Enones aziridination

Aziridinations of enones using Cinchona-hased phase-transfer conditions are so far rare and have not been as successful and generally applicable as is the case for epoxidation reactions. In contrast, iminium catalysis using primaiy Cinchona-derived amines again provided excellent solutions for enone aziridination. 

When the enone 218, possessing a methyl group at the C(2) position, was treated with NaN3 in DMF, aziridine 219 was isolated as the only product (46) (Scheme 9.46). This reaction was adopted for the total synthesis of ( )-desamyl-perhydrohistrionicotoxin (224) from the azido enone 220. 

Molander and Hiersemann (60) reported the preparation of the spirocyclic keto aziridine intermediate 302 in an approach to the total synthesis of (zb)-cephalotax-ine (304) via an intramolecular 1,3-dipolar cycloaddition of an azide with an electron-deficient alkene (Scheme 9.60). The required azide 301 was prepared by coupling the vinyl iodide 299 and the aryl zinc chloride 300 using a Pd(0) catalyst in the presence of fni-2-furylphosphine. Intramolecular 1,3-dipolar cycloaddition of the azido enone 301 in boiling xylene afforded the desired keto aziridine 302 in 76% yield. Hydroxylation of 302 according to Davis s procedure followed by oxidation with Dess-Martin periodinane delivered the compound 303, which was converted to the target molecule (i)-cephalotaxine (304). 

Conjugate addition of amines to ct,P-enones (10,9).8 This reaction had been used to effect addition of aziridine to withaferin A (1). The product (2) has significant nnlitumor activity. 

An efficient and highly selective synthesis of bicyclic-a-keto aziridines (89) from 2-bromocyclopent-2-enone (88) and aliphatic primary amines, mediated by phase-transfer catalysts (PTCs) in water at room temperature, has been demonstrated.139... 

The intramolecular 1,3-cycloaddition of azidoalkyl cyclohexenones occurred smoothly when the temperature range was between 80-110 °C, however, aziridines were obtained from the intermediate dihydrotriazoles il the correct substitution pattern and regiochemical arrangement were present, cf. formation of 13 and 14 vs. IS131,132. The reaction was applied to the formal total synthesis of ( )-desamylperhydrohistrionicotoxin132. Direct nitrene enone addition can not be ruled out when the reaction is performed in refluxing xylene. 

The dipolar cycloaddition of an alkyl azide with an alkene to form an aziridine has been exploited in the total synthesis of the alkaloid ( )-aspidospermidine <20050BC213>. Enone 353 was prepared in 11 steps from 3-ethoxycyclohexenone and coupled to 2-iodo nitrobenzene under Ullman cross-coupling conditions. The acetate group of 354 was hydrolyzed and the resulting alcohol converted to an azide using standard conditions in 75% overall yield. The cycloaddition of the azide with the enone was conducted in refluxing benzene for 3 days. The fused-ring aziridine 355 was the only product isolated. None of the initial dipolar cycloadduct triazoline was observed. The... 

Aziridination of Enones Using Cinchona-Based Chiral Phase-Transfer Catalyst... 

The reaction of a-bromo-a, -enones with ammonia or amines proved to be a more universal synthetic method, permitting a wide variation of substituents at the nitrogen atom of the aziridine ring (94IZV282). 

Cyclopropanation. The reaction of the ylide with enones can be performed in the solid state (yields 79-91%) using KOH as base. Under the same conditions epoxides and aziridines are obtained from saturated ketones and imines, respectively. 

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