Haloamidation, alkene

Currently the most popular of the pseudohalides are N-haloamides. These reagents are used in conjunction with the solvent or an added nucleophilic reagent to give overall 1,2-addition of a halogen and a nucleophile to the alkenic substrate. The amides of choice seem to be N-halosuccinimides. The low nu-cleophilicity of the succinimdyl anion allows for a variety of nucleophiles to attack the initially formed halonium ion. 

A general process for haloamidation of alkenes has been developed, which is characterized by the addition of a bromine atom and an amide nitrogen in an anti sense to the olefinic double bond [(7) - (8)]. The process involves the use of an A-bromoamide and a Lewis acid as a source of Br+, which reacts with the alkene. The amide group is derived from a nitrile and a water molecule, which serve as nucleophiles for the overall three-component reaction. The reaction has been shown to be general for a broad range of alkenes and nitriles an analogous chloroamidation reaction has also been demonstrated 25... 

The nitrogen source for the aziridination of alkenes, a nitrene or nitrenoid, can be generated in various ways (1) oxidation of a primary amine (2) base-induced -elimination of HX from an amine or amide with an electronegative atom X (X = halogen, O) attached to the NH group or by -elimination of metal halides from metal A-arenesulfonyl-A-haloamides (3) metal-catalyzed reaction of [A-(alkane/arenesulfonyl)imino]aryliodanes (4) thermolytic or photolytic decomposition of organyl azides and (5) thermally induced cycloreversion reactions . 

Other compounds prepared by halolactamization of alkenes (and preceding the above woik ) include (64),(65), (66),2 (67), (bS), (69) and (70). Note that related sulfeno-, seleno- and tellu-ro-cyclizations have been discussed earlier (Section 3.5.5). Finally, related products may be obtained by radical reactions of N-haloamides, giving the following (71-73) representative products in reactions promoted thermally (71),photochemically (72 and 73),279.2so dibenzoyl peroxide (73) ° or chro-mous chloride (73). ... 

Furthermore, /i-haloamides 14 were obtained in low yield by reaction of nitriles with alkenes in the presence of chlorine or bromine. The tram addition led first to imino intermediate 13 which, depending on the reaction conditions, was converted into a number of heterocyclic compounds179-181. 

An alternative addition at 0 °C of an alkene to bromine in the presence of silver perchlorate in acetonitrile, followed by basic hydrolysis, afforded /7-haloamides, e.g., 14, in good yield. The stereochemistry of the product was confirmed on comparison with known compounds41 -43 182. 

V-Haloamides such as 76 are reductively cleaved (2 F) to give an anion by loss of a halide ion coupling takes place when an excess of an activated alkene is added, as in Eq. (31) [189]. 

They can be prepared from acyclic compounds. In an industrial process, dimethyl malonate is condensed with 4-alken-3-ones (or a mixture of the respective ketones with 5-chloroalkan-3-ones) to give a substituted 3-hydroxy-2-cyclohexenone. Aro-matization, in good yield is achieved by reaction of the hydroxycyclohexenones with a suitable /V-haloamide. The intermediate 3-hydroxy-2-cyclohexenones can also be obtained by condensation of methyl 3-oxoalkanoate with methyl crotonate [182]. 

The tributyltin hydride-mediated carbon-carbon bond formation via radical addition and cyclization of alkyl halides with alkenes has often been a choice for construction of various organic molecules [1], However, the requirement for high-temperature initiators or photo initiation and the difficulties associated with purification of the products from tributyltin halides tend to limit the widespread use of these methods, despite the efforts to make the methods easier [Ic, 2], Recently, nickel-mediated radical additions and cyclizations have been introduced as promising alternatives to the tributyltin hydride methods. These are the nickel powder-acetic acid method for cyclization of haloamides to y-lactams, y -lactams and in-dolones, the borohydride exchange resin-nickel boride method for radical addition, nickel-catalyzed electroreductive cyclization and nickel-catalyzed Kharasch addition of polyhalo compounds. 

The principal product from irradiation of quinoline-2-carbonitrile in propan-2-ol-aqueous HCl is the radical-derived dimer (225). The factors influencing the photoaddition of iV-haloamides to alkenes have been examined/ and full details... 

Chlorination of Alkenes and Alkynes. The haloamidation of olefins was carried out by reaction of Af-haloimides (X = Cl, Br) with nitriles in the presence of Lewis acids. It was presumed that the reaction involves nucleophilic attack of nitrile on the halonium ion followed by hydrolysis of the products (eq 38). ... 

Haloamidation of simple alkenes with A-halophthalimide, catalysed by AgBF4 or InBr3/AgBF4 (1 3), has been developed and shown to proceed with high regio-and diastereo-selectivity. A related bromoamidation was attained with a mixture of Bu OCONHBr and Bu OCONH2- An enantioselective version has been developed for... 

The common methods for the S5mthesis of p-lactams are cycloaddition reactions such as the Staudinger s ketene-imine cycloadditions, ester enolate-imine cycloadditions, alkyne-nitrone cycloadditions (Kinugasa reaction), alkene-isocyanate cycloadditions, and Torii s cyclocarbonylation of allyl halides with imines. Several cyclizahon reactions of p-amino esters, p-amino acids, p-hydroxamate esters, and a-diazocarbonyls have been developed for the formation of p-lactam ring. N,N-Disubstituted a-haloamides cyclize by C3-C4 bond formation leading to the formation of P-lactam ring. 

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