Acetoxy bromides

OPTICALLY ACTIVE EPOXIDES FROM VICINAL DIOLS VIA VICINAL ACETOXY BROMIDES THE ENANTIOMERIC METHYLOXIRANES... 

If desired, glycidic esters can be derived from a,3-dihydroxy esters, such as (110), by either of two methods. In one method, reaction of the diol with an arenesulfonyl chloride is regioselective, producing the a-arenesulfonate (111) in preference to the 3-sulfbnate. Treatment of (111) with an equivalent of base produces the erythro-glycidic ester (112) in good yield. In the second method, the diol is converted to a bromohydrin (114) via the acetoxy bromide (113). The brotmhydrin (114) affords the threo-g ycidic ester (115) on exposure to potassium caitxHiate in methanol. 

Knecht, M., Boland, W. (E)-Selective alkylidenation of aldehydes with reagents derived from a-acetoxy bromides, zinc and chromium trichloride. Syn/ett 1993, 837-838. 

E)-Alkenes. Condensation of a-acetoxy bromides with aldehydes by CrCl j-Zn leads to (E)-alkenes. In the synthetic sense this method is complementary to the Wittig reaction. 

Similarly, treatment of 889 with 4 equivalents of saturated HBr in acetic acid affords acetoxy bromide 893. Debromination with a mixture of trimethyltin chloride, AIBN, and sodium borohydride (in situ generation of trimethyltin hydride) furnishes 892, which under acidic hydrolysis gives 203. The overall yield of 203 from 889 is 56% when the process is carried out on a 0.2-mol scale [198]. 

Takai and Utimoto showed that reactions of aldehydes and a gem-diiodoalkane with chromium(II) chloride gave Wittig-type olefination products (Scheme 5.25) [35]. The notable points of this transformation are stereoselective ( )-alkene formation and chemoselective reaction with the aldehyde. Ketones are recovered unchanged. Instead of a gem-diiodoalkane, a-acetoxy bromide can also be used for this transformation [36]. 

Conversion to a more facile, sulfur-derived, leaving group can be achieved by treatment with sodium thiosulfate or salts of thio and dithio acids (75,87). Under anhydrous conditions, boron tribromide converts the 3 -acetoxy group to a bromide whereas trimethyl silyl iodide gives good yields of the 3 -iodide (87,171,172). These 3 -halides are much more reactive, even when the carboxyl group is esterified, and can be displaced readily by cyano and by oxygen nucleophiles (127). 

It has been reported recently that 17/ -acetoxy-5a,14a-androstan epimerizes at C-14 when photolyzed in cyclohexane solution in the presence of mercuric bromide. When the reaction is carried out in perdeuterated cyclohexane, the product consists of 55 % d - and 12% d2-labeled species. This reaction may develop into an interesting deuteration technique if the incorporated deuterium can be securely assigned to the epimerized position. 

Reaction of 17j -acetoxy-3,3-ethylenedioxy-5a-androstan-l-one (1) with methylmagnesium bromide followed by treatment with acid and reacetylation affords the 1-methyl-A -3-ketone (3). The configuration of carbon-1 of the intermediate (2) has not been established/ ... 

Addition of methylmagnesium bromide or methyllithium to 21-acetoxy-3,3 20,20-bisethylenedioxy-17a-hydroxypregn-5-ene-7,l 1-dione and subsequent acid treatment affords 7-methyl-A -cortisone. ... 

The addition of methylmagnesium bromide to 3j -acetoxy-D-homo-androst-5-en-17a-one (52) proceeds with formation of the equatorial 17a/5-methyl carbinol (53), a result which is analogous to the previously described alkylations of 12-keto steroids. 

Ethynylation of 3j -hydroxy-16a-methyl-5a-androstan-17-one in a mixture of diethylene glycol dimethyl ether and diethylene glycol monoethyl ether in the presence of potassium hydroxide produces two isomeric 17-ethynyl derivatives. This result is not unexpected since molecular models suggest that the steric influence of the 13/ -methyl group is nearly offset by the 16a-methyl group. The presence of a 16a-acetoxy group in the estrone series also leads to the formation of epimeric 17-ethynyl compounds (61) and (62) on reaction with acetylenedimagnesium bromide. 

The C-20 epimeric diacetates (69) and (70) are obtained in a total yield of 30% by acetylation of the mixture formed from 21-acetoxy-3j -hydroxy-pregn-5-en-20-one (68) with methylmagnesium bromide. ... 

A solution of 6.3 g (0.9 moles) ethoxyacetylene in 50 ml ether is added dropwise during 30 min to a Grignard reagent prepared from 2.18 g (90 mg-atoms) magnesium and 9.81 g (90 mmoles) ethyl bromide. The reaction mixture is stirred for 1 hr at room temperature and then a solution of 3 g (9 mmoles) 3) -acetoxyandrost-5-en-I7-one in 50 ml dry ether is added dropwise. The mixture is refluxed for 1 hr and after cooling to 0° poured into 100 ml of an aqueous ammonium chloride solution. The aqueous solution is extracted with ether, and the organic extract is washed with ammonium chloride solution and water, dried, and evaporated. The residue is chromatographed on 130 g alumina (activity III). Elution with petroleum ether-benzene (1 1) yields, after crystallization from acetone-hexane, 1.27 g (35%) 3j5-acetoxy-17a-ethoxyethynylandrost-5-en-17) -ol mp 138-139° Ho -122°. 

Ethoxyacetylene, 74, 136, 138, 181 1 -Ethoxycyclohepta-1,3,5-triene, 365 1-Ethoxycyclohexene, 365 1 - Ethoxy-7,7-dichloronorcarane, 365 17a-Ethoxyethynylandrost-5-ene-3, 17 -diol 3-acetate, 181, 182 Ethoxyethynylmagnesium bromide, 138 21 -Ethoxy-3-methoxy-19-norpregna-1,3,5(10) -trien-20-yne-17 -oI, 139 Ethyl 3 -acetoxy-17/3-hydroxy-17 a-pregn-5-en-21-oate, 139... 

J/3,5a,6(3- Trihydroxy-6oi, 17a-Dimethyl-17 -Carbometboxyandrostane (IV) 3(3-Acetoxy-5a-hydroxy-17a-methyl-17/3-carbomethoxyandrostan-6-one (III, 1.004 g) is dissolved in dry benzene (25 ml) and methyl magnesium bromide solution in ether (3M, 10 ml) is added. 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

The acetoxy group is introduced exclusively at the benzylic carbon. This is in accord with the intermediate being a weakly bridged species or a benzylic cation. The addition of bromide salts to the reaction mixture diminishes the amount of acetoxy compound formed by shifting the competition for the electrophile in favor of the bromide ion. Chlorination in nucleophilic solvents can also lead to solvent incorporation, as, for example, in the chlorination of 1-phenylpropene in methanol.37... 

Otera et al. extended the tin-mediated allylation to 2-substituted allyl bromides.80 When 2-bromo and 2-acetoxy-3-bromo-l-propene were used, the allylation with tin produced the corresponding functionalized coupling products (Eqs. 8.36 and 8.37). In the case of 2,3-dibromopropene, the reaction occurred exclusively through allylation in the presence of the vinyl bromo group. The presence of other electrophiles such as a nitrile (-CN) or an ester (-COOR) did not interfere with the reaction. 

---