Bromoallylation

N-(2-Bromoallyl)-ethylamine with sodium amide in liquid ammonia gave N-ethylallenimine (154) by either of the paths shown (116,117). 

Cyclopropyl-l,5-benzodiazepin-2-ones 4 are converted into 3-chloro derivatives 5 by the action of, V-chlorosuccinimide in contrast, A-bromosuccinimide provides 4-(l -bromoallyl)bcnzo-diazepinones 6 with opening of the cyclopropane ring.269... 

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). 

Reaction of N-(2-bromoallyl)-N-prop-2-ynylamines 72 with tert-butyllithium, followed by reaction with zirconocene methyl chloride and subsequent cyclization gives 1,1-lithio-zirconioalkenes 73 via 74 and intermediate 75 (Scheme 7.23) [144,145], Treatment of the lithiozirconium complex 73 with deuterated sulfuric acid leads to the trideuterated pyrrolidine 76. 

The reported boiling point of N-(2-bromoallyl)ethylamine is 148-153°. It is strongly recommended that the product and other 2-haloallylamines be distilled at reduced pressure under nitrogen, for the submitters have noted two instances when a 2-haloallylamine polymerized with considerable evolution of heat during slow distillation at atmospheric pressure. 

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... 

The method described is essentially that of Pollard and Par-cell.4 N-Ethylallenimine has been prepared by treating N-(2-bromoallyl)ethylamine in liquid ammonia with sodium amide,4-6 lithium amide,6 or potassium amide.6... 

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. 

Table 1. Preparation of 4-functionalized indole derivatives 2 and 3 from N-(2-bromoallyl)-2-fluoroanilines (1).

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.

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 %)... 

Bromoallyl 2-fluorophenyl thioether (22b) 2-Fluorothiophenol (1.3 g, 10 mmol) was treated with K2C03 (1.5 g, 11 mmol). 2,3-Dibromopropene... 

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]. 

The submitters obtained 11.6 g (72%) of product starting from 18.4 g of (2-bromoallyl)diisopropoxyborane and 10.7 g of ethyl levulinate. The checkers obtained yields of 65-69% in runs on several different scales. 

SYNTHESIS OF 4-(2-BROMO-2-PROPENYL)-4-METHYL-y-BUTYROLACTONE BY THE REACTION OF ETHYL LEVULINATE WITH (2-BROMOALLYL)DIISOPROPOXYBORANE PREPARED BY HALOBORATION OF ALLENE... 

A. (2-Bromoallyl)diisopropoxyborane. A flame-dried, 200-mL, three-necked, round-bottomed flask is equipped with a magnetic stirring bar, rubber septum, 125-mL... 

The checkers found that the 1H NMR spectrum of (2-bromoallyl)-diisopropoxyborane is concentration dependent. When the NMR spectrum was measured at a concentration of 20 pL of product in ca. 0.5 mL of CDCI3, (2-bromo-allyl)diisopropoxyborane was observed along with a substantial amount of a second material that had 1H resonances for the vinylic and allylic protons that were very similar in chemical shift to the vinylic and allylic resonances of the desired product. However, when the 1H NMR spectrum of a much more concentrated solution (ca. 250... 

Although (2-bromoallyl)diisopropoxyborane can be stored under nitrogen in a refrigerator for a few months, it is recommended that the reagent be redistilled if stored fora longer time. 

A useful and practical version of the above protocol involves a catalytic process in which the enone, a bromoallyl silane, cesium carbonate and diisobutyl teUuride react in a one-pot procedure to give the desired cyclopropanes with a high cw-stereoselectivity. 

Cyclic thioureas such as 2-thiouracil 1118 (R = H), its 6-methyl 1118 (R = Me) and 6-propyl derivatives 1118 (R = Pr), as well as thiobarbital 1119 are effective agents against hyperthyroidism, while thiamylal 1120 is used as an anesthetic. A large number of barbituric acid derivatives have hypnotic or sedative effects, and allobarbital 1121 (R = R = allyl), aprobarbital 1121 (R = allyl, R = r-Pr), cyclobarbital 1121 (R = Et, R = 1-cyclohexenyl), pentobarbital 1121 (R = Et, R = 2-pentyl), phenobarbital 1121 (R = Et, R = Ph), propallyonal 1121 (R = isopropyl, R = 2-bromoallyl), and secobarbital 1121 (R = allyl, R = 2-pentyl) are all examples of N-unsubstituted barbiturates, while hexobarbital 1122 represents an N-methylated derivative. 

Bromoallyl)cyclobutanones rearranged to give bicyclo[4.1.0]heptan-3-ones 7 and 8 on reduction with tributyltin hydride.119... 

We note that in this case the elimination products, that is, 2-bromo-3-chloropropene (BCP) and 2,3-dibromopropene (DBP), are allylic halides. Consequently, these both hydrolyze in relatively fast steps most likely via SN1 reactions (see the example given in Table 13.6) to form 2-bromoallyl alcohol (BAA). 

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