Reactions Using Different Nitrene Sources

Although Phl=NTos is by far the most widely used nitrene source in catalysed aziridination reactions, there exist several other methods of generating nitrenes. Perhaps the most common is the use of azides which, in the presence of a catalyst or when thermally or photolytically excited, decompose to yield N2 and a

nitrene. This was the method utilised by Kwart and Kahn in the first catalytic formation of aziridines from olefins."^ Evans has assessed the aziridination ability of four nitrene sources, chosen because of their ability to form imido complexes from molybdenum-oxo complexes.^ These potential nitrene sources are shown in Figure 3.1.4, the yields obtained by Evans being 96% for Phl=NTos and 12% for T0SN3, the remaining two being inactive."^

Me^

Ph

^ S = N T o s P h l= N T o s

© © / \© 0

T o s N ^ = N = N ^ N---NTos

Figure 3.1.4 Nitrene sources investigated by Evans

Since our studies with Phl=NTos had shown differences to the results of Evans, it was decided to assess two other nitrene sources from this group. Me2S=NTos

was readily prepared from Me2S and TosNCINa and was assessed using

[Cu(Et2dtc)2] as c a t a l y s t . N o colour change was observed and no peaks due

to aziridine were found in the NMR spectrum after standard work-up. TosNs was prepared by reaction of TosCI with NaNs and was assessed using [Tp*Cu(C2H4)] / [Tp*Cu]2 (1:1) as c a t a l y s t . T h e solution became pale yellow

during the reaction, and the NMR spectrum showed a 35% yield of aziridine. These two results appear to correlate well with those of Evans, suggesting that his assertions that N-1-pyridinium sulfonamidate is inactive and that Phl=NTos is the most active nitrene source are correct. However, the future development of new nitrene sources could lead to higher yields, greater selectivity and a wider range of aziridine products.

The molybdenum-imido complexes mentioned above are known to react with phosphines, causing a two-electron reduction along with formation of a phosphorus imine/^^ It is possible to envisage styrene acting as the reductant in an analogous reaction which forms aziridines. These complexes could thus possibly provide an alternative source of nitrene and therefore one example, [Mo(Et2dtc)2(Nteu)2] was assessed as such using [Tp*Cu(C2H4)] / [Tp*Cu]2 (1:1)

as catalyst. Upon reduction, the imido complex is known to undergo a colour change from orange to purple.^^® However, no such colour change was observed during the aziridination reaction and no aziridine was detected in the NMR spectrum. The reaction was left to stir for a further three days, but no colour change was observed. A solution of one equivalent of PPha in CH2CI2

was therefore added to the reaction mixture. PPha is known to abstract the imido group from molybdenum bis-imido complexes affording a molybdenum(IV) imido complex and Ph3P=NR.^^® The addition of PPhs had no effect on the

aziridination reaction, with no colour change taking place and no evidence of either aziridine or phosphorus imine being found in the NMR spectrum.

TosNCINa, utilised in the synthesis of Mo2S=NTos, is known to transfer the TosN

moiety to organic substrates in reactions involving ferrous chloride and therefore has the potential to act as a nitrene source in aziridination reactions. TosNCINa is supplied as a dihydrate and was assessed both in its hydrated and dehydrated forms using [Cu(Et2dtc)2] as catalyst. The yields obtained were 44%

and 45% respectively, highlighting the fact that the presence of water does not significantly affect aziridination reactions. The yields were slightly higher than half of those obtained with Phl=NTos, suggesting that TosNCINa is a good source of nitrene and is perhaps the second most effective nitrene source known. Indeed, using [Tp*Cu(PPh3)] as catalyst, 73% yield was obtained, only

7% lower than that obtained with Phl=NTos. However, a reaction using [(Ph3P)CuCI]4, the most efficient catalyst with Phl=NTos (see Section 3.1.3),

gave no aziridine at all. This suggests that the reaction mechanism functioning when TosNCINa is employed is somewhat different to that operating during aziridination reactions using Phl=NTos.

The fact that TosNCINa has been shown to act as a nitrene source in aziridination reactions allows the possibility of utilising a new generation of nitrene sources not based on the p-toluenesulfonyl group. The p-toluenesulfonyl group is rarely used as a nitrogen protecting group in organic synthesis due to the difficulty of its eventual r e m o v a l . O t h e r amide-based protecting groups such as the f-butyl carbamate (BOG) group shown in Figure 3.1.4 are much more widely used since they are much more easily removed. These type of carbamate protecting groups can easily be converted to N-sodio, N-chloroamine nitrene sources by a conproportionation reaction between the relevant amine and dichloroamine followed by reaction with NaOH. There is therefore the possibility of the development of a new class of nitrene sources that will allow tailoring of the properties of the protecting group on nitrogen, a development that would be highly attractive to synthetic organic chemists.

f-butyl carbamate (BOG)

G O O

O NH2 O NCI2 0 NHCI

R .

A

A

e

O NHCI O NCI

Figure 3.1.4 Synthesis of N-sodio, N-chloroamine nitrene sources

In summary, whilst it appears that Phl=NTos is the most effective nitrene source known, the activity of TosNCINa opens the possibility of a new generation of nitrene sources that are more attractive to the synthetic organic chemist. However, the yields obtained with TosNCINa do not correlate with those obtained with Phl=NTos, suggesting the existence of an alternative mechanism for nitrene formation.