Synlett 2006(19): 3205-3217  
DOI: 10.1055/s-2006-951566
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

Methyleneaziridines: Unusual Vehicles for Organic Synthesis

Michael Shipman*
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK
Fax: +44(2476)524112; e-Mail: m.shipman@warwick.ac.uk;
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Publikationsverlauf

Received 20 March 2006
Publikationsdatum:
23. November 2006 (online)

Abstract

This account describes the development of methylene­aziridines as heterocyclic building blocks for a variety of useful synthetic transformations including multicomponent reactions, ­cycloadditions and radical cascades.

1 Introduction

2 Preparation of Methyleneaziridines

2.1 Ring Closure to Methyleneaziridines

2.2 Functionalization of Methyleneaziridines

3 Multicomponent Reactions

3.1 Ketone-Forming MCRs

3.2 Amine- and Heterocycle-Forming MCRs

3.3 α-Amino Nitrile Forming MCRs

4 [4+3] Cycloadditions

5 Radical Rearrangements

6 Conclusions

13

Purification by distillation is preferred over chromatography. Poor mass recovery is observed when methyleneaziridines are subjected to this purification technique. Exceptions include derivatives bearing substituents on the exocyclic double bond wherein high mass recovery and purity can be achieved by chromatography on silica gel pretreated with Et3N.

23

Margathe, J. F.; Shipman, M.; Smith, S. C. unpublished results.

30

It is unclear why Bottini and Olsen (ref. 29) were unable to detect exchange with the solvent under their experimental conditions. However, we suspect that an insufficient amount of base was added. This conclusion was reached on the basis of the following observations. First, for the exchange experiment, they used just a catalytic quantity (0.26 equiv) of commercial sodium amide, whereas cyclisations were conducted using NaNH2 made in situ from sodium metal and FeCl3. In our experience, the activity of commercial material is inferior and often necessitates the use of a large excess of reagent. Second, 28 used in the experiment was contaminated with 7% of the corresponding alkyne which would have consumed a significant proportion of the added base.

46

This process involves the reaction of two reagents together to form an intermediate that is captured by the subsequent addition of further reagents. Hence it is more precisely defined as a sequential component reaction.

70

As far as we are aware, the toxicological effects of methyleneaziridines are unknown. However, since the adverse health effects of aziridines are well established, it is prudent to exercise caution in the handling of methyleneaziridines. Avoid all skin contact and perform all manipulations in a well-vented fume cupboard with adequate personal protection measures.