There are basically two kinds of hetero atoms in organic molecules: one kind confers electrophilic character upon the carbon atom to which it is bound, and the other kind turns it into a nucleophilic site. The development of methods permitting transitions between the two resulting categories of reagents has become an important task of modern organic synthesis. The scope of such umpolung of the reactivity of functional groups is discussed for the case of amines as an example. A method of preparing masked α-secondary amino carbanions consists in nitrosation of the secondary amine, followed by metalation of the resulting nitrosamine α-to the nitrogen, reaction with electrophiles, and subsequent denitrosation. Many examples are given for each of these steps which illustrate the wide scope of the overall synthetic operation (electrophilic substitution at the α-C atom of the secondary amine). Preliminary applications and a method for avoiding the handling of nitrosamines are presented, and the report concludes with a brief account of the significance of nitrosamines in the study of carcinogenesis and mutagenesis.

Umpolung of Amine Reactivity. Nucleophilic α-(Secondary Amino)-alkylation via Metalated Nitrosamines†‡

Es gibt prinzipiell zwei Arten von Heteroatomen in organischen Molekulen: Die einen machen das mit ihnen verbundene Kohlenstoffatom zu einem elektrophilen, die anderen zu einem nucleophilen Zentrum. Die Entwicklung von Methoden zum Uberwechseln zwischen den beiden darauf beruhenden Kategorien von Reagentien ist eine wichtige Aufgabe der modernen organischen Synthese. Moglichkeiten dieser Umpolung der Reaktivitat funktioneller Gruppen werden am Beispiel der Amine diskutiert. Eine Methode zur Herstellung von maskierten α-sek.-Aminocarbanionen besteht darin, das man das sekundare Amin nitrosiert, das entstandene Nitrosamin in α-Stellung zum Stickstoff metalliert, mit Elektrophilen umsetzt und entnitrosiert. Fur jeden dieser Schritte wird eine Anzahl von Beispielen gegeben, die die grose Anwendungsbreite der synthetischen Gesamtoperation (elektrophile Substitution am α-C-Atom des sekundaren Amins) belegen. Erste Anwendungen und ein Verfahren zur Umgehung des Hantierens von Nitrosaminen werden vorgestellt, und zum Schlus wird die Bedeutung der Nitrosamine fur die Carcinogenese- und Mutageneseforschung kurz erortert.

Umpolung der Reaktivität von Aminen. Nucleophile α‐sek.‐Aminoalkylierung über metallierte Nitrosamine

Rearrangements in organomagnesium chemistry

To date, more than 100 congeners of the akuammiline alkaloid family have been isolated. Their signature structural element is a methanoquinolizidine moiety, a cage-like scaffold structurally related to adamantane. The structural variations of the family members originate from oxidative processes that mostly trigger rearrangements of the methanoquinolizidine motif. The family of the akuammiline alkaloids is best represented by strictamine. It bears the least functionalized carbon skeleton of all family members without lacking the signature structural motifs. Herein, we report the formal synthesis of strictamine through a Stevens [2,3]-sigmatropic rearrangement as a key step and the synthetic pitfalls related with its synthesis.

Formal Total Synthesis of (±)-Strictamine by [2,3]-Sigmatropic Stevens Rearrangements.

Rearrangement of carbanions and of ylides derived from 4-thiacyclohexenyl systems

Two representative cases of the [2, 3] sigmatropic rearrangement are described, and the mechanism of this reaction is discussed.

V. Rautenstrauch

Papers

Sigmatropic Reactions in Carbanions. II†. The Rearrangement of Allylic Ammonium Ylides