Non-rearranged Products Research Articles

Facile synthesis and characterization of indene-fused 4-methylcoumarins and an unexpected skeletal rearrangement via Pechmann condensation

The Pechmann condensation of phenolic fluorenes with ethyl acetoacetate afforded indene-fused 4-methylcoumarins. In addition to the expected indeno[1,2-g]coumarin, a skeletal rearranged compound was obtained as a concomitant product when 9,9-dimethyl-9H-fluorene-2,7-diol was utilized as the substrate. X-ray crystallography was used to identify the structures of the isomers. Photochemical and photophysical studies indicated that compared with the non-rearranged products, the skeletal rearranged isomers have red shifted absorption maxima and much higher fluorescence quantum yields. A mechanism involving two competitive pathways for the simultaneous production of isomers was proposed.

Unusual manganese(III)-mediated oxidative free-radical additions of Meldrum's acid and dimethyl malonate to benzonorbornadiene and oxabenzonorbornadiene

Benzonorbornadiene and 7-oxabenzonorbornadiene were reacted with Meldrum's acid and dimethyl malonate in the presence of Mn(OAc)3 and Cu(OAc)2 in acetic acid. The reaction of benzonorbornadiene with Meldrum's acid gave a naphthalene derivative whereas the reaction with dimethyl malonate formed rearranged products derived from a carbocation intermediate. However, the reaction of 7-oxabenzonorbornadiene with Meldrum's acid gave two nonrearranged products. On the other hand, the reaction with dimethyl malonate unexpectedly formed a dihydronapthalene derivative with an unusual structure. The mechanism for the formation of the products is discussed.

Low and high temperature bromination of 2,3-dicarbomethoxy and 2,3-dicyano benzobarrelene: unexpected substituent effect on bromination

The bromination of 2,3-dicarbomethoxy benzobarrelene yielded the dibromide regio- and stereospecifically arising from the aryl shift where the bromine exclusively attacks the double bond from the exo face of the double bond. High temperature bromination of this compound yielded aryl-shift products. From the low temperature bromination of 2,3-dicyano benzobarrelene, non-rearranged products were obtained along with the rearranged products. Surprisingly, we observed that the yield of non-rearranged products decreased on increasing the temperature. A possible role of the substituent was discussed using DFT calculations on model compounds.

The first and efficient synthesis of some of the polyhalogenated benzobarrelenes: unusual formation of a benzosemibullvalene derivative

New polyhalogenated benzobarrelenes were synthesized in good yields. The bromination reaction of benzobarrelenes at high temperature gives non-rearranged products. Dehydrobromination of the formed products with t-BuOK yielded the desired polyhalogenated benzobarrelenes. The elimination reaction of cyclopropanoid dibromide with a base unusually resulted in the formation of a benzosemibullvalene derivative.

Formate ester synthesis via reaction of 2-bromoethylamines with dimethylformamide

2-Bromoethylamines are converted to the corresponding formate esters in the presence of DMF. Both primary and secondary bromides are smoothly transformed to the esters in satisfactory yields. The reaction mechanism involves the formation of an aziridinium ion, which upon reaction with DMF forms a Vilsmeier-type intermediate that is further hydrolyzed to the corresponding formates. Participation of the β-amino group appears to control not only the regioselectivity but also the stereoselectivity of the reaction. Application of the reaction conditions to chiral substrates indicated that non-rearranged products are formed with retention of configuration at the reacting center.

Bromination of Isomeric 7,8-dibromobenzobicyclo[2.2.2]octa-2,5-dienes: Neighbouring Group Effect on Bromination

The bromination reactions of isomeric 7,8-dibromobenzobicyclo[2.2.2]octa-2,5-dienes were studied and the possible role of neighbouring groups in rearrangements was investigated. Bromination of endo-cis dibromide 9 gives only the rearranged product 14 while the reaction of the exo-cis-dibromide 11 under the same conditions gives only non-rearranged products 15, 16 and 19. The possible role of substituents in the rearrangements was discussed.

Bromination of Endo- and Exo-benzocyclobutenonorbornene Derivatives: Neighbour Group Effect on Bromination

The electrophilic addition of bromine to 13-anti-bromo-endo-benzocyclobutenonorbornene 7 at −50 ± 5 °C has led in high yield to the formation of the rearranged dibromides 9, 10 and 11. In addition to this, bromination of exo isomer 8 results in formation of rearranged 9 and non rearranged product 10. However, high-temperature bromination of endo 7 and exo isomer 8 at 77 °C gave only non-rearranged products. The possible role of a substituent in rearrangements is discussed in these systems.

Synthesis and structure elucidation of bromination products from dibromohomobenzonorbornadienes: high temperature bromination--part 17.

The electrophilic addition of bromine to dibromohomobenzonorbornadiene derivatives at -45 +/- 5 degrees C led to the formation of the rearranged and non-rearranged tetrabromides in a ratio of 6:4. However, high-temperature bromination of the same system in CCl4 at 77 degrees C produced only non-rearranged products. The formation mechanism of the isomers and the role of the substituent on the rearrangement is discussed. The structure elucidation of the isomeric tetrabromides was achieved from NMR spectral data. The agreement between the calculated dihedral angles and the measured coupling constants is especially excellent. The gamma-gauche effect is discussed.

