Reactions of aziridines

Another interesting and synthetically useful behavior of aziridines is their tendency to open thermally to azomethine ylides, a process which can also be facilitated by Lewis acid catalysts. These reactive intermediates can be trapped by a variety of dipolarophiles to give new heterocyclic species. Methyl vinyl ethers convert aziridines such as 172 into a pyrrolidine derivative (i.e., 174) in the presence of a zinc(salen) Lewis acid catalyst 171 04JA2294 . Similarly, nitriles (e.g., 175) lead to the formation of 2,4-disubstituted 177-imidazolines (e.g., 176) under the catalysis of boron triethyloxonium tetrafluoroborate 04TL 1137 . Under almost 

In a similar vein, a resin-supported rhodium-complexed dendrimer 184 has been shown to promote the carbonylative ring expansion of aziridines to P-lactams, as illustrated by the conversion of the A -f-butyl aziridine 185 to the corresponding lactam 186 in almost quantitative yield. The supported catalyst, which shows reactivity comparable to the solution-phase variety, is easily recovered by filtration and exhibits no significant loss of activity upon recycling. 

04ACR645 D. V. Deubel, G. Frenking, P. Gisdakis, W. A. Herrmann, N. Rosoh, J. Sundermeyer, Acc. Chem. 

04AGE84 M. Bandini, P. G. Cozzi, P. Melchiorre, A. Umani-Ronohi, Angew. Chem. Int. Ed. 2004, 43, 84. 

04CC554 S. Bhattachaijee, J. A. Anderson, J. Chem. Soc., Chem. Commun. 2004, 554. 

Thioacetic acid-mediated nucleophilic ring-opening of various aziridines was described as a key step in the synthesis of structurally diverse taurines 07JOC4543 . Ring-opened products were subsequently oxidized with performic acid and hydrolyzed in hydrochloric acid to provide 2-substituted, 2,2-disubstituted, and 1,2-, 2,2-, and 2,V-alkylene taurines. 

Nitrogen-based nucleophiles continue to remain popular in ring-opening reactions of aziridines. a-Substituted-a-methoxycarbonyl-V-nosylaziridines were opened with a variety of functionalized amines to provide access to enantiopure a,a -disubstituted (3-lactam scaffolds for ditopic peptidomimetics 07OL101 . A related intramolecular regioselective 3,Y-aziridine ring opening with an a-amino functionality was reported in the synthesis of 

A regioselective ring-opening reaction of A-tosylaziridincs with anilines followed by lactamization to form products such as 55 was reported 07TL2007 . Intramolecular lactonization to 3-arylidenelactone 56 was observed when the reaction was carried out in the 

A novel Pd-catalyzed asymmetric annulation was reported between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines 07OL2357 . The resulting pyrrolopiperazinones such as 58 served as key intermediates in the enantioselective synthesis of longamide B and a number of other pyrrole alkaloids. 

New asymmetric polymetallic catalysts were reported for the ring-opening reaction of ffieso-aziridines with TMSCN 07T5820 . Three contiguous tertiary stereocenters were generated via the reaction of active methylene nucleophiles with tosylated aziridines under mild phase-transfer catalyzed conditions. For example, reaction of aziridine 61 with the anion derived from 62 provided substituted cyclopentane 63 in excellent yield 07OL4677 . 

Typically, the stereospecific formation of quaternary centers is as problematic as selective nucleophilic attack at the more substituted carbon of aziridines. Interestingly, a copper mediated methodology has been reported that does both 060L5105 . Although N-tosyl aziridines show favorable results, A-nosyl aziridines gave the best results. The reaction of 89 with a variety of phenols yielded 90 in moderate yields. 

Another problem with the reaction of phenols with aziridines is the selectivity between O-alkylation vs C-alkylation. A recent report has identified that the use of (ArO)3B selects for C-alkylation 06OL2627 . Most of the examples reported in this paper showed less than 5% of the O-alkylation product. What is interesting about this report is the stereochemistry of the product. While the mechanism is not known, the product is formally an SNl type product. Generally less than 5% was the product of inversion of configuration (the Sn2 product). In addition to the A-tosyl, both the A-Cbz and A-Dpp aziridines gave excellent yields of aziridine-opened product. 

