Tosyl aziridine

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. ... 

While nitrogen sources such as chloramine-T and PhI=NTs have been used for aziridination reactions, TsNC12 has not been explored until now. The reaction of TsNCL, with Pd(OAc)2 and K2C03 provides the expected N-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. 

Non-metal catalyzed aziridinations have also been reported. These methods are often more broadly applicable than the metal-catalyzed methods. The use of iV-methylpyrrolidine-2-one hydrotribromide (MPHT) and chloramine-T is an effective route for the synthesis of iV-tosyl aziridines <06MI16>. The aziridination of olefins using i-BuOI and sulfonamides appears to be a general method for aziridination <06CC3337>. The i-BuOI is prepared in situ from t-BuOCl and Nal. This is a broadly applicable method in that a wide variety of sulfonamides (tosyl, nosyl, SES) can be used with roughly equivalent yields. 

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. 

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). 

Scheme 8.13 and Eqs. 8.6-8.10 reveal that lithiated methoxyallene 42 is sufficiently reactive towards a variety of electrophiles such as alkyl halides [44, 45], ethylene oxide [12c], tosylated aziridine 45 [46], dimethyl disulfide [12b], trialkylstannyl and trialkylsilyl chlorides [47, 48] and iodine [49]. These substitution reactions proceed with excellent regioselectivity and the corresponding a-functionalized products are obtained in good to high yields. An exceptional case was found by treatment of 42 with a guanidinium salt, which led to a 60 40 mixture of a- and y-adducts 50 and 51 (Eq. 8.11) [50],... 

Additionally, Wu and co-workers have shown regioselective ring-opening of aziridines with acid anhydrides mediated by imidiazolinylidene 3 [157]. This pathway requires the use of an electron withdrawing tosylated aziridine 310 in order for the reaction to proceed. The mild reaction conditions allow for a variety of products to be formed in high yields (Table 25). 

The ring opening of the tosyl-aziridine (64) with 1-thiofucose (30b) in the presence of sodium methoxide in methanol under reflux gave a mixture of thiodisaccharide (65a) and (66) in a 2 1 ratio in very good yield. Compound (65a) was then converted into (65b) (Scheme 21) [32]. 

In the following example the ring opening of Af-tosyl aziridines was used to prepare homochiral 0-tosylaminocarbonyl compounds [280] in good to excellent yields. 

Direct reaction of hydrocyanic acid with ethyleneimine does not yield the desired p-aminopropionitrile (68). However, ring opening of tosylated aziridines to give the corresponding tosylated p-aminopropionitriles is possible using trimethylsilyl cyanide [7677-24-9] with lanthanoid tricyanide catalysis (69,70). 

Rhodium perfluorobutyramide, (pfm)4Rh2, has been shown to catalyse the conversion of alkenes to trichloroethoxysulfonyl, nosyl, and tosyl aziridines on reaction with the corresponding sulfonamide and PhI(OAc)2.97... 

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 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. 

A facile phase-transfer catalysis protocol was reported for the conversion of p-hydroxy-a-amino esters into enantiomerically pure /V-tosyl aziridine-2-carboxylates <07TL6509>. Utilization of the same methodology allowed for preparation of an aziridine carboxamide in essentially quantitative yield. 

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>. 

Copper(II) acetylacetonate was used as catalyst in the diastereoselective aziridination of the homochiral protected cts-diol 5. The JV-tosyl aziridine 6 obtained was converted to ( + )-pan-crastatin121. 

This catalytic system was successfully applied to the alkynylation of tosyl aziridine with adjacent ether functionality this should provide a promising method for the synthesis of amino alcohols. Treatment of tosyl aziridine 81 with PhC CLi in the presence of catalytic Mc3Al in toluene at 0 °C for 5 h gave rise to the corresponding alkynylation product 82 in 66 % yield (Sch. 53), whereas reaction in the absence of Me3Al proceeded sluggishly under similar reaction conditions (7 % yield). The control experiment with simple aziridine 83, in which addition of catalytic McaAl had almost no influence on the reaction rate, supports the proposed catalytic cycle its efficacy is based on the formation of the pentacoordinate organoaluminum complex. 

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