Nucleophiles opening aziridines

An indirect nucleophilic opening is depicted in Scheme 24. The functionalized vinyl aziridine 37 undergoes a Michael-initiated ring closure (MIRC) reaction upon treatment with suitable nucleophiles to give cyclopropanes with concomitant opening of the aziridine ring [34]. 

Aziridines may be prepared by the intramolecular nucleophilic opening of epoxides by amines and their derivatives (84CAR(130)103,92T5639,92TL487,92TL5351) (Scheme 15). 

Half this review is concerned with aziridination, but other cycloadditions are generally excluded, being reviewed elsewhere in this series (Volume 4, Part 4 and Volume 5, Part 4). The second half of this review covers additions of nitrogen and a chalcogen or halogen, or a second nitrogen. No examples of addition of N + P were found this transformation can be achieved indirectly by opening aziridines with phosphorus nucleophiles. ... 

Type I aziridines can be prepared via photolysis of functionalized pyridinium ions. Mariano and co-workers have shown that irradiation of pyridinium ion 40 via a 450 W Hanovia lamp with Vycor filter will induce a ring contraction to produce a fused-bicyclic aziridine moiety 41 (Equation 16) <1996JOC4439>. The azabicyclo[3.1.0]hexane prepared through this method can rapidly experience nucleophilic opening to produce an amine-substituted cyclo-pentene. 

Nitriles can act as nitrogen nucleophiles in aziridine ring-opening reactions. Two examples are shown in Scheme 25 in which a formal [3-1-2] cycloadduct is the final product. Tosylaziridine 147 was reacted with benzoni-trile and BF3 OEt2 catalysis to produce the r-fused imidazoline 148 <2004TL1137>. The utility of the reaction is limited in the case of cyclic aziridines to benzofused aziridines and either aryl or benzyl nitriles. It was also found that the reaction required stoichiometric BF3. Lesser amounts of Lewis acid reduced the chemical yield drastically. 

The opening of halocyclopropanes to allyl systems according to equation 124 can happen thermally or with the assistance of electrophiles and nucleophiles . Some recent examples include an efficient cyclopentenone synthesis (equation 125) ", an electrocyclic opening/cyclization sequence giving functionalized furan and pyran derivatives (equation 126), an elegant total synthesis of the very fast death factor alkaloid ( ) anatoxin and a nice application of the well known nucleophilic opening to the preparation of crystalline methylene aziridines (equation 127) . 

Intramolecular 1,3-dipolar cycloaddition of azide (81) proceeds through a triazoline and vinyl-aziridine (82) and results in the formation of tetrahydropyrrolizidine (83) and (84). This represents a formal total synthesis of supinidine. Thermolysis of vinyl aziridine (82) leads to pyrrolizidine (84) probably via azomethine ylides, while the nucleophilic opening leads exclusively to (83) through an intermediate allylic iodide (85). The latter is produced as a mixture of (E) and (Z) isomers but is converted to (83) via an equilibrium and recyclization of the (Z)-isomer (Scheme 30) <85TL3523, 85TL3527). 

The nucleophilic opening of aziridines has also proved useful in peptide synthesis. A number of A-tosyl-aziridines (253 R = H, Me, Pr, or Ph) were opened with phenol or phenate ion in an attempt to introduce the /8-phenoxy-group to amino-acids, such groupings being known to be present in cyclopeptide alkaloids. In the case of (253 R = Ph) the ring was regioselectively cleaved to (254) (100%). 

In this section, we discuss a few early examples from our laboratory, where water proved to be the optimal medium in a variety of processes. Nucleophilic opening of three-membered rings such as epoxides, aziridines, and episulfides are excellent click reactions because competing elimination processes are stereo electronically disfavored. As a result, high yields of ring-opened products are obtained. We have used the nucleophilic opening of epoxides... 

The facility with which oxiranes may be prepared and the ease with which they undergo ring opening with nucleophiles or electrophiles makes them useful synthons. Aziridines and especially thiiranes have been less widely exploited in this respect. 

Certain bifunctional nucleophiles allow cyclization after ring opening. The formation of 2-thiazolium salts (71JHC40S) and the analogous production of 2-amino-2-thiazolines (191) from aziridines and thiocyanic acid fall into this category (72JOC4401). 

Substituted 2-haloaziridines are also known to undergo a number of reactions without ring opening. For example, displacement of chlorine in (264) with various nucleophilic reagents has been found to occur with overall inversion of stereochemistry about the aziridine ring (65JA4538). The displacements followed first order kinetics and faster rates were noted for (264 R = Me) than for (264 R = H). The observed inversion was ascribed to either ion pairing and/or stereoselectivity. 

---