Aziridines 1-sulfonyl

Saito has recently reported high yields and enantioselectivities in aziridine synthesis through reactions between aryl- or vinyl-substituted N-sulfonyl imines and aryl bromides in the presence of base and mediated by a chiral sulfide 122 (Scheme 1.41) [66]. Aryl substituents with electron-withdrawing and -donating groups gave modest transxis selectivities (around 3 1) with high enantioselectiv-... 

Sulfonylaziridine 243 was halogenated in carbon tetrahalides in the presence of KOH as base [86] (Scheme 5.61). Although other examples of electrophile trapping of sulfonyl- and phosphonyl-stabilized metalated aziridines exist, the reactions were not stereoselective [87]. 

Both regioisomers were observed in aminohydroxylation of almost all the substrates that were examined. By taking advantage of their high combined yields, as well as the racemic nature of the aminohydroxylation products, a one-pot, two-step synthesis of sulfonyl aziridines through the cyclodehydration of hydroxysulfona-mides was developed (Scheme 12.18). 

Scheme 12.18 Synthesis of N-sulfonyl aziridines from 1,2-hydroxysulfonamides with DBU as a base.

Scheme 12.20 Influence of the nitrogen substituent (sulfonyl, acyl) on the regioselectivity of aziridine opening.

Scheme 12.21 Opening of sulfonyl aziridines with thiolates.

Unactivated aziridines, such as 24, are not as reactive as their N-sulfonyl analogues. Nevertheless, in aqueous conditions they react with different nucleophiles, as Scheme 12.23 illustrates. Treatment with buffered azide at 50 °C gave 25 in 90% yield. Hydrazine proved potent even at room temperature and 26 was fonned in 95 % yield, while phenyltetrazole required heating at reflux in water. The resulting amines participated in dipolar cycloadditions with alkynes and condensations with P-diketones. 

Reactive structures that interfere with the biochemical assay (aldehydes, acyl-halides, sulfonyl-halides, Michael acceptors, epoxides, aziridines, oximes, N-oxides). 

Recently, Scott et al. have reported that a Cu complex bearing an axially chiral ligand (49) is an excellent catalyst for aziridination of 2,2-dimethylchromene and cinnamate esters (Scheme 36), though it is also less efficient for the reactions of simple olefins.157,158 On the basis of DFT investigation of the nitrenoid intermediate (50), one of the oxygen atoms of the A -sulfonyl group has been proposed to be interacting with the nitrene N-atom.158... 

One of the most well used methods for the synthesis of aziridines involves a two (or sometimes more) step process in which an epoxide is opened by a nitrogen nucleophile. The resulting P-amino alcohol (e.g. 79) is then converted to an aziridine via a number of different processes. This method is generally not broadly applicable when a variety of different groups on the nitrogen of the aziridine are desired. A useful method to convert an epoxide to a number of different /V-sulfonyl aziridines (e.g. 80) has been reported <06S425>. Simple addition of a sulfonamide to an epoxide provides high yields of 79 which is readily closed to form the aziridine. 

Substituted aziridines have been used to form homobifunctional and trifunctional crosslinking agents, although their use has been limited (Ross, 1953 Alexander, 1954). The functional group has found use, however, in the design of the fluorescent probe dansyl aziridine (5-dimethylaminonaphthalene-2-sulfonyl aziridine) (Johnson et al., 1978 Grossman et al., 1981). 

Decomposition of sulfonyl azides was shown to be catalyzed by copper in 1967 (72, 73). In the presence of alkenes, the reaction provides both aziridines and the C-H insertion products, albeit in low yields (73). In 1991, Evans et al. (74, 75) illustrated that both Cu(I) and Cu(II) salts were effective catalysts for nitrenoid transfer from [A-(/Moluenesulfonyl)imino]phenyliodinane (PhI=NTs) to a variety of acceptor alkenes. In the absence of ancillary ligands, reactions proceed best in polar aprotic solvents such as acetonitrile. Similar results are observed using both Cu(MeCN)4C104 and Cu(acac)2 as precatalysts, Eq. 53. 

They transformed L-serine in seven steps to the iV-2-(trimethylsilyl)ethyl-sulfonyl(SES)-protected aziridine 104. The latter reacted with the lithio-an-ion of ( )-3-phenyl-l-(phenylsulfonyl)-2-propene (105) to a diastereomeric mixture of the sulfones 106 (Scheme 27). This mixture was treated with TBAF, yielding the pyrrolidine 107 as a single diastereoisomer with 2,3-frans-2,5-czs-configuration previously observed for 5-endo-trig cyclizations of this type. In three additional steps the pyrrolidine 107 was transformed to (+)-preussin (2), with 5% yield overall and in twelve steps altogether. 

Kwart and Kahn have found that benzenesulfonyl azide forms a complex with freshly reduced copper powder.189 190 This copper azide complex decomposes at a lower temperature than the pure sulfonyl azide. In refluxing methanol, benzene-sulfonamide (27) is isolated as the major product. In the presence of dimethyl sulfoxide, N-benzenesulfonyldimethyl-sulfoximine (28) is obtained in almost quantitative yield. In cyclohexene solution benzenesulfonamide (29), N-benzenesul-fonyl-7-azabicyclo[4.1.0]heptane (30), and 1-cyclohexenylben-zenesulfonamide (31) are isolated as the main reaction products. According to the authors, Schemes VII and VIII represent an acceptable interpretation of the experimental data.189 190 In pure alcohol, the decomposition should occur by two competitive reactions (Scheme VII) producing benzenesulfonamide together with a ketone and oxidized copper. These last two products have indeed been observed in the reaction mixture. In the presence of DMSO, it seems that a copper-nitrene intermediate is formed which is trapped by DMSO. In cyclohexene solution, the authors have observed that the aziridine (30) disappears from the product composition when DMSO is added. The yield of enamine 31, however, is... 

Sulfonyl azides react with olefins at a temperature which is much lower than the decomposition temperature of the azides (120-150°). The isolated products are aziridines and anils. The addition can be conceived as a result of two consecutive reactions, namely a 1,3-dipolar cycloaddition of the azide to the olefin immediately followed by decomposition of the formed unstable triazoline. As no triazolines can be detected, these reactions can also be regarded as a concerted addition with concomitant loss of nitrogen. 

Tertiary amines have been shown to react with isocyanates in an analogous fashion to form ureas (41—43). Similarly, aziridines (three-membered rings containing nitrogen) are found to react with isocyanates to yield cyclic ureas. Tertiary amines have also been shown to form labile dipolar 1 1 adducts with isocyanates reminiscent of salt formation. In contrast, formaldehyde A/,Ai-acetal aminals form insertion products with sulfonyl isocyanates (44,45). 

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