No abstract

Inductive heating has emerged as a new heating technique in the laboratory, particularly when combined with miniaturized flow reactor devices. Traditionally, inductive heating is found in industrial applications like the heating of large metallic objects such as in the bending of pipes, bonding and welding. New fields of application are the preparation of nanotubes as well as hyperthermia in the treatment of cancer. This account specifically addresses the use of heatable materials such as superparamagnetic iron oxide nanoparticles in many areas of organic synthesis and how this enabling technology compares to conventional as well as microwave heating.

SummaryThe multistep flow synthesis of vinyl azides and their application in the synthesis of vinyltriazoles is reported. The synthesis relies on a stable polymer-bound equivalent of iodine azide that serves to carry out 1,2-functionalization of alkenes in a telescope flow protocol. The intermediate 2-iodo azides are subjected to a DBU-mediated polymer-supported elimination step yielding vinyl azides in good yield. The third step involves the formation of vinyl triazoles by a copper-catalyzed Huisgen-"click" cycloaddition. The required heat is generated by electromagnetic induction based on copper. Copper serves both as heatable as well as catalytically active packed-bed material inside the flow reactor.

We report the palladium-catalyzed asymmetric allylic alkylation (AAA) reaction of a variety of nitrogen-containing aromatic heterocycles, including pyrazine, pyrimidine, pyridazine, quinoxaline, and benzoimidazole derivatives. The mesityl ester, whose steric bulk prevents competitive deacylation of the electrophile from "hard" nucleophiles, is introduced as a new leaving group in allylic alkylation chemistry. In contrast to our previous studies of AAA reactions with pyridine-based substrates, no precomplexation with a Lewis acid is required before deprotonation with LiHMDS, underscoring the relative acidity of these electron-deficient nucleophiles.

A new reactivity pattern and extended reaction scope has been obtained by transferring a reaction from batch mode to flow.

A continuous flow protocol for the oxidation of allylic and benzylic alcohols to aldehydes and ketones, respectively, using oxygen gas or atmospheric air is reported. The key features of this work are gold nanoparticles that are attached to the surface of nanostructured core shell particles composed of an Fe 3 O 4 -containing core and a silica shell. These nanostructured particles exert superparamagnetic properties and thus inductively heat up in an external oscillating electromagnetic field, conditions under which the gold catalyst is able to perform these oxidation reactions.

A combination of mutasynthesis, precursor-directed biosynthesis and semisynthesis provides access to new ansamitocin derivatives including new nanostructured particle-drug conjugates. These conjugates are based on the toxin ansamitocin and superparamagnetic iron oxide-silica core shell particles. New ansamitocin derivatives that are functionalized either with alkynyl- or azido groups in the ester side chain at C-3 are attached to nanostructured iron oxide core-silica shell particles. Upon exposure to an oscillating electromagnetic field these conjugates heat up and the ansamitocin derivatives are released by a retro-Diels-Alder reaction. For example, one ansamitocin derivative exerts strong antiproliferative activity against various cancer cell lines in the lower nanomolar range while the corresponding nanostructured particle-drug conjugate is not toxic. Therefore, these new conjugates can serve as dormant toxins that can be employed simultaneously in hyperthermia and chemotherapy when external inductive heating is applied.

Heiße Chemie! Induktives Heizen unter Hochfrequenzbedingungen und Durchflusschemie sind eine ideale Kombination für Hochtemperatursynthesen. Dies konnte in der kontinuierlichen Mehrstufensynthese des Neuroleptikums Olanzapin (Zyprexa) gezeigt werden. Sie umfasst drei Reaktionen mit induktivem Heizen und zwei kontinuierlich betriebene Reinigungsoperationen.