Another requirement of a catalyst that is to be used in organic synthesis is the ability to aziridinate many different substrates. In addition, the yields obtained may provide information as to the nature of the reactive species involved.
Much of the research into aziridination substrates has been directed towards the stereospecificity and regiospecificity of reactions. It has been reported by Evans that trans alkenes react stereospecifically to give trans aziridines, but c/s alkenes give varying ratios of the two possible aziridine products depending upon the catalyst used."^ However, Knight notes that in certain circumstances, small amounts of c/s aziridines can be obtained from trans dienes.^^"^
All of the aziridination reactions discussed in this and the following two sections were performed using the general aziridination procedure under standard conditions (see Section 4.5) unless otherwise stated.
Aziridination Of Alkenes After styrene, the second most studied substrate is cyclohexene, the former being an activated aikene and the latter being a deactivated aikene. Generally, cyclohexene gives lower yields of aziridine than styrene, but this effect is very much dependent upon the catalyst used. For instance, using [Tp*Cu(PPh3)] as catalyst, the yield of aziridine with
cyclohexene as substrate is 14%, 6 6% lower than the corresponding yield with
styrene. However, with [Tp*Cu(CO)] as catalyst, the yield of cyclohexene aziridine is 3%, 97% lower than the equivalent yield using styrene. A summary of the results obtained in these reactions is given in Table 3.8 below, with the yields given as a percentage. It can be seen that none of the three alternative alkenes give the high yields commonly obtained with styrene.
Catalyst
Yields (%)
Styrene Acrylonltrlle Cyclohexene Methyl Methacrylate
[Tp*Cu(PPh3)] 80 24 14 15 [Tp*Cu(CO)] 100 31 3 26 [CuTp*2] 5 3 [Cu(Et2dtc)U 78 39 [Cu(Et2dtc)2] 80 14 19 [Cu(Et2dtc)2}[FeCi4] 76 24 [Cu(Et2dtc)2]CI04 5 4 [(Ph3P)CuCI]4 90 60 29
Table 3.8 Yields of aziridinations of alkenes
Aziridination Of Dienes And Trienes The aziridination of several dienes was attempted in order to examine the regioselectivity of the aziridination reaction as well as the possibility of more than one aziridination taking place on one molecule of substrate. The substrates investigated included a bicyclic diene (bicyclo-[2.2.1]-1,5-heptadiene), a long-chain aliphatic diene (2,5-dimethylhexa- 1.5-diene), cycloheptatriene and the cyclic dienes 1,3-cyclooctadiene and 1.5-cyclooctadiene.
When 1,5-cyclooctadiene was added to Phl=NTos, a vigorous exothermic reaction took place, the only product identified being T0SNH2. The aziridination
of 1,5-cyclooctadiene was therefore performed according to the reverse procedure (see Section 4.6) using [Tp*Cu(C2H4)] / [Ip *C u]2 (1:1) as catalyst.
The NMR spectrum of the reaction mixture showed some small peaks between 3 ppm and 4 ppm, a region where aziridine ring proton signals are normally found. However, no product could be unambiguously identified and the mass spectrum showed no evidence of aziridination.
The reactions involving 1,3-cyclooctadiene, cycloheptatriene and
2,5-dimethylhexa-1,5-diene gave similar results, with the major product being T0SNH2 and the NMR spectra also showing small peaks that could possibly
be due to aziridine. No products other than T0SNH2 could be identified in any of
the reaction mixtures and the low yields obtained prevented isolation by column chromatography.
However, the aziridination of bicyclo-[2.2.1]-1,5-heptadiene gave a high yield of an unidentified product which, from evidence obtained from the mass spectrum, appeared to result in the reaction of the substrate with one equivalent of NTos. The major product was then isolated by column chromatography. A ^H NMR spectrum of the white solid thus obtained showed many peaks, including those of T0SNH2 and those of other, unidentified minor products. However, between
eight and ten resonances were identified as belonging to the major product of the aziridination reaction. The high number of individual resonances indicates low symmetry in the molecule, thus ruling out the presence of an aziridine. Other indications that the product is not an aziridine are the presence of a broad peak at 4.7 ppm assignable to an amino proton and the presence of four resonances in the olefinic region of the spectrum. Since the substrate initially had four olefinic protons, it would appear that neither aikene functionality has been reduced. Despite good data being available from both the ^H NMR and mass spectra, this product could not be identified (for details of the spectra see Section 4.8.2 and Appendix 2).
Aziridination Of Other Muitipiy-Bonded Substrates Many compounds similar in structure to aziridines have been synthesised and it is possible to envisage the formation of each of these derivatives from the reaction of a nitrene with a suitable substrate. Compounds such as 1-azirines and diaziridines have been known since the late 60’s and early 70’s, but 2-azirines have yet to be synthesised since they would have 4 Ti-electrons and would therefore be antiaromatic.^^®'^^° Triaziridines have only been known since the 80’s and are synthesised by the reaction of nitrene with azoisopropane followed by photolysis of the resulting azimine.^^^ Another interesting aziridine derivative is the 2,4-diazabicyclo[1.1.0]butane system which has two aziridine rings fused along the carbon-carbon bond.^^ These derivatives are all shown in Figure 3.1.1 below. R R R N N N
Z A
(a) (b) (c) R RN N / \ ? ,N — N , \ / R -N ^ '^ '^ N -RR
R
N
R (d) (e) (f)(a) 1-azirine (b) 2-azirine (c) diaziridine (d) triaziridine (e) 2,4-diazabicyclo[1.1.0]butane (f) azimine
Figure 3.1.2 Unusual aziridine derivatives
It can be envisaged that reaction between a nitrene and an azo compound could produce a triaziridine, although it is more likely that an azimine would be formed.
However, the NMR spectrum of a reaction between Phl=NTos and
azobenzene catalysed by [Cu(Et2dtc)2] only showed resonances for T0 SNH2 and
un reacted azobenzene. Reaction between a nitrene and an alkyne could possibly result either in the formation of a 2-azirine or, if two equivalents of
nitrene react, a 2,4-diazabicyclo[1.1.0]butane derivative. The formation of the two derivatives shown in Figure 3.1.2 can also be envisaged, although the latter reaction is unlikely since the product would have eight jr-electrons and would therefore be antiaromatic.
2 R - C ^ = C —R + TosN:
R N—Tos
2 R—C ~C—R + 2 TosN! --- ► Tos—N N—Tos
R R
Figure 3.1.3 Hypothetical products from reaction of alkyne with nitrene
Reaction of Phl=NTos with dimethyl acetylene dicarboxylate (DMAD) catalysed by [Cu(Et2dtc)2] showed no evidence of any transfer of nitrene in either the
NMR spectrum or the mass spectrum. However, a colour change from dark brown to yellow was observed during reaction of Phl=NTos with di-n-propyl acetylene catalysed by [Cu(Et2dtc)2]. In addition, the NMR spectrum showed
four peaks not attributable to the starting material and the mass spectrum gave some evidence for the reaction of the alkyne with a TosN species. Despite these promising indications that reaction had taken place, no product could be identified or characterised.
In summary, styrene is the substrate that consistently provides the highest yield of aziridine, although some catalyst-substrate combinations also give high yields. The aziridination of dienes was not successful, with low yields of unidentified products being obtained except when using bicyclo-[2.2.1]-1,5-heptadiene. Similarly, the aziridination of more unusual substrates generally gave poor results, although some interaction of nitrene with a non-activated alkyne was observed.