbonyl hetero-ene reaction is described. The procedure uses a copper-catalyzed aerobic oxidation of a commercially available chiral nitrosocarbonyl precursor (EleNOr) and is operationally simple. The transformation is both high yielding and highly diastereoselective for a range of silyl enol ether derivatives. A variety of synthetically useful postfunctionalization reactions are presented along with a mechanistic rationale that can be used as a predictive model for future asymmetric reactions with nitrosocarbonyl intermediates.

Nitrosocarbonyl Hetero-Diels-Alder Cycloaddition: A New Tool for Conjugation.

It is demonstrated that nitrosocarbonyl hetero-Diels-Alder chemistry is an efficient and versatile reaction that can be applied in macromolecular synthesis. Polyethylene glycol functionalized with a hydroxamic acid moiety undergoes facile coupling with cyclopentadiene-terminated polystyrene, through a copper-catalyzed as well as thermal hetero-Diels-Alder reaction. The mild and orthogonal methods used to carry out this reaction make it an attractive method for the synthesis of block copolymers. The resulting block copolymers were analyzed and characterized using GPC and NMR. The product materials could be subjected to thermal retro [4 + 2] cycloaddition, allowing for the liberation of the individual polymer chains and subsequent recycling of the diene-terminated polymers.