Bromoallyl ethers

Scheme 6. Attempted anionic cyclization of 2-bromoallyl ether and thioether 22. i) /BuLi (3.5 equiv), THF, -110°C ii) -110 20°C iii) H20, 20 °C.

In a subsequent study, the impact of replacing one or both of the amide bonds with either a diacylhydrazine or a 1,3,4-oxadiazole was explored [36]. (fi)-Bromoallyl ethers were employed in the PI and Pi positions and similarly subjected to Suzuki conditions using the two aryl boronic acids that gave the most potent inhibitors in the previous study. Potent plasmepsin inhibitors were produced however, no real improvements in activity compared to the parent compound were observed (Scheme 5). The use of the preligand, [(f-Bu3)PH]BF4 [37], in combination with barium hydroxide was found beneficial although the yields were very low in these reactions. 

A highly efficient cascade reaction of propargyl 2-bromoallyl ethers with a tethered 3-oxoalkyne has been described to give efficient access to tricyclic [c]-annulated furans <2007JOC1395>. [f]-Annulated furans have also been made... 

As a related reaction, Rawal carried out intramolecular vinylation of 2-bromoallyl ether of electron-rich resorcinol 72 and obtained the benzofurans 73 and 74 in equal amounts by ortho and para substitutions when the Herrmann catalyst (XVIII-1) was used. Cleavage of the allyl ether to give resorcinol (75) is a side reaction, whose amount increases when Pd(PPh3)4 is used as a catalyst. Similarly the indoles 77 and 78 were synthesized in 1 1 ratio from 76 [19]. 

The two-phase mixture is placed in a separatory funnel, and the heavy red-brown oil is separated. The aqueous phase is extracted with 100 ml. of ether. The oil and the ether extract are combined, washed with 50 ml. of saturated sodium chloride, and dried over potassium carbonate. The drying agent is removed by filtration, and the filtrate is distilled. Colorless 2-bromoallyl-amine is collected at 65-68°/100 mm. weight 49-59 g. (59-72%) 1.5075-1.5085 (Note 6). 

This method is essentially that described by Pollard and Par-cell.8 No other procedure appears to have been used to prepare N-(2-bromoallyl)ethylamine. A number of N-(2-haIoaIIyl)alkyl-amines have been prepared by treatment of a 2,3-dihalopropene with a primary alkylamine in water,8-4 ether,8-4 or benzene.5... 

Gronowitz adapted this technology to one-pot syntheses of indole-3-acetic acids and indole-3-pyruvic acid oxime ethers from A-BOC protected o-iodoanilines [328, 329]. Rawal employed the Pd-catalyzed cyclization of A-(o-bromoallyl)anilines to afford 4- and 6-hydroxyindoles, and a 4,6-dihydroxyindole [330], and Yang and co-workers have used a similar cyclization to prepare 8-carbolines 287 and 288 as illustrated by the two examples shown [331]. The apparent extraneous methyl group in 288 is derived from triethylamine. 

Bromoallyl 2-fluorophenyl ether (22 a) 2-Fluorophenol (2.2 g, 20 mmol) was treated with K2C03 (3.0 g, 22 mmol). 2,3-Dibromopropene (4.0 g, 20 mmol) was added and the mixture was heated at reflux overnight. Workup according to the general procedure above gave 22 a (3.68 g, 80 %)... 

The bromination of phenyl-1,2-propadiene in MeOH at 0 °C led to a regioisomeric mixture of 2-bromoallylic methyl ethers 17 and 18 with the product 17, in which the methoxy group was attached to the bcnzylic position, being the major route (Scheme 10.15) [16]. 

Diels-Alder reaction with cyclopentadienes. An improved synthesis of a key intermediate (6) to gibberellic acid (7) begins with the cycloaddition of 1 to a 2 1 mixture of 2- and l-(2-bromoallyl)cyclopentadiene (2) to give the adduct 3 in which the acetyl group has the enr/o-orientation. The silyl enol ether of 3 when heated undergoes a Cope rearrangement to give a eis-hydrindene (4), which was converted... 

A mixture of N-(2 -bromoallyl)-3-hydroxy-4-(p-tolyl) pyridinium bromide hydro-quinone (lOOmg) dissolved in ethyl acrylate were heated 1.5 hours, (27mmol), 7.5 ml TEA and cooled, and diluted with 200 ml diethyl ether. The suspension was filtered and the product isolated by chromatography using hexanes/EtOAc, 4 1, in 52% yield. H-NMR data supplied. 

This reagent can be prepared by reaction of 2-bromoallyl alcohol in ether with 2.5 eq. of f-butyUithium at -78 to 0°. It reacts with carbonyl compounds to form, after hydrolysis, unsaturated diols of type (1) in 65-75% yield. ... 

---