Bromination-dehydrobromination sequence

The first step in this preparation, the epoxidation of 1,4,5,8-tetra-hydronaphthalene, exemplifies the well-known selectivity exerted by peracids in their reaction with alkenes possessing double bonds that differ in the degree of alkyl substitution.12 As regards the method of aromatization employed in the conversion of ll-oxatricyclo[4.4.1.01-6]-undeca-3,8-diene to l,6-oxido[10]annulene, the two-step bromination-dehydrobromination sequence is given preference to the one-step DDQ-dehydrogenation, which was advantageously applied in the synthesis of l,6-metliano[10]annulene,2,9 since it affords the product in higher yield and purity. 

Base-catalyzed cyclization of A -benzoyl-a-chloroacetamide is a classical method used to prepare 2-phenyl-4(5//)-oxazolone. Extension of this methodology to the A -aroylcinnamides 35 afforded a series of 5-arylidene analogues 37 albeit in unstated yield (Scheme 6.12). " Thus, acylation of the sodium salt of a benzamide with a cinnamoyl chloride gave the imides 35 that were converted to 36 via a bromination-dehydrobromination sequence. Cyclization to 37 was affected with sodium hydride in 1,2-dimethoxyethane (DME). The authors noted that catalytic reduction of 37 afforded the 5-(arylidene)oxazolidine from which 37 could be regenerated in the presence of air. 

A new synthesis of pyrido[4,3-d]pyrimidin-5(6//)ones (48) involves treatment of methyl 2,4-dimethoxy-6-methylpyrimidine-5-carboxylate with LDA in THF at -70 °C followed by the addition of a diary limine. The cycloadducts are aromatised by treatment with NBS via a benzylic bromination-dehydrobromination sequence [91CPB1189],... 

Other useful p-menthane syntheses of no great novelty are of cis- and trans-piperitol from 2a,3o -epoxycarane (silica-catalysed rearrangement to ds-p-menth-2-en-l,8-diol is also reported), of ( )-dihydrocarvone, isopulegone, and p-menthofuran via /S-keto-sulphoxides, of p-mentha-l,4(8)-diene via a bromination-dehydrobromination sequence, and of trans-carveol by benzoyl peroxide-CuCl oxidation of a-pinene. Further details for the conversion of (-)-(142) into (+)-(142), via its epoxide, are reported (Vol. 5, p. 25 cf. Vol. 3, p. 44). " ... 

Reduction of 202a to the lactol and a subsequent Wittig reaction led to 203 in 52% yield. Protecting-group exchange and tosylation of the resulting primary alcohol provided the cyclization precursor 204 (76%). Base treatment then afforded an 87% yield of cyclopentanes 205 epimeric at the nitrile (an epimerizable position). Hydrolysis and esterification of either isomer led to the trans geminally substituted cyclopentane 206 in 82% yield. Reduction of 206 and protection of the ester produced benzyl ether 207, which was converted to alkyne 208 via a bromination-dehydrobromination sequence in 78% yield. 

Scheme 3. Bromination - dehydrobromination sequence giving l,2-dibromo[2.2]paracyclo-phane-l-ene and 1,2,9,10-tetrabromo[2.2]paracyclophane-l,9-diene [19a]...

Terminal acetylenes can be alkylated to give chain-lengthened internal acetylenes in good yield, either by the rapid addition of trialkylalanes in the presence of nickel(ii) catalysts or by electrochemical addition of organoboranes. Hydroalumination may be used in a convenient conversion of terminal olefins into the corresponding acetylenes. An improved procedure for the synthesis of cyclo-octyne from cyclo-octene by a bromination-dehydrobromination sequence has been reported. ... 

Syntheses of diastereomerically pure racemates of himachalene derivatives started from cycloheptanone G (Fig. 9). The sequence to I involved dimethyla-tion to yield H followed by bromination/dehydrobromination and conjugate methylation using cuprate chemistry. The sequence furnishing L and M follows a Robinson-annelation type Reaction of I with 3-(trimethylsilyl)but-3-en-2-one yielded K. Refluxing K with potassium hydroxide in ethanol removed the silyl group and cyclized the diketone to form a 97 3 mixture of racemic L and M. Occurring as a volatile in A.flava, L served as a versatile intermediate in the syntheses of other Aphthona compounds. 

Bienayme and Yezeguelian [63] described a new synthesis of retinal via a Heck vinylation of a C15 tertiary allylic alcohol with a C5 iodoacetal. Thus, the bromo acetal was prepared by a known procedure [64], by a bromination-dehydrobromination reaction sequence (E and Z isomers 40/60). 

Kawase, Oda, and coworkers have synthesized a unique series of belt-shaped paraphenylacetylene macrocydes 68-71 (Scheme 6.18A) and studied their host-guest supramolecular chemistry. The precursor polyenes 72-75 were synthesized using a modified McMurry reaction, and a subsequent bromination/dehydrobro-mination sequence with t-BuOK gave the desired SPMs 68-71. A 4 1 mixture of 72/74 gave the corresponding mixture of SPMs 68 and 70, which could be separated by GPC, while pure samples of 73 and 75 could be obtained to provide 69 and 71 directly [73,74]. Using the same bromination/dehydrobromination procedure, SPMs 76-78 were synthesized with 1,4- or 2,6-naphthylene units, respectively, at opposing positions (Scheme 6.18B). 

