Aziridines, reaction with acid enolates

An alternative route starting from serine 73 or threonine 68 74 makes use of diethoxy-triphenylphosphorane. Attempts to asymmetrically synthesize (25)-aziridine-2-carboxylic acid (1) by treating a, 3-dibromopropanoates with chiral amines 75 or by the Staudinger reaction from oxirane-2-carboxylic acid ester 70,76 leads to optically impure products, whereas 3-alkyl derivatives of tert-butyl aziridine-2-carboxylates can be prepared with high cis-selectivity from a-halo ester enolates and jV-trimethylsilyl imines. 77 Moreover, when optically... 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Sodium enolates of ketones and disodium enediolates of substituted phenylacetic acids reacted with activated aziridines to afford 7-amido ketones and 7-amidobutyric acids, respectively (Scheme 72). Aziridine-2-carboxylic acid esters can be utilized as versatile precursors for amino acid derivatives. Although the product distribution resulting from the reaction of activated aziridine-2-carboxylates with amines depends on the structure of the reactants, the reactions with alcohols or thiols in the presence of acidic cabilysts generally gave the a-amino acid derivatives (Scheme 73). ° On the other hand, free 3-methyl-2-aziridinecarboxylic acids (168) reacted with thiophenol, cysteine and glutathione to afford P-amino acid derivatives with sulfur substituents at the a-position as the main product (Scheme 73). ... 

In a similar vein, Davis and co-workers have found the p-toluenesulf nyl group to be useful for such purposes. Aziridine-2-carboxylic acid derivatives 138 are prepared in high diastereomeric purity by a Darzens-type reaction of the lithium enolate of methyl bromoacetate (137) with enantiopure sulfrnimines (e.g., 136) [94JOC3243]. These compounds have been employed as intermediates in the asymmetric synthesis of the antibiotic (+)-thiamphenicol (139) [94TL7525]. 

Different from their previous reports, Hashimoto and co-workers developed a novel reaction in 2009. They found that allylic C—H bond amina-tion reaction occurs when silyl enol ether 120 derived from cyclohexanone is used. This interesting insertion reaction is ascribed to the fact that silyl enol ether 120 can just be -shaped. On the other hand, when Z-shaped silyl enol ethers 118 were employed (Scheme 1.43, top), the aziridination reactions occurred under similar conditions. After treating with trifluoroacetic acid, the a-aminated carbonyl products 119 were obtained in high levels of enan-tioselectivity. Starting from the p-aminated carbonyl compound 121, they accomplished the formal synthesis of (-)-pancracine (Scheme 1.43, bottom). 

Through the ester enolate-imine route, we have been able to prepare with high diastereo-and enantio-selectivity carbapenems such as PS-5 and PS-6 as well as ip-methyl carbapenems and monobactams. A promising application is represented by the stereospecific synthesis of chiral aziridines, potential starting materials for the preparation of a- and P-amino acids. Metallo imines also undergo reaction with a number of organometallic compounds to give primary amines and chiral 1,2-aminols. 

Keto-acids.—The generation and reactions of dianions (7) have been reported. These react very efficiently with alkylating agents (even cyclohexyl tosylate affords a 64% yield of the expected adduct) to give a-keto-acid derivatives. Treatment of (7) with epoxides leads to butyrolactones and with aziridines to y-amino-a-keto-acid derivatives (see also ref. 77a). A simple looking route to /8-keto-acids (9) is by condensation between an acid chloride and the enolate of... 

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