Wenker synthesis

The procedure reported here, which is that of Hassner and Heathcock,3 is more convenient than the Wenker synthesis of aziridines4 and appears to be more general.5 It represents a simple route from olefins to aziridines (via 8-iodo carbamates).356 Aziridines are also useful as intermediates in the synthesis of amino alcohols and heterocyclic systems.5,7-9... 

A. The Oalrid and. Wenker Reactions The preparation of an aziridino derivative is most frequently accomplished in a two-step synthesis from a suitably substituted 0-aminn alcohol. When the reaction is carried out via the /MialGabriel synthesis (Eq. 1). in honor of the discoverer of the prototype reaction. A convenient modification of this sequence, called the Wenker synthesis (Eq, 2), was published in 1936" and almost simultaneously reported independently in the patent literature."4- SR This involves the conversion of the amino alcohol into tb 0-amino hydrogen auifete (which undoubtedly exists as the zwitterion)... 

The literature should ho consulted for various modifications in the technique of the Wenker synthesis. S3< as-298 B 3M... 

The Wenker synthesis is not stereospecifio when the hydroxyl group of the amino alcohol is on benayhtypo carbon atom. t-Ephr-drine erythro) (XIX) and i -ephedrine (XVUla) give the... 

Graham reaction—additive oxidation Hoch-Campbell aziridine synthesis Payne rearrangement Wenker synthesis Aziridine synthesis... 

Wenker synthesis is a typical method for synthesis of aziridines in which 2-amino alcohols from natural or synthetic amino acids are cyclized by base. The synthesis of N-tosylaziridines 7 was accomplished by base-mediated cyclization of bis-tosylafes 6 of 2-amino alcohols 5 in water and dichloromethane in equal amounts (Scheme 1). The products were obtained in reasonable yields [23]. In a further improved procedure, the 2-amino alcohols are first converted into their hydrogen sulfates using chlorosulfonic acid and then cyclized by aqueous sodium hydroxide or sodium carbonate to corresponding aziridines (Scheme 2) [24],... 

The Wenker aziridine synthesis entails the treatment of a P-amino alcohol 1 with sulfuric acid to give P-aminoethyl sulfate ester 2 which is subsequently treated with base to afford aziridine 3. Before the discovery of the Mitsunobu reaction, wbicb transforms an amino alcohol into an aziridine in one step under very mild conditions, the Wenker reaction was one of the most convenient methods for aziridine synthesis. However, due to the involvement of strong acid and then strong base, its utility has been limited to substrates without labile functionalities. 

The mechanism for the Wenker aziridine synthesis is very straightforward. As depicted by conversion 2—>3, the transformation is a simple case of intramolecular Sn2 displacement process, in which the sulfate ester is the leaving group. 

As described in Section 1.7.1, the utility of the Wenker reaction is limited to substrates without labile functionalities because of the involvement of strong acid and then strong base. The Fanta group prepared a variety of aziridines by taking advantage of the Wenker reaction.For example, 6-aza-bicyclo[3.1.0]hexane (14) was produced from the ring-closure of ( )-rra s-2-aminocyclopentanol hydrochloride (13). In a similar fashion, sulfate ester 16 was prepared from A-methyl dl-trans- >-ssmnoA-hydroxytetrahydrofuran (15). Subsequent treatment of sulfate ester 16 with NaOH then delivered aziridine I . " Additional examples of Wenker aziridine synthesis may also be found in references 15-17. 

Water-solubilization 16, 501 Wenker aziridine ring synthesis 17, 537 Wessely-Moser rearrangement... 

Ethylenimines from 2-aminoalcohols via 2-aminosulfuric acid monoesters Wenker aziridine ring synthesis... 

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