The conversions of various steroidal l,4-dien-3-ones (109) into 5-ene-la,3/3-diols (111) via deconjugation to the l,5-dien-3-one, reduction to the l,5-dien-3/8-ol (110), and hydroboration have been described in a series of papers.125 The corresponding 5,7-diene-la,3j8-diols (118), required for photo-isomerization as a key step in the preparation of la-hydroxylated derivatives of vitamin D, have been obtained either by allylic bromination-dehydrobromination of the 5-ene-la,3/3-diols or by the alternative route outlined in Scheme 2. The key step in this reaction sequence is the protection of the 5,7-diene system as the adduct (116) with 4-phenyl-... 

An improved route to 2a-hydroxycholesterol has been devised as part of the preparation of 2a-hydroxy-vitamin D3 (263 R1 = R4 = R5 = R6 = H, R2 = R3 = OH).123 Hydroxylation of the A bond of cholesta-l,5-dien-3/3-ol by means of 9-borabicyclo[3,3,l]nonane followed by reaction with alkaline hydrogen peroxide produced the 2-equatorial 2a,3a-diol in 70—80% yield. The conventional four-step sequence, acetylation, bromination, dehydrobromination, and hydrolysis, gave 2a -hydroxycholesta-5,7-dien-3/3-ol which was converted into 2a-hydroxy-vitamin D3. The isomeric 2/3-hydroxy-vitamin D3 has also been reported.124 Reaction of the 1/6,2/3-oxide obtained by peroxidation of the adduct (265) with lithium aluminium hydride results in a mixture of 2/3,3/3-dihydroxycholest-5,7-diene and its 1/3,3/3-dihydroxy-epimer in the ratio 8 1. Irradiation of the former 5,7-diene furnished the expected previtamin, which on equilibration gave 2/3-hydroxy-vitamin D3 (263 R1 = R4 = R5 = R6 = H, R2 = a-OH, R3 = OH). 

A sequence of bromination-dehydrobromination of a cyclic bisenaminoester yielded the aromatic compound212 (equation 151). 

We have recently converted the ethenyl group of the cinchona alkaloid into an ethynyl group by a bromination-double-dehydrobromination sequence [17, 18]. Bromina-tion of the natural products 1, 2 in CC14 provided the corresponding 10,11-dibromo-cinchona alkaloids in quantitative yield as a yellowish precipitate. The double dehydrobromination to afford alkynes 26 and 27 was studied under a variety of... 

The synthesis of 2(2-hydroxy-5-methy lphenyl)2H-4 -vinyl-benzo-triazole was accomplished (31) by a sequence of reactions similar to those which gave 2H5V. The starting material for this synthesis was, however, not o-nitroaniline but 4-ethyl-o-nitroaniline. After diazo-tiation, the diazonium compounds were allowed to react with p-cresol the condensation product gave 2(2-hydroxy-5-methylphenyl)2H-4-ethyl-benzotriazole after reductive cyclization. This compound was acetyl-ated, brominated, dehydrobrominated, and hydrolyzed to 2(2-hydroxy-5-methylphenyl)2H-4 —viny1-benzotriazole. 

The usual conversion of benzosuberanone (1) into benzo[2,3]tropone (3) involves two bromination and dehydrobromination sequences with moderate yield. Collinton... 

Dibenzo[2.2]paracyclophane-1,9-diene (2), a unique molecule with two parallel sets of mutually orthogonal aromatic rings, was first synthesized in 1985 by Wong et al. [18]. The reported five-step synthesis gave the strained hydrocarbon in only 0.5% yield. Later a more versatile and economic approach to dibenzoannelated [2.2]paracyclophanedienes 11 including the parent compound 2 was developed by de Meijere et al. [19]. The dibromo[2.2]paracyclo-phane-l-ene (6) and the tetrabromo[2.2]paracyclophane-1,9-diene (7) were obtained from commercially available [2.2]paracyclophane (1) in a bromination-dehydrobromination reaction sequence. With compounds 6 and 7 available in large quantities, the palladium catalyzed coupling with alkenes (Heck reaction)... 

Dehydrogenation of 2-oxazolines. This method involves an allylic bromina-tion-dehydrobromination sequence. Since complications of allylic bromination exist for compounds bearing an alkyl group at C-2, the use of PhCOjBu and CuBr is ad- isable in such cases. 

Acetaldehyde is available as in part (a). Alkynes such as acetylene are available from the corresponding alkene by bromination followed by double dehydrobromination. Using ethylene, prepared in part (b), the sequence becomes... 

The enone 445 was then converted to ( )-oxocrinine (415) by a sequence that commenced with the bromination of 445 using excess 5,5-dibromo-2,2-di-methyl-4,6-dioxo-l,3-dioxane to provide a mixture of bromo ketones 446. Removal of the jV-carbobenzyloxy protecting group according to the protocol previously detailed gave 448 as a mixture (a-Br (3-Br = 3 1) of diastereomers, but only the a-bromo isomer underwent dehydrobromination on heating with lithium bromide and lithium carbonate in dry DMF to furnish 415. Interestingly, treatment of the (3-bromo derivative of 448 under similar conditions afforded the debrominated product 447 (200). 

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