Aziridine salts, ring opening

Reactions with Oxiranes, Oxetanes, and Aziridines. Lewis acids, lanthanide salts, and titanium tetraisopropoxide or aluminum isopropoxide catalyze the reactions of cyanotri-methylsilane with oxiranes, oxetanes, and aziridines, yielding ring-opened products. The nature of the products and the regio-selectivity of the reaction are primarily dependent on the nature of the Lewis acid, the substitution pattern in the substrate, and the reaction conditions. Monosubstituted oxiranes undergo regiospe-cific cleavage to form 3-(trimethylsiloxy)nitriles when refluxed with a slight excess of cyanotrimethylsilane in the presence of a catalytic amount of potassium cyanide-18-crown-6 complex (eqs 8-10). The addition of cyanide occurs exclusively at the least-substituted carbon. 

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). 

The cationic ring opening polymerization of oxolane (THF) or of N-substituted aziridines can be initiated by oxocarbenium salts [42]. The methacrylic ester unsaturation is insensitive to cationic sites, and polyoxolanes (poly-THF) macromonomers are obtained in good yields. 

Fe(OTf)2-catalyzed aziridination of enol silyl ethers with PhlNTs followed by ring opening led to a-N-tosylamido ketones in good yields (Scheme 27) [81]. With silyl ketene ketal (R = OMe) as substrate, the N-tosyl-protected amino acid ester was obtained in 50% yield. In contrast, the copper (I) salt CuClOq was found not effective for this substrate [82]. 

The same regiochemistry is observed when nitroimidazole (48-2, 48-3) acts as a nucleophile in unionized form. Thus, the reaction of a compound with benzoyl-aziridine (49-1) in the presence of boron trifluoride probably involves an initial salt formation with an amide attack by the imidazole results in a ring opening and the formation of the alkylated product (49-2) the free primary amine (49-3) is obtained on basic hydrolysis. Acylation of the primary amine with methyl thiochloroformate gives the corresponding thiourethane, carnidazole (49-4) [52]. 

Some of the more important monomers whose ring opening polymerisations have been induced by stable cation salts include, 1,4-epoxides, notably tetra-hydrofuran (20,112,113), 1,2-epoxides (114), 1,3-episulphides (thietans) (33,53), 1,2-episulphides (thiiranes) (53), azetidines (115,116), aziridines (117), the cyclic formals, 1,3-dioxolan (23,54, 118-120), and 1,3-dioxepan (118,119), trioxane (121,122) and more recently lactones (123). Aldehydes (124) may also be included since these molecules can be regarded as the smallest possible oxygen hetero-... 

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). 

Several studies on the reactions and preparation of aziridines have been published. The ring opening of 2-substituted aziridines, accomplished by first converting them into aziridinium salts by reaction with a benzyl bromide and then attack of the bromide counter ion, gave only one bromide in a regio- and stereo-specific reaction.43 Since attack by the bromide ion of the aziridinium salt only occurred at the most substituted carbon with an inversion of stereochemistry, it was concluded the reaction occurred by an SN2 mechanism. This was supported by calculations at the MPWBlK/6-31+G(d) level of theory for reactions featuring two solvating acetonitrile molecules embedded in an acetonitrile matrix. 

A strategy for the synthesis of trehazolamine has been developed from 1-methox-yethoxymethyl-3-pivaloyloxymethylpyridinium perchlorate via amino cyclopentane derivatives (Schemes 42 and 43).115 Pyridinium salt 351 was prepared by a two-step sequence from 3-(hydrooxymethyl)pyridine 349 via 350 (Scheme 42). Irradiation of 351 in aqueous NaHC03 led to production of the separable bicyclic aziridines 352 (20%) and 353 (16%). Ring opening of 352 by acetic acid, followed by removal of the... 

Sometimes, especially when fluoride sails are used as the reagents for the ring opening of aziridines, the substrate can be activated by quaternization to the corresponding A/.A-dialkyl-aziridinium compound, which reacts more readily with the fluoride anion than the aziridine itself. Thus, the tV.A -diallylaziridinium mesylate salts 23 have been employed in ring opening reactions of aziridine derivatives of pyranosides. " " ... 

With trifluoromethyl-substituted azomethine ylides, generated in situ by the ring opening of CAV-2-bcnzoyl-l -methyl-3-(trifluoromcthyl)aziridine (2)124 or by protonation of trifluoro-methylated thioamidinium salts, 25 1,3-dipolar cycloadditions with both electron-deficient and electron-rich alkenes can be achieved rcgiosclcctively. However, stereoselectivity depends on both the ylide configuration and electronic interactions. 

Furthermore, the ring opening of the aziridinium salt 181, prepared from the aziridine 172 with methyl iodide at low temperature, by reaction with a number of nucleophiles also yielded the isoquinuclidine derivatives 182 predominantly, together with the isomer 183 (Scheme 35). 

Pyrrolizidine alkaloids ( )-trachelanthamidine (240) and ( )-supinidine (244) were synthesized, based on the Michael addition of an aziridine to an a,/J-unsaturated ester and subsequent ring opening of an aziridinium intermediate. Interest in these alkaloids stems from their biological activities. Treatment of ethyl 6-chloro-2-hexenoate (236) with excess aziridine at 0°C gave the pyrrolidine derivative 238 in one step, probably via the aziridinium salt 237 in 73% yield. The intramolecular cyclization of 238 with lithium diisopropylamide in tetrahydrofuran provided the thermodynamically more stable ester 239 as the sole product, (86%), which was then converted to ( )-trachelanthamidine (240) by reduction with lithium aluminum hydride. Since necine bases must contain a 1,2-didehydro system in their molecule to exhibit physiological activity, the following reactions were carried out to introduce a 1,2-didehydro system. Treatment of 238 with 2.4 equiv of lith-... 

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