Aziridines A-tosyl

An alternative preparation of aziridines reacts an alkene with iodine and chloramine-T (see p. 1056) generating the corresponding A-tosyl aziridine. Bromamine-T (TsNBr Na ) has been used in a similar manner." Diazoalkanes react with imines to give aziridines." Another useful reagent is NsN=IPh, which reacts with alkenes in the presence of rhodium compounds or Cu(OTf)2 to give N—Ns aziridines. Manganese salen catalysts have also been used with this reagent. ... 

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). 

J0rgensen and coworkers reported the preparation of A-tosyl aziridines 19-20 by the net carbene addition (via a diazo compound) to A-tosyl iminoesters with either copper or silver catalysts.13,14 It was noted that the copper catalysts were generally superior, although a catalyst derived from AgSbF6 and (R)-Tol-BINAP provided the corresponding aziridine 19 from 16 and trimethylsilyl diazomethane 17 (R = TMS) in excellent chemical yield with high levels of diastereoselectivity, but unfortunately the enantioselectivity was poor (Scheme 8.3). This success with trimethylsilyldiazo-... 

The reaction is somewhat selective for the cis-diastereomer. The use of chiral additives in this reaction leads to aziridines enantioselectively. " Imines can be formed by the reaction of an aldehyde and an amine, and subsequent treatment with Me3SiI and butyllithium gives an aziridine. " A-Tosyl imines react with diazoalkenes to form A-tosyl aziridines, with good cis-selectivity " and modest enantioselectivity in the presence of a chiral copper catalyst, " but excellent enantioselectivity with a chiral rhodium catalyst. . It is noted that A-tosyl aziridines are formed by the... 

Oxaziridines are converted to ring-expanded lactams under photochemical conditions. A-Tosyl aziridines with an a-hydroxyalkyl substituent give a pinacol rearrangement product in the presence of Lewis acids, such as Sml2> in this case a keto-A-tosyl amide. ... 

Epoxides have been found to cleanly react with acetic anhydride to provide the diacetate under solvent-free conditions <06TL6865>. Treatment of epoxides with ammonium-12-molybdophosphate and a slight excess of acetic anhydride (1.2 equivalents) provides the corresponding diacetate in excellent yields. A number of epoxides were examined and all worked quite well. It was also found that A-tosyl aziridines participate in this reaction providing the corresponding acetoxysulfonamides. 

While nitrogen sources such as chloramine-T and Phl=NTs have been used for aziridination reactions, TsNClj has not been explored until now. The reaction of TsNCl, with Pd(OAc)j and K CO, provides the expected A-tosyl aziridines in good yields <06TL7225>. This reaction presumably proceeds through an initial amidohalogenation reaction catalyzed by palladium. The chloroamide is then converted to the aziridine via an intramolecular substitution reaction. 

An electrophilic metal-carbene complex intermediate has been proposed in the cyclopropanation reaction, whereas a paramagnetic copper nitrene species, which behaves as an electrophilic, nitrogen-centered radical, is proposed as the intermediate for the aziridination reaction.45 [Cu(Tp GF3 2)(C2H4)] is a good aziridination catalyst, readily converting a variety of olefins into the corresponding A-tosyl aziridines.46... 

A number of catalysts have been used to promote ring opening of A-tosyl-aziridines, such as phospho-molybdic acid and silica gel, for azide, cyanide and alcohols " and tri-n-butylphosphine for thiols and amines. Opening with iodide occurs at room temperature with iodine and thiophenol in the presence of air. In the nucleophilic ring opening of A-tosyl-aziridines, silver ion catalysis facilitates reactions with electron-rich arenes or hetarenes. ... 

A-Tosyl-aziridines (and A-tosyl-azetidines) react with cyclic enol ethers and enamides, under Lewis acid catalysis to give synthetically useful bicycles. ... 

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%). 

Solladie-Cavallo, A., Roje,M., Welter, R. and Sunjic, V. (2004) Two-step asymmetric synthesis of disubstituted A-tosyl aziridines having 98-100% ee use of a phosphazene base. The Journal of Organic Chemistry, 69, 1409-1412. 

Direct preparation of an aziridine from an alkene is possible by reaction of the alkene with a nitrene or metal nitrenoid species. Nitrenes can be generated thermally or photochemically from azides, although their reaction with alkenes to give aziridines is often low yielding and is complicated by side reactions. Oxidation of iV-amino-phthalimide or related hydrazine compounds (e.g. with Pb(OAc>4 or by electrolysis) and reaction with an alkene has found some generality. The metal-catalysed reaction of nitrenes with alkenes has received considerable study. A variety of metal catalysts can be used, with copper(II) salts being the most popular. For example, styrene was converted to its A-tosyl aziridine 72 by reaction with [A-(tosyl)imino]phenyliodinane (PhI=NTs) and copper(II) triflate (5.75). ... 

Aryl-A-tosyl aziridines react quantitatively, with the carbon nucleophile generated from 2-(bromoaryl)acetonitriles and t-BuOK, at the benzyl carbon in a highly regio-and stereo-selective 5 2 reaction. Subsequent treatment of the ring-opened product gives an excellent yield of a tetrahydroquinoline in a stereospecific, Pd-catalysed, intramolecular displacement reaction. 

An analogous transformation with A-tosyl aziridines produces A/-tosyl imines When aziridine 15 was treated with boron trifluoride-diethyl etherate in the presence of 2,3-dimethylbutadiene, amine 17 was produced via imine 16. 

A Lewis acid-promoted tandem rearrangement/reduction of non-racemic a-hydroxy epoxides yields 2-quartemary-l,3-diols. This reaction also successfully transforms a-hydroxy-A-tosyl aziridines into A-tosy 1-1,3-amino alcohols. 

Scheme 14.11 NHC-catalyzed oxidative, ring-opening reactions of A -tosyl aziridines with aldehydes.

Zhang and coworkers reported a Y(OTf)3-catalyzed formal [3 + 2]-cycloaddition of alkenes with azomethine ylide, providing highly substituted pyrrolidines with moderate to excellent di-astereoselectivity. The azomethine ylide was generated from a selective carbon-carbon bond cleavage of the corresponding A-tosyl aziridine under the mild reaction conditions (eq 13). ... 

Scheme 2.64 Synthetic routes to racemic and nonracemic 1,2,3,4-tetrahydroquinoxalines via the ring opening of A -tosyl aziridines...

Ghorai et al. reported on regioselective ring opening of monosubstituted A -tosyl aziridines 230 with different aliphatic and aromatic carbonyl compounds, followed by alkylative cyclization with C—N bond formation to give 1,3-oxazolidines 232 with high yields, excellent cis selectivity, and good enantiomeric excess.The oxazolidines can be easily converted into nonracemic amino alcohol 233 by mild acidic treatment (Scheme 40.49). 

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