Aziridines with cyclic ketones

Secondary amines used for reactions with cyclic ketones may be aziridine (52X azetidine (53), pyrrolidine (54), piperidine (55), hexamethylenimine (56), morpholine (57), //-methylpiperazinc (58) and acyclic amines like dimethyla-mine (59). The general order of electrophilic attack of enamines as dependent on the nature of the amine moiety decreases in the sequence pyrrolidine (54) > dimethylamine (59) > hexamethylenimine (56) > piperidine (55) sk azetidine (53) > morpholine (57). This sequence seems to parallel the magnitude of conjugative interaction between the amino group and the C=C double bond as indicated by the H NMR chemical shift of the hydrogen at the jS-carbon. 

Several substituted prohnamides, derived from chiral enantiopure aziridines, of general formula 42 (Figure 24.13), were used in aldol reactions. Optimization of the reaction conditions with cyclic ketones showed that no product was formed when the reaction was carried out in organic solvents such as CHCI3 and DMF. 

DMP with high purity by the original procedure therefore, a few modifications have been suggested. In addition, DMP has been successfully used in the syntheses of polycyclic heterocyclesand in the removal of thioketals and thioacetals. It should be mentioned that other hypervalent iodine compounds can be used as oxidants as well, especially for the o-iodoxybenzoic acid (IBX), the precursor to DMP, which can oxidize tertiary cyclic allyl alcohol into O, y0-unsaturated cyclic ketones and secondary amines into imines and can convert epoxides or aziridines into corresponding of-hydroxy ketones or Q -amino ketones. 

Linear aliphatic and aromatic a,P-unsaturated ketones 9 were selectively aziridi-nated using salt 11 as catalyst and carbamate 10a as nitrogen source (Scheme 27.4). These reaction conditions were also appUed to several cyclic enones, leading to the corresponding aziridines with 85-99% ee, depending on the cycle size [13]. 

Melchiorre and co-workers reported the first asymmetric aziridination of a,p-unsaturated ketones using the primary amine-amino acid salt 91 (Scheme 5.39) [68]. The reaction occurred via first nucleophilic addition of A-centered nucleophile (iminium catalysis) followed by intramolecular cyclization (enamine catalysis). Essential factors for the success of the current reaction included the proper selection of nitrogen nucleophile and the addition of solid NaHCO. Under the optimized conditions, a range of cyclic or acyclic enones can be incorporated in the protocol to afford either A-CBz or A-Boc aziridines with excellent diastereo- and enantioste-reocontrol (Scheme 5.39). 

Melchiore et al. reported highly stereoselective aziridinations of linear and cyclic a,p-unsaturated ketones with excellent diastereo- and enantio-selectivity (up to 99% ee). Aziridination was performed using N-protected hydrojylamines and a primary amine salt catalyst, made by combining 9-amino-9-deo)y-ep/-dihydroquinine (9-epz-DHQA) with o-N-Boc-phenylglycine (Scheme 15.8). The first step of the reaction is the nucleophilic addition of Af-protected hydro>ylamine to the iminium intermediate (formed from the enone and amine catalyst salt) followed by an intramolecular cyclisation of the resulting enamine to the aziridine product. 

Two cyclic olefins were resolved by coordination with dicarbonyl Rh(I)-3-tri-fluoroacetyl-lR-camphorate [23, 24]. Starting with this observation, Schurig and coworkers [25] have systematically explored stereoselective partitioning on optically active -diketonates of transition metals, and have extended the use of these selectors to the chiral differentiation of underivatized ketones and alcohols and to heterocyclic compounds such as oxiranes, aziridines, azetidines, thiiranes, tetrahy-drofuranes, etc. 

Alkylidene-3-oxazoline-5-ones have been prepared in the past by irradiation of suitably substituted aziridines or by less direct routes. The synthesis of these compounds without 2-alkylidine substituents has proved difficult but a simple and mild process has now been developed in which aliphatic aldehydes and ketones react with 7V-hydroxy-amino-acids in the presence of triethylamine (357) - (358). Under these same conditions aromatic ketones gave low yields of the cyclic products, whereas aromatic aldehydes gave only nitrones. 

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