Enolates reaction with aziridines

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

A chiral enolate derived from a bromoacetyl camphor sultam [(52) in turn prepared from Oppolzer s sultam63a b] undergoes an aza-Darzens reaction with modified amines to produce aziridme derivatives in high de.11 Cleavage yields aziridine carboxylates. 

The nitrido complex was applied to the direct asymmetric animation with a silyl enol ether as a substrate. Although several examples for achiral aminations of silyl enol ethers have been reported [32], an asymmetric version of reagent-controlled reaction has not appeared except for the one recent example [33] and the diastereoselective reactions with silyl enol ethers having a chiral auxiliary [34], The amination, which is presumed to take place via an aziridine intermediate [5g, lid,32], proceeded smoothly to give the A-tosylated a-aminoketone in 76% yield with 48% ee. When the same silyl enol ether was treated with complex 15 under Carreira s condition, the TV-trifluoroacetylated a-aminoketone was obtained in 58 % yield with 79 % ee (Scheme 24). 

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). ... 

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... 

Stamm and his co-workers have shown that pyrrolidones can be obtained from aziridines by reaction with sodium enolates of simple esters, and if or R = H in (99), then further amidoethylation can result. 

Other Electrophiles. In addition to carbonyl compounds, ester enolate (1) also reacts with other electrophiles. With nitrones, the product is dependent upon the structure of the nitrone a,N-dialkyl nitrones provide alkenes, while a-aryl-A-alkyl nitrones or aW-diaryl nitrones usually give aziridines. With the phenylhy-drazone of a 1,2-dicarbonyl compound, reaction with (1) provides a convenient preparation of 3(2f/)-P3 dazinones (eq 3). ... 

The Darzens condensation reaction has been used with a wide variety of enolate equivalents that have been covered elsewhere. A recent application of this important reaction was appljed toward the asymmetric synthesis of aziridine phosphonates by Davis and coworkers.In this application, a THF solution of sulfinimine 34 (0.37 mmol, >98% ee) and iodophosphonate 35 (0.74 mmol) was treated with LiHMDS (0.74 mmol) at -78 °C to give aziridine 36 in 75% yield. Treatment of 36 with MeMgBr removed the sulfinyl group to provide aziridine 37 in 72% yield. 

More recently, Davis and co-workers developed a new method for the asymmetric syntheses of aziridine-2-carboxylates through the use of an aza-Darzens-type reaction between sulfinimines (N-sulfinyl imines) and a-haloenolates [62-66]. The reaction is highly efficient, affording cis- N-sulfmylaziridine-2-carboxylic esters in high yield and diastereoselectivity. This method has been used to prepare a variety of aziridines with diverse ring and nitrogen substituents. As an example, treatment of sulfinimine (Ss)-55 (Scheme 3.18) with the lithium enolate of tert-butyl bromoacetate gave aziridine 56 in 82% isolated yield [66],... 

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... 

Recent progress on the use of hypervalent iodine reagents for the construction of carbon-het-eroatom (N, O, P, S, Se, Te, X) bonds is reviewed. Reactions of aryl-A3-iodanes with organic substrates are considered first and are loosely organized by functional group, separate sections being devoted to carbon-azide and carbon-fluorine bond formation. Arylations and alkenyla-tions of nucleophilic species with diaryliodonium and alkenyl(aryl)iodonium salts, and a variety of transformations of alkynyl(aryl)iodonium salts with heteroatom nucleophiles are then detailed. Finally, the use of sulfonyliminoiodanes as aziridination and amidation reagents, and reactions of iodonium enolates formally derived from monoketones are summarized. 

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