Typically in ring-opening reactions of aziridines, the amine functional group is retained in the product molecule. An example of such a reaction where the amine group has been lost has recently been reported 06TL977 . An intramolecular Friedel-Craft reaction of aziridine 91 leads to the expected product as an intermediate. Under the rather drastic reaction conditions, the sulfonamide is lost leading to formation of the naphthalene ring. 

A novel C-3 functionalization of methylene aziridines has also been reported 06T8447 . Selective deprotonation of 98 to form 99 and the reaction 99 with an electrophile yielded 100 in good yields. In this way, a variety of alkyl groups could be selectively placed on the aziridine. These researchers also found that (S)-a-methylbenzyl substituted methylene aziridines, 101, when deprotonated and reacted with a variety of electrophiles gave 102 in moderate yields and with good diastereoselectivity. 

F3CT C02Et Solvent (temp.) Lewis acid Yield LLJ CM o o o CO LL 

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The first involves the reaction of aziridine with an aldehyde or a ketone and the treatment of the resulting carbinol with hydrogen selenide (Scheme 69) (Methode I). 

Reaction with Sulfur Nucleophiles, Because sulfai is highly nucleophilic, reactions of aziridines with sulfur nucleophiles generally proceed rapidly (111) and with good yields. The reaction of hydrogen sulfide [7783-06S-J with ethyleneimine yields cysteamine [60-23-1] (2-mercaptoethylamine) or bis(2-aminoethyl)sulfide [871-76-1] (2,112) depending on the molar ratio of the reactants. The use of NaHS for the synthesis of cysteamine has also been described (113). 

The reaction of aziridines (R = H, triazinyl) with thiosulfate yields i -aLkyl thiosulfates (131,132), which are known as Bunte salts (133). 

Cyclic Carhene Complexes. The reaction of aziridines with carbonyl, thiocarbonyl, or isonitrile ligands in Mn, Re, Fe, Ru, Pd, or Pt complexes leads to formation of cycHc carhene complexes (324—331). 

Cycloaddition reactions of aziridines with a wide assortment of dipolarophiles have been studied. The reaction of dialkyl azodicarboxylates with the cf5-aziridine (27) is stereospecific... 

Reaction of aziridine peptides 139 (Scheme 3.50) and dibenzylphosphoric acid... 

Cycloaddition reactions of aziridine-2-carboxylic esters have also been used... 

The ring-opening reactions of aziridines 16 with amines deserve special attention. Unlike ring-openings with the other nucleophiles examined, they do not require added base, and they do not produce stoichiometric byproducts (as with azide). In certain cases, they do not even require a solvent, as exemplified by the ring-opening of aziridine 18 (Table 12.12, entries 1-3). In addition, the reactions... 

The majority of reactions of aziridines deal with acid-catalyzed ring opening with various nucleophiles. In this review only reactions with aziridine-2-car-boxylic esters are summarized (for other types of aziridines, see ref. [3]). 

Reductive ring-opening reaction of aziridine ester constitutes a convenient access to amino acids a typical example is given in Scheme 27 [37]. 

These ligands can readily be obtained by a Grignard reaction of aziridine esters, followed by an acidic detritylation (see Scheme 40) [19,55]. These aziridine carbinol-derived catalysts are equally efficient as the Corey ligand 55 derived from proline carbinols (Fig. 4) [55,56]. 

It has been found that A-tosyl aziridines undergo oxidative addition to palladium complexes to form azapalladacyclobutanes <06JA15415>. Reaction of aziridine 95 with Pd2(dba)3 and 1,10-phenanthroline provides the palladacycle 96 in 45% isolated yield. This compound is an air stable solid. Treatment the palladacycle 96 with catalytic Cul is believed to open the palladacycle to form a copper intermediate, which cyclizes to cyclopentyl alkylpalladium intermediate 97. Loss of Cul then provides the product palladacycle 97 as an air stable solid. Several different aziridines were examined in this reaction. Only a limited set of olefin substituted aziridines provided the azapalladacyclobutanes (e.g. 96). 

Figure 15.7 The reaction of aziridine derivatives with fullerenes also can give pyrrolidine derivatives useful for...

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