Terminal aziridination

Ruano has reported substrate-controlled asymmetric ylide aziridination by treatment of enantiopure sulfinyl imines 117 with dimethyloxosulfonium methylide 118 to form terminal aziridines [63], The chiral tert-butylsulfinyl group was shown... 

Direct deprotonation/electrophile trapping of simple aziridines is also possible. Treatment of a range of N-Bus-protected terminal aziridines 265 with LTMP in the presence ofMe3SiCl in THF at-78 °C stereospecifically gave trans-a, 3-aziridinylsi-lanes 266 (Scheme 5.67) [96]. By increasing the reaction temperature (to 0 °C) it was also possible to a-silylate a (3-disubstituted aziridine one should note that attempted silylation of the analogous epoxide did not provide any of the desired product [81],... 

Two recent reports described addition of nitrogen-centered nucleophiles in usefully protected fonn. Jacobsen reported that N-Boc-protected sulfonamides undergo poorly selective (salen) Co-catalyzed addition to racemic epoxides. However, by performing a one-pot, indirect kinetic resolution with water first (HKR, vide infra, Table 7.1) and then sulfonamide, it was possible to obtain highly enantiomer-ically enriched addition products (Scheme 7.39) [71]. These products were transformed into enantioenriched terminal aziridines in straightforward manner. 

The N-protected-2-aryl aziridines react smoothly with various thiols to afford the corresponding (3-aminosulfides (Fig. 9). In the cleavage of A/-benzyl- and Af-tosyl-2-aryl aziridines, preferential cleavage is at the benzylic position of the aziridine ring, whereas (V-tosyl-2-alkyl aziridines cleaves at the less hindered (terminal) aziridine-ring carbon. 

Regio- and stereo-selective deprotonation of (V-t-butylsulfonyl-protected terminal aziridines with LiTMP has generated a non-stabilized aziridinyl anion that undergoes in situ or external electrophile trapping under experimentally straightforward conditions to give tran.v-disuhstituted aziridines in good to excellent yields.92... 

The lithiation of /ra .s-A-alkyl-2,3-diphenylaziridines such as 51 was reported to be completely a-regioselective while the stereochemical course of the lithiation-trapping sequence was found to be solvent dependent <07OL1263>. Retention of configuration was observed in hexane, ether, or toluene, while coordinating solvents such as THF or toluene/crown ether produced inversion. Related isomerization and dimerization reactions of a-lithiated terminal aziridines were also reported <07JOC10009>. 

Terminal aziridines were deprotonated with LTMP and directly treated with a variety of electrophiles to provide substituted aziridines, 193 <05OL1153>. In all cases, the products had the trans geometry about the aziridine ring. Related work on the hthiation of carhoxylate substituted aziridines <05AG(I)6169> and aziridinium ions <05MI1294> was also reported. 

In all cases, enantioenriched a-chloroaldehyde products were isolable and could be subsequently readily functionalized. Alternatively, the enantioenriched a-chloroaldehyde products could be functionalized in situ (Scheme 13.22). Using the conditions developed by Jprgensen for the a-chlorination of aldehydes, in situ reductive amination and base-catalyzed intramolecular S 2 reaction generated chiral terminal aziridines in one-pot from achiral saturated aldehydes [50]. Enantioenriched terminal epoxides could be produced in one-pot from achiral saturated aldehydes using SOMO catalysis for the a-chlorination of aldehydes, followed by an in situ reduction and base-catalyzed Sff2 reaction [49]. 

Synthetic strategy Regioselective terminal aziridine opening - aminoacetylative cyclization cascades... 

Solution-phase DFT methods have been used to identify the source of the diastere-oselectivity in sulfur ylide additions to chiral A -sulfinyl imines, which - upon ring-closure - yield terminal aziridines. Ring closure is fast and irreversible, and the control due to the sulfur configuration is augmented by a favourable interaction between the sulfinyl oxygen and iminyl hydrogen. 

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