Bromination-dehydrobromination

An important application of the allylic bromination-dehydrobromination approach is the formation of the A -diene system e.g. 110) in vitamin D synthesis. Dehydrobromination of the A -7-bromo system in the presence of mercuric chloride gives a high yield of A -diene. ... 

The A -double bond can also be introduced in saturated A-nor-2-ketones by bromination-dehydrobromination. This has been used in an alternate preparation of A-norprogesterone" and in a recent synthesis of A-nor-19-nortestosterone. ... 

Dialkylaminobut-3-yn-2-ones (342) can be prepared from 4-dialkylaminobut-3-en-2-ones by the bromination-dehydrobromination procedure (69HCA2641 87ZOR1635). 

Likewise, the isomeric fused aziridines 22 and 24, obtained from 1,4,5,6,7,8-hexahydronaph-thalene, undergo bromination. dehydrobromination and ring expansion to the 6,7,8,9-tetra-hydro-3//-3-benzazepine 23 and the 2,7-bridged azepine 25, respectively.61... 

In a similar manner, bromination, dehydrobromination and amination of l-tosyl-l//-l-benz-azepin-3(2/7)-one yields the 2-amino-3//-l-benzazepin-3-one 10, which condenses with ben-zene-1,2-diamine to give 6//-l-benzazepino[2,3-6]quinoxaline (11).27... 

This method is a modification of the method originally published by Kursanov and Vol pin.6 Tropylium salts have also been prepared by bromination-dehydrobromination of tropili-dene,6 and by the hydride-exchange reaction between tropilidene and triphenylmethyl carbonium ion.7... 

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. 

A similar route—carbonation, bromination, dehydrobromination—produced methyl 4-vinylsalicylate in 28% yield from 3-e thylpheno1 (5). 

Syntheses of the 1,2- and the 3,4-dihydrodiols of MBA via Methods II and IV have been described (74). The 1,2- and 3,4-diol dibenzoates of 1,2,3,4-tetrahydro-MBA prepared from MBA via the Li/-NH reduction route were readily separable by crystallization. Introduction of the olefinic bond into the 1,2-position of the 3,4-diol dibenzoate by the usual bromination-dehydrobromination procedure was complicated by the greater facility of bromination by NBS on the methyl group than the 1-position. This problem was solved (Figure 14) by allowing bromination to proceed to the dibromo stage, followed by selective reduction of the bromomethyl group with NaBH in diglyme. The monobromo derivative underwent dehydrobromination... 

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. 

The mechanism of formation of PhC=CC02H from /raui-PhCH=CHC02H by stepwise bromination-dehydrobromination has been explored. ... 

The bromination-dehydrobromination route is in many cases preferable [Scheme 2 80JCS(P1)2081], using bromine, N-bromosuceinimide (NBS), or phenyltrimethylammonium tribromide (PTAB). The resulting mono-bromo, geminal, or vicinal dibromo and tribromo derivatives (e.g., 5a,b) are often preferentially dehydrobrominated by Jones method [73JCS(P1)968] using lithium salts in dimethylformamide (DMF). Bases such as triethyla-mine, sodium methoxide, and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were also used. 

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. 

The l,3,3,3a,8a-tetrahydro-8-oxa-2-thia- 205, l,3,3,3a,8a-tetrahydro-2,8-dioxa- 206, and 3,3a,8,8a-tetrahydro-12/-2-thia-8-aza-cyclopenta[ ]indene-2,2-dioxide 207 were prepared by Michael addition or radical cyclization from the corresponding sulfones 202-204 and brominated-dehydrobrominated (in the case of 207, after tosylation) to produce 1,5-diheteropentalene systems 208-210, respectively <1997TL5315>. 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

The synthesis started with levoglucosenone 4, available by the pyrolysis of cellulose, e.g. old newspapers. Bromination-dehydrobromination gave the enantiomerically-pure Diels-Alder dienophile 5, which was combined with isoprene to give predominantly the crystalline adduct 1. Hydrolysis and acetylation led to 6, which was carried on to the geometrically-defined allylic alcohol 7 via reduction with Zn-Cu couple. Overman rearrangement of 7 proceeded with high facial control, to give 8. 

The specific construction of trisubstituted alkenes is a continuing challenge. Shigeru Nishiyama of Keio University has described (Tetrahedron Lett. 2004, 45, 8273) the specific bromination-dehydrobromination of the allylic ester 9, delivering 10 as a 60 1 mixture of geometric isomers. Pd-mediated coupling led to the ester 11. 

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). 

Considerable work has been carried out on the aromatic character of the 2-anion (73).202 The, -dioxide of 277-1-benzothiopyran adds diazomethane to yield 74 which is converted into 75 upon bromination/ dehydrobromination.283 Compound 75 also results from the hydrogen... 

The formation of furans from pyrylium salts under oxidative conditions has been mentioned in Section 2.23.2.2. Ring opening and recyclization of 4-chloromethyl-2,6-dimethyI-pyrylium perchlorate (83) by aqueous alkali and DMF leads to 2-methylfuran-4-ylacetone (84) (77CHE918). When 2,3,4,5-tetraphenylpyrylium perbromide is hydrolyzed to the dienone and then subjected to bromination-dehydrobromination, 2-benzoyl-3,4,5-triphenylfuran (85) is formed. 

Firestone et al. (54) heated cottonseed oil at 205° and 225°C in the presence of air. The dimers and higher polymers that were isolated contained moderate amounts of carbonyl and hydroxyl groups and unsaturation difficult to remove by hydrogenation. However, the dimers after bromination-dehydrobromination and oxidation absorbed in the UV region at 250-260 nm and 270-280 nm, indicating the presence of cyclic structures. In addition, Barrett and Henry (55) presented chromatographic and spectral evidence for the presence of dimers in cottonseed oil that had been used for frying. 

Another common method for the preparation of benzene and naphthalene epoxides is by introduction of double bonds into the dihydro precursors. This is generally achieved by bromination-dehydrobromination. Thus unsubstituted benzene oxide-oxepin (86 96) can be obtained by dehydrohalogenation of the dibromocyclohexane epoxide 99, using a basic amine or sodium methoxide in ether.53... 

The reaction of trimethylsilylacetylenedicobalt hexacarbonyl complex and divinyl sulfone in refluxing toluene afforded a dihydrothiepine 1,1-dioxide 218 in 30% yield (Scheme 29) <1999JA8237>. Subsequent bromination-dehydrobromination gave 4-trimethylsilylthiepine 1,1-dioxide 219 in 70% yield. Metalation using [(MeCN )3Cr(CO)3] provided the complex 220 in 85% yield, which was used for [6n+2n] cycloaddition and subsequent Ramberg-Backlund rearrangement (Sections 13.03.5.2 and 13.03.6.2). 

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],... 

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). 

Scheme 6.18 (A) Synthesis of paraphenylacetylene SPMs 68-71 through bromination/dehydrobromination [74] and (B) molecular structure of SPMs 76-78 [75] and onion complex 77 D 76 Qo [76].

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-... 

Reagents i, Br2-NaOAc, H30+ ii, CaC03-DMA iii, H202-Na0H iv, NH2NH2 v, H2-Pd/C vi, PhCO-Cl-py vii, (bromination-dehydrobromination)2 48 viii, LiAlH4 ix, Jones oxidation x, NH2OH. 

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