Transition states aziridine reactions

Transition state energies have been determined by computation (PM3 and AMI) for the reaction of norbomadiene 74a (X=CH2) and 7-isopropylidenenorbomadiene 74b (X is C=CMe2) with the 1,3 dipoles 23 formed from ring-opening of the A -phenyl and A -benzyl derivatives of aziridine 22 (see, Table 1). These data demonstrate the preference for formation of exo,exo-isomers 75 with norbomadiene in the A -benzyl series, however the energy difference between the transition states for the A -phenyl series is much closer and accords with the drop in stereoselectivity. Introduction of the isopropylidene substituent into the 7-position of the dipolarophile favours formation of the bent-frame isomers 76, especially in the A -phenyl series. These predictions accord well with the stereoselectivities observed experimentally. 

Reaction of norbomadiene 74 (in excess) with 7V-benzyl aziridine 67 formed exclusively the all-sy l l-adduct 77. This stereochemistry, confirmed by NOE between Ha and Hb, resulted from attack at the underface of the dipole by the exo-face of the dipolarophile. Similarly, reaction of A -benzyl aziridine 67 with the diacetoxybenzonorbomadiene 30 gave a single adduct 78 (Scheme 11), the symmetrical structure of which was clearly apparent in the ll NMR spectrum. These stereochemical outcomes demonstrated that the transition state (TSa), in which the methano-bridge was adjacent to the (V-substituent, was favoured in the A -benzyl series (X and R small), and in accord with the semiempirical calculations. 

Further, a comparison of the effects of ligand on enantioselectivity in the cyclo-propanation and aziridination reactions revealed a linear relationship. Jacobsen argues that this reinforces the mechanistic analogy between these group-transfer reactions and suggests that the transition states are subject to similar selectivity determining factors. Finally, Jacobsen observed ligand acceleration with the diimines in this reaction. 

Chemla and Ferreira effected lithiozincation of TMS propargyl chloride to prepare chloroal-lenylzinc bromide reagents (Table 21)33. Subsequent reaction of these reagents with N-t-butyl-substituted sulfoximines yielded the related traws-sulfoxinyl aziridines, arising from internal displacement of the chloride substituent of the anti sulfinamide adduct. A transition state in which the f-BuSO group is eclipsed with the alkynyl (vs R) substituent accounts for the preferred formation of the major A-sulfinyl diastereomer (equation 41). 

Analogous methyl azidoformate forms with norbornene a thermal unstable triazoline.251 The decomposition products are 40% aziridine and 55% imide. Furthermore it has been observed that the rate of nitrogen evolution of the triazoline from methyl azidoformate increases threefold when triglyme and 20-fold when dimethyl sulfoxide are substituted for 1,1-diphenylethane as solvents. This fact supports a betaine intermediate in the thermal decomposition reaction. The triazoline from 2,4-dinitrophenyl azide and norbornene could just be isolated, but from picryl azide only the aziridine was obtained.252-254 Nevertheless, the high negative value of the activation entropy (—33.4 eu) indicates a similar cyclic transition state for both reactions. 

A general reaction of 1 -acyl-2- )r m-alkylaairidin B fa the pyrolytic rearrangement to an uneaturated amide1 . -SM (Eq, 72). Stereochemical evidence supports the view that the reaction involves the intramolecular aVdinination of a proton concerted with the opening, of the aziridine dug (transition state, XLVI). So... 

A recent instance225 of reaction 22 (X = NH) involves the reactions of some (het-eroarylchloromethyl)lithium (165) reagents with imines (166) to form 167 and to produce the heteroaryl aziridines (168) as depicted in Scheme 50. Aziridines (167) are obtained in the preferential (or exclusive) conformation E. A tentative explanation of this behaviour is the different steric compression in the transition states affording isomeric E or Z aziridines. 

Calculations at the MP2(Full)/6-31++G(d,p)//MP2(Full)/6-31+G(d) level of theory were used to investigate the SN reactions between ammonia and aziridine, aze-tidine, methylethylamine, and four fluorinated derivatives of aziridine.52 The results show that aziridine and azetidine have strain energies of 27.3 and 25.2 kcalmol-1, respectively, and that as a consequence they react 7.76 x 1023 and 2.30 x 1017 times faster with ammonia than does the methylene group of methylethylamine. However, even after subtracting the effect due to the release of ring strain, aziridine still reacts much faster than the other two substrates. This is because the electrostatic attraction of the charges in the product-like dipolar transition state are much greater for aziridine. 

Oxidation of primary N-aminobenzimidazole 32 with PhI(OAc)2 4 in the presence of olefins gives aziridines 34 [54]. Similar oxidations are effected by lead tetraacetate. The reaction was initially proposed to involve the intermediacy of AT-nitrene as a reactive species, thought to be produced through reductive a-elimination of amino-A3-iodane 33. Recent mechanistic studies on lead tetraacetate oxidation, however, suggests that the acetoxyamine 35 instead of AT-nitrene is the aziridinating species, and the reaction proceeds through a transition state 36 similar to that of epoxidation using peracids [55]. 

The following aza-Darzens reaction, in which a preformed lithium a-bromoenolate reacts with a sulphinimine to give an aziridine, features a six-membered transition state that accounts for the high diastereoselectivity ... 

To explain the enantioselectivity obtained with semi-stabilized ylides (e.g., benzyl-substituted ylides), the same factors as for the epoxidation reactions discussed earlier should be considered (see Section 10.2.1.10). The enantioselectivity is controlled in the initial, non-reversible, betaine formation step. As before, controlling which lone pair reacts with the metallocarbene and which conformer of the ylide forms are the first two requirements. The transition state for antibetaine formation arises via a head-on or cisoid approach and, as in epoxidation, face selectivity is well controlled. The syn-betaine is predicted to be formed via a head-to-tail or transoid approach in which Coulombic interactions play no part. Enantioselectivity in cis-aziridine formation was more varied. Formation of the minor enantiomer in both cases is attributed to a lack of complete control of the conformation of the ylide rather than to poor facial control for imine approach. For stabilized ylides (e.g., ester-stabilized ylides), the enantioselectivity is controlled in the ring-closure step and moderate enantioselectivities have been achieved thus far. Due to differences in the stereocontrolling step for different types of ylides, it is likely that different sulfides will need to be designed to achieve high stereocontrol for the different types of ylides. 

Nitrosyl halides add to alkenes references are scattered through the litnnture back to 1875 (ref. 194 and references cited therein). The adducts vary enormously in their stability, but when their structures allow they, like nonhalogenated nitroso compounds, isomerize to oximes or dimnize. The orientation of the reaction is consistent with an electrophilic medumism, in which the reagent is polarized as NO Hat. Bicyclic substrates and reaction media of low polarity favor syn addition, suggesting a four-center transition state (Scheme 81). Aziridine synthesis via NOCl/alkene adducts is discussed in Section 3.5.2.1. 

Heine ° has pointed out that this reaction represents an example of the reverse of the reaction on pyrolysis of imido esters. Heine has recently shown that the pyrolytic isomerization of cis- and rra j-l-p-nitrobenzoyl-2,3-diphenylaziridines into 2-p-nitrophenyl-4,5-diphenyl-2-oxazolines is a stereospecific process. These results are consistent with a mechanism that involves either a four-membered transition state or a short-lived tight ion-pair intermediate that collapses to the oxazoline before racemisation can occur . The pyrolysis of l,3-diaroyl-2-aryl-aziridines results in a different kind of reaction, in which a-benzamidobenzal-acetophenones are produced, viz. 

---