Keto aziridines

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). 

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... 

Ring expansion of keto aziridines to the 2,5-diaryloxazoles in the presence of dicyclohexyl carbodiimide and iodine has been reported. A tandem thia-Fries rearrangement of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate aryne precursors has been described (Scheme 76). ° ... 

Many a,/ -unsaturated keto steroids undergo conjugate addition and thereby provide a unique route to aziridines. Treatment of 3j5-hydroxypregna-5, 16-diene-20-one acetate (48) with methoxyl-or ethoxylamine in ethanol under... 

The Hoch-Campbell reaction of a-hydroxy ketoximes do not alter the course of the reaction although deprotonation probably took place concurrently for both the alcohol and the oxime. Treatment of oxime 40 afforded aziridine 42 in 30%, presumably via the intermediacy of azirine 41. a-Keto ketoximes would behave similarly to the a-hydroxy ketoximes in the Hoch-Campbell reaction after addition of the first equivalent of the Grignard reagent to the ketone. Therefore, the reaction between a-keto ketoxime 43 and phenylmagnesium bromide gave aziridine 45 in 41% yield, presumably via the intermediacy of azirine 44. 

No biosynthetic experiments have been reported for these compounds, but they probably all share the same biosynthetic mechanism. One possibility is that they are generated by cyclization of an a-amino-p-keto carboxyl intermediate that would arise from threonine (136) and sphingosine (131) for 139 and 130, respectively (Figure 11.23). Alternatively, cyclization may precede oxidation, with an aziridine intermediate being formed. 

The endo-spiro-OZT could be prepared through a reaction sequence similar to that applied for the exo-epimer, with spiro-aziridine intermediates replacing the key spiro-epoxides (Scheme 18). Cyanohydrin formation from ketones was tried under kinetic or thermodynamic conditions, and only reaction with the d-gluco derived keto sugar offered efficient stereoselectivity, while no selectivity was observed for reaction with the keto sugar obtained from protected D-fructose. The (R) -cyanohydrin was prepared in excellent yield under kinetic conditions (KCN, NaHC03, 0 °C, 10 min) a modified thermodynamic procedure was applied to produce the (S)-epimer in 85% yield (Scheme 18). 

Oxidative cleavage of the C(l)—C(2) bond of aziridines and 2-amino-1-cycloal-kanols, giving the corresponding keto... 

Cyanuric acid exists in two tautomeric forms corresponding to keto-enol tautomerism in carbonyl compounds. The keto form predominates, and most of the reactions of cyanuric acid have their counterparts in the chemistry of the cyclic imides. Many of the reactions involve the replacement of all three imido hydrogens (Scheme 31). Usually, the reaction cannot be controlled to produce the mono- or di-substituted isocyanurates specificially, but there are exceptions, e.g. the reaction between cyanuric acid and aziridine (Scheme 31) (B-79MI22001, 63JOC85, 63AHC(2)245). 

Reaction with Carbon Nucleophiles. Unactivated aziridines react with the lithium salts of malonates or p-keto esters in the presence of lithium salts to yield 3-substituted pyrrolidinones (56—59), where R = alkyl and aryl, and R = alkoxyl, alkyl, and aryl. 

Terminal epoxides of high enantiopurity are among the most important chiral building blocks in enantioselective synthesis, because they are easily opened through nucleophilic substitution reactions. Furthermore, this procedure can be scaled to industrial levels with low catalyst loading. Chiral metal salen complexes have also been successfully applied to the asymmetric hydroxylation of C H bonds, asymmetric oxidation of sulfides, asymmetric aziridination of alkenes, and the asymmetric alkylation of keto esters to name a few. 

Oxaziridines are converted to ring-expanded lactams under photochemical conditions. A-Tosyl aziridines with an a-hydroxyalkyl substituent give a pinacol rearrangement product in the presence of Lewis acids, such as Sml2> in this case a keto-A-tosyl amide. ... 

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