N-haloamides

A similar reaction has been carried out on N-haloamides, which give -lactone. 

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. N. Mirskova,T. I. Drozdova, G. G. Levkovskaya, M. G. Voronkov, Reactions of N-chloramines and N-haloamides with unsaturated compounds, Russ. Chem. Rev. 1989, 58, 250-271. 

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). ... 

Selective oxidation of a primary alcohol. The final step in a recent synthesis of strophanthidin required selective oxidation of the primary hydroxyl group of stro-phanthidol (1) to an aldehyde group. Oxidations with chromic acid, N-haloamides,... 

Isocyanates were prepared in high yield from N-haloamides 180 with DBU in dimethylformamide (79JAP(K)128521). 

Step (1) is the halogenation of an amide. This is a known reaction, an N-haloamide being isolated if no base is present. Furthermore, if the N-haloamide isolated in this way is then treated with base, it is converted into the amine. 

Neale, R. S. Nitrogen radicals as synthesis intermediates. N-Haloamide rearrangements and additions to unsaturated hydrocarbons. Synthes/s 1971, 1-15. 

N-Chlorocarbamate/Chromium(II) Chloride. Enol ethers (see Eq. 80) and glycals (see Eq. 84) react with N-chlorocarbamates in the presence of chromous chloride to produce a-amino carbonyl derivatives.343 Trimethylsilyl enol ethers give low yields because of their ease of hydrolysis. A radical chain mechanism has been proposed with the N-haloamide acting as the transfer agent (Eq. 32).344... 

Oxidations.1 The reagent compares favorably with N-haloamides and chromic acid for oxidation of secondary alcohols. Cyclohexanol is oxidized to cyclohexanone in 90-95% yield at room temperature. Less easily oxidized alcohols may require higher temperatures to initiate the free-radical reaction. The oxidation may become too vigorous if cooling is insufficient or if run on a large scale. 

Now what There s no hydrogen on the N anymore, so how can you get to an intermediate N-haloamidate that can decompose to the necessary acyl nitrene ... 

Sharpless catalytic asymmetric aminohydroxylation (AA) provides a direct and efficient route to the taxol side chain as well as a number of other natural products and synthetic ligands. The required asymmetry of the taxol side chain was controlled by (DHQ)2-PHAL, and hydroxyla-tion was achieved with potassium osmate (K20s02(0H)4). Various N-haloamide salts were investigated, and yields and percentage ee were good to excellent under different conditions. For example, reaction of methyl cinnamate under Sharpless catalytic AA conditions gave (2R,3S) N-tosyl-3-phenyl isoserine 7.3.1 in 82% ee in 69% yield. Compound 7.3.1 was then converted to the taxol side chain acid in two steps in good yield (262). 

Investigation of the behavior of this and other N-haloamides showed that they react with alkali to give unstable salts. ... 

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