Aziridines substituted with

Garner et al. (90,320) used aziridines substituted with Oppolzer s sultam as azomethine ylide precursors. The azomethine ylide generated from 206 added to various electron-dehcient alkenes, such as dimethyl maleate, A-phenylmalei-mide, and methyl acrylate, giving the 1,3-dipolar cycloaddition product in good yields and up to 82% de (for A-phenylmaleimide). They also used familiar azomethine ylides formed by imine tautomerization (320). Aziridines such as 207 have also been used as precursors for the chiral azomethine ylides, but in reactions with vinylene carbonates, relatively low de values were obtained (Scheme 12.59) (92). 

Quinze, K. Laurent, A. Mison, P. Synthesis of secondary aziridines substituted with a trifluoromethyl group. J. Fluorine Chem. 1989, 44, 211. 

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

This is by far the most versatile route to the synthesis of ester-substituted aziridines, especially as the benzhydryl group can easily be cleaved by hydrogenolysis. Wulff has applied this methodology to a short asymmetric synthesis of the antibiotic (-)-chloramphenicol in four steps from p-nitrobenzaldehyde (Scheme 1.34) [61]. In this case it was found that treatment of the aziridine 111 with excess dichloroacetic acid gave the hydroxy acetamide directly, so no separate deprotection step was required. 

N,N-Dibenzyl (z -amino a-chloroketimines 202 can be prepared from the corresponding ketones, which in turn are available by the addition of chloromethyllithium to esters of natural cz-amino acids. Reduction of 202 with sodium cyanoborohydride directly afforded a-aminoalkyl-substituted aziridines 203 with high syn diastereoselectivity, which was only moderately affected by the size of the substituent [96] (Scheme 30). A complemen-... 

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). 

Sharpless asymmetric dihydroxylation procedure was applied to the synthesis of the side chain of azinomycin A (equation 26)43. Horner-Emmons condensation of phospho-nate 36 with a /J-aziridine substituted acrolein afforded dehydroamino acid diene 37. Treatment of the diene with catalytic amounts of an osmium reagent and dihydroquini-dine (DHQD) p-chlorobenzoate resulted in asymmetric dihydroxylation, producing diol 38. Diol 38 was further converted to the naphthyl ester. 

A -acylaziridines substituted with an electron-withdrawing group produce a 2,4-disubstituted oxazoline as the major product. Borontrifluoride etherate (BF3 OEt2) has also been used successfully for an Al-benzoyl, but not an N-acetyl-substituted aziridine (Scheme 8.58). ... 

H-Aziridines. In the presence of BF3 etherate, this reagent adds to double bonds substituted with three cyano or carboalkoxy groups to give an adduct that is converted into a I //-aziridine by treatment with triethylamine. 

Reaction with Carbon Nucleophiles. Unactivated aziridines react with the lithium salts of malonates or p-keto esters in the presence of lithium salts to yield 3-substituted pyrrolidinones (56—59), where R = alkyl and aryl, and R = alkoxyl, alkyl, and aryl. 

Triazolines substituted with two electron-withdrawing groups in the 4-position (Scheme 83) also yield aziridines as the sole products of thermal decomposition when the 1-substituent is aryl319,321,322 when one of the electron-withdrawing substituents is an acyl group, the aziridine isomer-izes spontaneously to the oxazoline via the azomethine ylide (Scheme... 

Similar to these results, but accompanied with ring opening, are the desilylation reactions of substituted aziridines. Treatment with cesium fluoride (1 equiv.) in HMPA (tetrabutylammonium fluoride in THF or DME gives lower yields) at room temperature followed by aqueous work-up, yields desilylated open-chain compounds.320... 

Garner et al. [49] have synthesized the 6-exo-substituted 3,8-diazabicydo [3.2.1] octane core of DNA reactive quinocarcin alkaloid 99 by cydoaddition of the azomethine ylide 101, generated by irradiation (A. — 254 nm) of the corresponding aziridine 100, with Oppolzer s chiral acryloyl sultam (102). This produced 6-exo-subs tituted cycloadducts 103 104 in 25 1 diastereoselectivity (Scheme 8.30). 

Aziridinyllithiums are configurationally stable even when adjacent to a carbonyl group.58 For example, treatment of the ester 116 with LDA and then BuLi at -75 °C, maintaining the organolithium 117 at this temperature for 20 min, and then quenching with Mel, MeOD or MeOH, returned the aziridine 118 with no loss of enantiomeric purity.59 However, the thioester-substituted aziridinyllithiums 120 and 123 showed some degree of interconversion as the temperature was raised. 120 is clearly more stable than 123, since 123 demonstrated configurational instability even within 15 min at -95 °C. 120 showed only small amounts of inversion even at -60 °C. 

The p-amino-a-hydroxy esters have been converted to diamino acids [88, 89] and related compounds like the nitrogen-substituted azetidinone shown in Scheme 13, a key structure in the synthesis of the commercially available antibiotic loracarbef [90] by substitution of the alcohol moiety with an azide. Several approaches have been used to achieve this transformation. Mesylation of the alcohol followed by substitution with sodium or trimethylsilyl azide provided cis-diamino acids [88,89]. trans-Diamino acids were obtained by ring opening of the aziridine [88] or by inversion of the alcohol bearing carbon followed by substitution under Mitsunobo conditions [90]. 

The ring opening of enantiopure IV-tosyl aziridines 215 with 2-substituted 2-lithio-l,3-dithianes takes place at the less substituted carbon atom in good yields (59-92%)321. The corresponding adducts gave /9-tosylamino carbonyl compounds after reaction with methyl iodide under acetone reflux. 

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>. 

A palladium-catalyzed ring expansion of aziridines provided a novel route to highly substituted pyrroles <07TL2267>. Treatment of methylene aziridines 33 with Pd(0) in the presence of symmetrical 1,3-diketones 34 led to the formation of 3-ketopyrroles 35. Pyrrole-substituted nucleoside analogues were prepared using a vanadium-mediated transformation of 2-azirines in the presence of symmetrical 1,3-diketones <07SL2723>. 

The reactions of N-substituted iminophosphoranes 5 with alkyl or aryl isocyanates proceed under mild conditions to give aziridin substituted carbodiimides 6 (R = H, Ph R = Me, Ph, a-naphthyl), which are only observed in solution, and their yield is... 

These products have a varied and useful chemistry, for example, the stereochemistry of substitution with azide can be manipulated by optional formation of an intermediate aziridine (Scheme 90). ... 

J2.4 N-Acyl- and N-Cyano-aziridines and Related Compounds 3J2J S-Aminoaziridines, N-Phosphonylaziridines 3.52.6 Aziridines N-Substituted with OorS... 

Hydroxylamines also react with nonsymmetrical aziridines under Lewis-acidic conditions to give products of nucleophilic attack at the less-substituted site. Thus, treatment of methyl aziridine 55 with A -/-butylhydroxylamine 56 and 20mol% boron trifluoride etherate provides the diamine derivative 57 in 77% yield <2001TL8243>. Fluoride ion is a powerful catalyst for the reaction of aziridines with the weakly nucleophilic />-toluenesulfonamide, a phenomenon which has been applied with advantage toward the preparation of protected diamino diol 59, a precursor to the aminocyclitol substructure (Scheme 17) <2001TL6433>. 

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