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Vinylaziridines from vinyl epoxides

Iain Coldham,*a Alan J. Collisb and Roger J. Moulda

aDepartment of Chemistry, University of Exeter, Stocker Road, Exeter, UK EX4 4QD
bDepartment of Discovery Chemistry, Pfizer Central Research, Sandwich, Kent, UK CT13 9NJ


This paper reports a new method for the synthesis of aziridines containing an alkene group attached to the 2-position of the aziridine ring. 2-Vinylaziridines1 are crucial intermediates for a number of synthetic transformations. They have been used for the preparation of pyrrolizidine2 and amaryllidaceae3 alkaloids, isosteres as peptide mimetics4 and other biologically active compounds.5

We were interested in preparing N-unsubstituted-2-vinylaziridines, as substrates for our study of the aza-Wittig rearrangement (with concomitant ring expansion) to tetrahydropyridines.6 Deprotonation a to the nitrogen atom, exo to the aziridine ring, is followed by [2,3]-sigmatropic rearrangement to the tetrahydropyridine ring.

We know very few methods for the preparation of N-unsubstituted-2-vinylaziridines and would welcome feedback to Iain Coldham in this area.

One method that we explored for the preparation of the required vinylaziridines involved the simple two-step ring-opening of epoxides with azide, followed by ring-closure to the aziridine with triphenylphosphine.7 The extension of this reaction to the ring opening of vinylepoxides is reported here.

Synthesis of vinyl epoxides

A selection of vinyl epoxides were prepared from cinnamaldehyde, according to Scheme 1. Epoxidation of cinnamaldehyde was performed using hydrogen peroxide in aqueous sodium bicarbonate.8 The epoxy-aldehyde was converted, using Wittig olefination, to the required vinylepoxides. Four vinyl epoxides, 2a.9 2b, 2c10 and 2d11 with different substitution patterns around the alkene were prepared. The epoxide 2b was formed as a mixture of stereoisomers, favouring the Z-alkene in a ratio 5:2 (experimental and data). The epoxide 2c was isolated as, predominantly, the more stable E isomer (10:1).

Ring-opening of the vinyl epoxides

All four vinyl epoxides undergo smooth ring-opening with azide under standard conditions7 (NaN3, NH4Cl, MeOH, H2O, heat) as shown in Scheme 2. The expected b-azido-alcohols 3a-d and 4a-d are the major products, with no significant regioselectivity in the ring-opening step. Both the phenyl ring and the alkene group appear to have a similar influence on the electrophilicity of the epoxide. The mixture of regioisomeric b-azido-alcohols is not a problem, as both regioisomers can be taken on to the next stage.

In addition to the b-azido-alcohols 3a-d and 4a-d, the azido-alcohols 5 were isolated in all cases, except from vinyl epoxide 2c. The formation of 5a-b and 5d is interesting and could involve one (or both!) of two mechanisms.

Experimental conditions and data for azido-alcohols 3-5

Direct SN2' attack of the azide ion on to the vinyl epoxide would lead to the products 5. Alternatively, [3,3]-sigmatropic shift of 4 via an allylic azide rearrangement would give 5. The likely pathway followed is via the [3,3] pathway, as it is possible to isolate and separate all three azido-alcohols 3a, 4a and 5a and observe that the b-azido-alcohol 4a converts slowly at room temperature to the d-azido-alcohol 5a. The extent of this rearrangement is greatest when R=R'=H as this converts the monosubstituted alkene into a disubstituted alkene. No rearrangement to the d-azido-alcohol 5c was observed as this would take the double bond out of conjugation with the ester functionality.10

Ring-closure with triphenylphosphine - Synthesis of vinylaziridines

The mixture of regioisomeric b-azido-alcohols 3a-d and 4a-d can be ring-closed to the aziridines 6a-d using triphenylphosphine in acetonitrile (Scheme 3).

The b-azido-alcohols 3a and 4a were taken on immediately in order to avoid the [3,3]-allylic azide shift. This gave the vinylaziridine 6a in reasonable yield (experimental).

For the formation of the aziridine 6b, the mixture of azido-alcohols 3b, 4b and 5b were used, although treatment of 5b with Ph3P did not result in the formation of aziridine 6b. The ratio of alkene stereoisomers of vinylaziridine 6b had changed to 3:2 in favour of the E alkene (experimental). We suspect that this may be a result of the preferential allylic azide rearrangement of Z-4b.

The ring closure with b-azido-alcohol 3c and 4c had to be carried out at room temperature, otherwise the aziridine 6c was isolated in low yield (36%), together with the imine 7c (35%) (Scheme 4).10 We have found that heating aziridine 6c in MeCN results in the formation of 7c via an azo-methine ylide. This ylide can be trapped with dipolarophiles to give pyrrolidine product.10 The type of ring-opening that occurs with the aziridine 6c does not take place with the other vinylaziridines as it requires the electron-withdrawing ester group to stabilise the ylide.

The aziridine 6d was isolated in low yield and was unstable to purification. This is a result of the two methyl groups (R [1] and R [2]), which presumably activate the aziridine to electrophilic ring-opening (with build-up of positive charge stabilised by the two Me groups).


The well-known methodology for the conversion of epoxides to aziridines via azide opening, followed by closure with Ph3P has been shown to be successful on a selection of vinyl epoxides. This has allowed a short (three-steps from an epoxy-aldehyde) method for the preparation of vinylaziridines. The N-unsubstituted-2-vinylaziridine 6c is formed in 46% overall yield for the three steps from aldehyde 1. The overall yield is reduced for other vinylaziridines, due mostly to problems with allylic rearrangement of the azide group.

We have shown that such vinylaziridines can be functionalised further, by alkylation on the nitrogen atom of the vinylaziridine, as shown in Scheme 5. This sets the stage for the utilisation of these vinyl aziridines for further transformations in organic synthesis.


We thank the SERC for an Earmarked Studentship (R.J.M.) and Pfizer Central Research for a CASE Award (R.J.M.).


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