Bromides, preparation from epoxides

To a mixture of 100 ml of THF and 0.10 mol of the epoxide (note 1) was added 0.5 g Of copper(I) bromide. A solution of phenylmagnesium bromide (prepared from 0.18 mol of bromobenzene, see Chapter II, Exp. 5) in 130 ml of THF was added drop-wise in 20 min at 20-30°C. After an additional 30 min the black reaction mixture was hydrolysed with a solution of 2 g of NaCN or KCN and 20 g of ammonium chloride in 150 ml of water. The aqueous layer was extracted three times with diethyl ether. The combined organic solutions were washed with water and dried over magnesium sulfate. The residue obtained after concentration of the solution in a water-pump vacuum was distilled through a short column, giving the allenic alcohol, b.p. 100°C/0.2 mmHg, n. 1.5705, in 75% yield. 

Medroxyprogesterone acetate (74) is stmcturaHy related to and has been prepared from hydroxyprogesterone (39) (Fig. 10). Formation of the bis-ketal accomplishes the protection of the ketones and the required migration of the double bond. Epoxidation with peracetic acid produces a mixture of epoxides (75), with a predominating. Treatment of the a-epoxide with methyl magnesium bromide results in diaxial opening of the epoxide. Deprotection of the ketones provides (76), which is dehydrated to (77) by treatment with dilute sodium hydroxide in pyridine. Upon treatment with gaseous hydrochloric... 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

Under non-aqueous conditions the epoxy function in the epoxylactones can be opened only by Lewis acid assistance. Thus, 2-fluoro-2-deoxy-lactones have been prepared from 2,3-epoxylactones by treatment with HF-amine complexes [38,49,50], while 5,6-epoxylactones yield 6-deoxy-6-fluoro-lactones by this treatment [49, 50]. Likewise, BFj-assisted opening of a 2,3- epoxy function with TMSN3 [51] gave a 2-azido-2-deoxy-lactone [52]. In all cases the opening of the epoxide is a frans-opening, and it is noteworthy that under acidic conditions the nucleophile attacks at C-2 or at the primary position, similar to the opening of acetoxonium ions by bromide ions in the... 

Fig (20) Bromide (172), prepared from alcohol (171) on alkylation yields (173) which is converted to (174) without any difficulty. Conversion of (174) to homoallylic bromide (175) is accomplished by the method of Julia. On alkylation followed by cyclization generated the tricyclic alcohol which undergoes dehydration to yield unsaturated ester (177) which is converted to unsaturated lactone (146) by epoxidation and elimination. 

An interesting reagent is Li2NiBr4, prepared from anhydrous lithium bromide and nickel(II) bromide. It reacts with epoxides regio- and stereoselectively (equation 182)1121. 

Alkyl halides (particularly bromides) undergo oxidative addition with activated copper powder, prepared from Cu(I) salts with lithium naphthalenide, to give alkylcopper species10. The alkyl halides may be functionalized with ester, nitrile and chloro functions ketone and epoxide functions may also be tolerated in some cases11. The resulting alkylcopper species have been shown to react efficiently with acid chlorides, enones (conjugate addition) and (less efficiently) with primary alkyl iodides and allylic and benzylic bromides (equations 5 and 6). If a suitable ring size can be made, intramolecular reactions with epoxides and ketones are realized. 

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. ... 

The arylbutylselenide 53 readily prepared from the corresponding aryl bromide 54 and lithium butylselenide is an excellent catalyst for the performance of epoxidation reactions in a fluorous biphase system. With 5 mol % of the catalyst 53, various polysubstituted and functionalized olefins 55 are epoxidized in a biphasic system of bromoperfluorooctane and benzene using hydrogen peroxide (60% in water, 1.5-2.0 equiv) leading to epoxides 56 in good to excellent yields Eq. (25). 

Just as epoxides can be prepared from carbonyl compounds, aziridines can be accessed through the addition of amphophilic carbon centers onto imines, and sulfur ylides are frequently used as carbon donors in this regard. Thus, S-allyl tetrahydrothiophenium bromide 139 is smoothly deprotonated with strong base to provide an ylide which adds to a variety of N-protected imines. For the A-tosyl aldimine 140 derived from isovaleraldehyde, the corresponding vinyl aziridine 141 is formed in fair yield as a mixture of stereoisomers <04TL1589>. 

What is the product of the reaction of methylmagnesium bromide with either of the enantiomerically pure epoxides that can be prepared from ( )-3-methyl-2-pentene by the preceding method Assign R or S configurations to the asymmetric carbons of each product. 

Organocopper reagents can be made directly from the bromides and active Cu, which is prepared by reduction of CuCN nLiX with lithium naphthalenide. Copper prepared from Cul PR, (R=Bu, Ph) is most suitable for intramolecular reaction of bromoaryl epoxides to give dihydrobenzofurans. 

Dideoxy-DL-hexoses were prepared from 137 in the following way the carbon atom chain of the substrate was extended to a seven-carbon atom chain by a low temperature Grignard reaction with methylmagnesium bromide. The product obtained, 145, was separately cis-hydroxylated (to stereoisomeric tetraols 14<) or epoxidized (to epoxides 147). Products 146 and 147 were hydrolyzed and subsequently subjected to Ruff degradation. Pairs of stereoisomeric 2,6-dideoxy-DL-hexoses could be separated by column chromatography. Essentially the same approach served for a synthesis of 2-deoxy-DL-eo f/ ra-pentose. In this case compound 138 (X = OH) was used as a substrate for epoxidation. 

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