Acyl aziridines

The reaction of R COCH CHR (R = Ph or Me, R = Ph or COPh) with (-l-)-(225) in MeOH gave chiral 2-acyl-aziridines (226). Thus trans-l-benzoy -2-phenylethene, after reaction with (-l-)-(225) in MeOH at room temperature for 6days,gave(-)-(2R,3i )-rran.9-(226 R = R = Ph) (55%) with 30.4% optical yield. 

Conjugate addition of O-alkylhydroxylamines to a,P-unsaturated ketones was effectively catalyzed by an isolable complex of scandium with a chiral phosphate ligand (Sc[(R)-BNP]3) [124]. The corresponding P-amino ketones were generated in almost quantitative yields with high enantioselectivities (Scheme 12.48). These products could be quantitatively converted into the 2-acyl aziridines upon treatment with a base catalyst without losing their enantiopurities. 

More examples of dual-functionalized reagents inclnde the reaction of 2-acyl-aziridines 93 with azides and alkynes. In this case, a three-component synthesis of 2-imino-5-arylidene-3-pyrrolines 94 was achieved snccessfnlly (Scheme 5.61) [61]. 

Stamm, H. and Gerster, G., Reactions with aziridines. XXI. The (Michaelis-) Arbuzov reaction with N-acyl aziridines and other amidoethylations at phosphorus, Tetrahedron Lett., 1623, 1980. 

C, and then three molecular equivalents of acetyl chloride and triethy-lamine were added. Three types of acetylated materials, 11, 12, and 13, were isolated accompanied by a small amount of thioketone 7 and thioamide 9 (Scheme 8 and Table 6). All of the acetylated materials showed optical activity. For the reaction of 6a, 84% ee of 2-(acetylthio)aziridine 11a, 50% ee of 4-(acetyl-thio)oxazoline 12a, and 20% ee of 4-(acetylthio)oxazolidin-2-one 13a were obtained in 39,10, and 16% yields, respectively. In the reaction of 6b,c, the corresponding optically active materials 11-13 were obtained as shown in Table 9. The formation of oxazoline 12 involves the rearrangement ofAT-acyl aziridines, which occurs by intramolecular attack of the carbonyl oxygen at the ring carbon to cause rupture of the system. 

In the presence of a base, acid chlorides react readily with aziridines to give acylated aziridines (2,22,160—163). In the absence of a base, however, ring opening takes place and 2-chloroethylamides are obtained (2,164). Under suitable conditions acylated trialkylammonium salts of ethylenediamine can be prepared from acid chlorides, ethyleneimine, and tertiary amines (71). Acylated aziridines can be rearranged to 2-oxazolines by the action of heat, nucleophiles, or acids. The rearrangement of thioacylaziridines proceeds analogously (7,8,165—171). 

Reaction with Further Electrophiles of Group IVA (Sl,Ge,Sn). IV-Silylated aziridines can be prepared from ethyleneimine by amination of chlorosilanes in the presence of an HC1 acceptor, by dehydrocondensation with an organosilicon hydride or by cleavage of a silicon—carbon bond in 2-furyl-, 2-thienyl-, benzyl-, or allylsilanes in the presence of an alkali metal catalyst (262—266). N-Silylated aziridines can react with carboxylic anhydrides to give acylated aziridines, eg, A/-acetylaziridine [460-07-1] in high yields (267). At high temperatures, A/-silylaziridines can be dimerized to piperazines (268). Aldehydes can be inserted... 

V-acyl aziridines therefore behave like Weinreb amides (see p. 300), and stabilization of the tetrahedral intermediate by chelation may also play a role. Esters, of course, typically react twice with organolithiums to give tertiary alcohols. 

The s character of the aziridine nitrogen s lone pair has other effects too. The lone pair interacts very poorly with an adjacent carbonyl group, so N-acyl aziridines such as the one you saw on p. 1125 behave not at all like amides. The nitrogen atom is pyramidal and not planar, and the stretching frequency of the C=0 bond (1706 cm-1) is much closer to that of a ketone (1710 cm-1) than that of an amide (1650 cm-1). 

Lack of conjugation leads to increased reactivity, and N-acyl aziridines are useful in synthesis because they react with organo-lithium reagents only once to give ketones. No further reactions of the product ketone occur because the N-acyl aziridine is reactive enough to compete with it for the organolithium reagent. 

Oxophilic early transition metal Lewis acids were shown to react differently from azaphilic Lewis acids when ring-opening of acylaziridines was attempted [21], When A -acyl aziridine 48 was treated with trimethylsilylazide in the presence of a catalytic amount of Cp2Zr(SbF6)2, the product was azide-amide 49, whereas in the presence of Cu(OTf)2 the ring-expansion product, oxazoline 51, was formed (Sch. 1). 

The reactions of N-acyl aziridines can sometimes involve nucleophilic attack at the acyl group rather than the aziridine ring. This change in the more typical pattern of reactivity is dependent on a number of factors. An example of this type of change in reactivity has recently been reported <06TL2065>. Treatment of 118 with benzylamine provided a low yield of 119, the product of nucleophilic attack at the carbonyl. An examination of reaction conditions found that the use of a Lewis acid and a coordinating solvent such as Et O or THE provided significantly better yields of 119. 

The s character of the aziridine nitrogen s lone pair has other effects too. The lone pair interacts very poorly with an adjacent carbonyl group, so N-acyl aziridines such as the one you saw on p. 

A/-acyl aziridines therefore behave iike Weinreb amides (see p. 000), and stabiiization of the tetrahedrai intermediate byoheiation mayaiso piay a roie. Esters, of course, typicaiiy react twice with organoiithiums to give tertiary aicohois. 

Verglichen mit gewohnlichen tert. Amiden besitzen N-Acyl-aziridine eine stark ver-minderte Konjugation innerhalb der Amid-Gruppe (IR-Carbonylbande bei 1730 cm-1) und sind sterisch anspruchslos229,230. 

Auch die N-Acyl-aziridine lassen sich vorteilhaft mit aquimolaren Mengen Carbonsaure-chlorid, Aziridin und Triethylamin in situ" hcrstcllen. 

Compound 48 is 0-mesylated at C(3) with methanesulfonyl chloride in pyridine to obtain 49, and this is then treated with sodium hydroxide in hot 2-methoxyethanoI to instigate ring closure to the epimine 44. Because A-acyl aziridines are base-labile, the A-deprotected aziridine 44 is the final product that actually emerges from this reaction, which was highly desirable for the purposes we had in mind. 

Unusually stable azomethine ylides (39) have been produced by the UV-induced cleavage of suitably substituted fused isoxazolines. It was proposed that the reaction proceeded via an initial symmetry-allowed conversion to an acyl aziridine (38) followed by ring opening. On heating, the azomethine ylides were converted to tetrahydroindolizines (Scheme 10) <94MI 810-01). 

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