Allylic bromides, improved preparation

Two papers 5 have appeared recently aiming at the improvement of the preparation of ethyl bromide. Although the preparation of allyl bromide was studied as recently as 1913, yields of only 60-8 5 per cent are reported by Claisen and Eisleb.6... 

Reactions with —OH Groups and Epoxides.—The formation of A -l,2-oxaphos-pholen derivatives from propargylic alcohols and phosphorus trichloride has been studied in detail. Intermediate phosphites (24) and allenic phosphonates (25) are described, and the A -l,2-oxaphosphoIen is produced in the final stage, as shown. Improved conditions have been outlined for the preparation of allylic bromides (26) from allylic alcohols and phosphorus tribromide. Related reactions of primary alcohols with the complex of phosphorus trichloride and DMF lead to the chloride (27) 22 addition of zinc bromide to the reaction results in the formation of alkyl bromides, but an attempt to extend this exchange to the preparation of cyanides was not successful. ... 

Small amounts of water act in synergy with sonication and solid-support catalysis, for instance, in the reaction of thiocyanate ions. As in the previous case, presonication of the reagent and the support was found to improve the selectivity. These methods permit the substitution reactions to be run even in apolar solvents. Two practically simultaneous papers have described the preparation of aryl sulfones by alkylation of sodium arylsulfinates with reactive alkyl chlorides.i The reaction with benzyl chlorides is best performed on alumina, and allyl bromide reacts quantitatively in a DMF-water mixture in a few minutes. Activated primary halides undergo substitution by sodium azide in aqueous solution to give the potentially explosive organic azides. 1 The paper discusses the possible role of the relative densities of the starting material, the aqueous solution of the reagent, and the product in the success of the preparation. 

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

Bodroux 4 has prepared allyl, propyl, and isobutyl bromides by means of a modified Norris method. Bromine was reduced by means of sulfur dioxide, the alcohol was added and the mixture distilled. The yields were not the highest, however. The method described above is an improvement of the Norris-Bodroux method. Two essential modifications consist in the addition of concentrated sulfuric acid, and in the recommendation of a refluxing period preliminary to the distillation. The sodium bromide method has been improved by the introduction of similar modifications. 

The addition of lithiimi 1-oxyalkanides 26a to the carbonyl group of aldehydes and ketones usually takes place with very low enantiofacial differentiation, giving rise to mixtures of (half-protected) syn- and awfi-diols 27 [Eq. (lOa)j [16,17]. A slight improvement is achieved in the presence of magnesium bromide [17]. Even the strained lithium compound 29, bearing a lactone moiety, could be prepared via lithiodestannylation of 28 and was added onto the enal 30 to give the allylic alcohol 31 during the synthesis of the taxol ABC system [Eq. (lOb)] [18]. 

Full details are now available of Torssell s synthesis of l-desoxylycorin-7-one (15) (cf. Vol. 5, p. 172). ° Application of the phenylselenium bromide procedure to the lactam (12) led to an improved synthesis of the enol (13), which by acid-catalysed allylic rearrangement was converted into the allylic acetate (14) (Scheme 1) lycorine (16) has already been prepared from the latter compound. 

One obvious method for the preparation of NCAs is of course by cyclization of AT-alkoxycarbonyl amino acid chlorides, as originally discovered by Leuchs (eq. 1) (1). Over the years, various improvements of this so-called Leuchs method have been made. While the original procedure used thionylchloride for the chlorination of AT-alkoxycarbonyl a-amino acids, it was foimd that phosphorus bromide is more convenient, allowing cyclization to take place at lower temperatures (4). The rate of cyclization depends on the nature of the alkoxycarbonyl group and decreases in the following order ethyl < methyl < allyl < benzyl. Equation 1 shows a mechanism that is in line with these observations. 

Greaney et al. introduced the Heck reaction to the benzyne three-component coupling to prepare 1,2-functional-ized arenes 28 and 29. Alternatives to allyl chlorides as the initial carbopalladation electrophile were presented, that is, methyl bromoacetate and benzyl bromides, thus avoiding the formation of benzyne/benzyne/allyl by-products and therefore improving the efficiency of the reaction [39], When using aryl iodides as the electrophilic partners, highly functionalized biaryl compounds 30 are obtained (Scheme 3.20) [40]. 

---