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

2′-C-Methyluridine phosphoramidite: a new building block for the preparation of RNA analogues carrying the 2′-hydroxyl group

Surgical reduction: N-Heterocyclic carbene-borane complexes such as depicted are neutral, organic soluble analogues of borohydride anions with a weak hydridic character, compatible with organometallic catalysis. They are applicable for surgical reductions in complex, multifunctional molecules. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ionic and organometallic reductions with N-heterocyclic carbene boranes.

Publisher Summary This chapter focuses on important developments dealing with quaternization of annular nitrogen atoms of heterocyclic compounds The chapter is essentially divided into two main parts The first part describes the main electronic and steric factors of heteroaromatic nucleophilic reactants that influence their reactivity The second part provides references to recent important developments The chapter considers six-membered heteroaromatic rings before five-membered ones as the six-membered rings are studied in greater detail and consequently their reactions are better understood The chapter notes that quaternization of an annular nitrogen atom is carried out with a wide range of alkylating agents Most quaternization reactions involving an annular nitrogen atom and an alkylating agent proceed by way of an S N 2 reaction in which the inversion of configuration of a chiral reagent takes place One novel method, which indicates that the transition state is early, involves the study of volume changes Many approaches are made to obtain information about the nature of the transition state of quaternization reactions, including a study of kinetic isotope effects

Quaternization of Heteroaromatic Compounds: Quantitative Aspects

Nucleophilic borohydride: selective reductive displacement of halides, sulfonate esters, tertiary amines, and N,N-disulfonimides with borohydride reagents in polar aprotic solvents

Frank J. Dux

Papers

Nucleophilic borohydride: selective reductive displacement of halides, sulfonate esters, tertiary amines, and N,N-disulfonimides with borohydride reagents in polar aprotic solvents

Selective demethylation of quaternary salts with lithium propylmercaptide in hexamethylphosphoramide

1-tert-butyl-1,3-propanediol