Synthesis of Monocyclic Aziridines

There are a number of limitations associated with the synthesis of fused-ring aziridines that are not observed in the synthesis of monocyclic aziridines. As a consequence of this, some methods that work well for monocyclic aziridines and azirines have not been reported for fused-ring derivatives. 

Carbenes have also been used for the synthesis of monocyclic aziridines. The use of carbenes to prepare fused-ring aziridines has been much more limited. The reaction of dihydroquinoline 136 with dichlorocarbene provides a reasonable yield of the fused-ring aziridine 137 <19978677, 20030BC4040> (Equation 33). 

We have presented in this chapter a selection of the chemistry of fused-ring aziridines and fused-ring azirines. As expected this chemistry, to some extent, parallels that of monocyclic aziridines and azirines. Many of the syntheses of aziridines work equally well for both monocyclic and type I fused-ring aziridines. There are however a number of significant differences. For example, methods for the synthesis of type II aziridines are often not viable routes to... 

Monocyclic aziridines and 2//-azirines have found broad application in the synthesis of complex natural products. The facility with which these small ring nitrogen-containing compounds can be converted to important pharmaceutical products under mild conditions with wide functional group compatibility makes these molecules quite useful for heterocyclic chemistry. 

The formation of bonds c and b can take a couple of forms, either a Darzens-type approach (i.e., addition of a nucleophile bearing a leaving group) or addition of a carbene. Both of these routes have been used in the synthesis of fused-ring aziridines as well as monocyclic aziridines. The addition of a carbene or nucleophile such as an ylide to an imine can provide a nice route to fused-ring aziridines. The necessary cyclic imines are sometimes more readily obtained and used than the acyclic imines. These methods have largely been used on pyridine and quinoline derivatives. 

As with the mitomycins, general routes to the synthesis of FR900482 and analogs have evolved. A very straightforward approach is the formation of the aziridine ring late in the synthesis using an intramolecular N-alkylation. A second is the incorporation of an intact monocyclic aziridine as part of the formation of the tricyclic ring system. 

There are two general routes toward the synthesis of azinomycin. Both approaches generally prepare the top half of the molecule and then generate the reactive aziridine ring late in the synthesis. The two general approaches to aziridine formation are the formation of the exocyclic C-N bond through a nucleophilic displacement or an intramolecular conjugate addition/elimination of an intact monocyclic aziridine. 

Tetrahydropyrrolizines (210) and (211) can be formed via radical scission of either bond a or b in the intermediate vinyl-aziridine (208) but yields are moderate at best and the major product is the monocyclic pyrroline (209), formed by a 1,5-homo-dienyl rearrangement. The route therefore could provide a useful access to the pyrrolizidine framework if conditions could be identified which would allow more controlled and efficient breakdown of (208). The synthesis of substitute pyrrolines by ring expansion of vinyl aziridine derivatives has also been accomplished in a palladium-catalysed reaction. N -Tosyl-2-vinyl five- and six-membered nitrogen heterocycles (213) ace obtained in generally high yields under mild conditions from precursor dienyl nitrogen heterocycles (212) in the presence of a catalytic amount of [Pd(PPh ) ]. The complete diene unit is required for the... 

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