Bromination of an N-carbethoxy-7-aza-2,3-benzonorbornadiene and synthesis of N-carbethoxy-7-aza-2,3-dibromo-5,6-benzonorbornadiene: high temperature bromination. Part 14

The electrophilic addition of bromine to an N-carbethoxy-7-aza-2,3-benzonorbornadiene at 0°C led in high yield to the formation of rearranged dibromides. However, high-temperature bromination of N-carbethoxy-7-aza-2,3-benzonorbornadiene in carbon tetrachloride at 77°C while irradiating, gave exclusively non-rearranged products. From the elimination of these non-rearranged products, N-carbethoxy-4-bromo-7-aza-2,3-benzonorbornadiene was obtained as the sole product. Similarly, bromination of monobromide N-carbethoxy-4-bromo-7-aza-2,3-benzonorbornadiene at 77°C yielded non-rearranged tribromides. The dehydrobromination of these tribromides provided the N-carbethoxy-5,6-dibromo-7-aza-2,3-benzonorbornadiene in high yield, which is a synthon for trimerization reaction.

Bromination of benzobicyclic system with 1,2-dibromotetracholoroethane: unusual radical rearrangement

The bromination reaction of a benzobicyclic system with 1,2-dibromotetracholoroethane (DBTCE) was studied. For tricyclo[6.2.2.0 2,7]dodeca-2,4,6,9,11-pentaene, rearranged and non-rearranged products were obtained. Bromination of 11-oxatricyclo[6.2.1.0 2,7]undeca-2,4,6,9-tetraene with DBTCE gave non-rearranged products whereas brominations of (1 R( S),8 R( S))-9-bromotricyclo[6.2.2.0 2,7]dodeca-2,4,6,9,11-pentaene and (1 S( R),8 S( R))-9,10,11-tribromotricyclo[6.2.2.0 2,7]dodeca-2,4,6,9,11-pentaene with DBTCE gave only rearranged products. In addition, the reaction of (1 S( R),8 S( R))tricyclo[6.3.1.0 2,7]dodeca-2,4,6,9-tetraene with the same reagent resulted in the formation of allylic bromination products. The radicalic reaction mechanism is discussed. All compounds are characterized properly, in particular by NMR spectra and by chemical transformation.

Endo,endo- andexo,exo-Bicyclo[1.1.0]butane-2,4-dimethanol Dimesylate: Synthesis, Structure and Solvolysis

The title compounds endo,endo-9 and exo,exo-9 were prepared from benzvalene. As determined by single-crystal X-ray diffraction, several geometrical parameters of endo,endo-9 are particularly remarkable, namely the large interflap angle of the bicyclo[1.1.0]butane system (128.2°) and the length of the C-1−C-3 bond (151.2 pm). Solvolyses of endo,endo-9 in 60% acetone/water, ethanol and 2,2,2-trifluoroethanol gave rise mainly to cis-5-substituted cyclopent-2-ene-1-methanol mesylates (cis-10, cis-11). Small quantities of the corresponding trans isomers (trans-10,trans-11) suggest a configurational conversion of the intermediate, which is proposed to be the nonclassical pseudoaxial 2-mesyloxymethyl-substituted cyclopent-3-en-1-yl cation (ax-31) formed from endo,endo-9 by heterolytic dissociation accompanied by a Wagner-Meerwein rearrangement. The solvolyses of exo,exo-9 took an entirely different course and afforded nonrearranged products (26, 27) exclusively. This is interpreted in terms of the stereochemical requirements of the Wagner−Meerwein rearrangement, which in the case of exo,exo-9 would result in a highly strained cation such as 32 or 33. In consequence, the generation of the bicyclobutylcarbinyl cation 34 seems to be the most favourable alternative. This result, together with kinetic data for solvolyses of endo,endo-9 and exo,exo-9, casts doubt on a report on solvolyses of the dimethylbicyclo[1.1.0]but-2-ylcarbinyl tosylates 6.4 Solvolyses of endo,endo-9 in several solvents are about 5 times faster than those of the ditosylate 2 (or the corresponding dimesylate), a less flexible bicyclo[1.1.0]butane derivative. That the solvolysis of exo,exo-9 takes place about 8 times more slowly than endo,endo-9 is interpreted by invoking a weaker σ-participation in the case of the former. In comparison to the stereochemically closely related exo,exo-9, the cyclobutanedimethanol ditosylate 28 solvolyses only 50 times more slowly.

High Temperature Bromination. Part 12: Bromination of 7-Oxabenzonorbornadiene: Synthesis of 2,3-Dibromo-7-oxabenzonorbornadiene

The electrophilic addition of bromine to 7-oxabenzonorbornadiene ( 8) at 0°C led in high yield to the formation of dibromoaldehyde 10. However, high-temperature bromination of 8 in carbon tetrachloride at 77°C gave non-rearranged products 17 and 18. From the elimination of non-rearranged products, 2-bromo-7-oxabenzonorbornadiene ( 12) was obtained. Similarly, bromination of monobromide 12 at 77°C yielded the non-rearranged tribromides 19 and 20 while bromination of 12 at 0°C gave the rearranged product 11. The dehydrobromination of tribromides ( 19, 20) provided the 2,3-dibromo-7-oxabenzonorbornadiene ( 21), which is a synthon for the trimerization, in high yield

Ring-enlargement reaction of alkylidenecarbenes bearing a cyclic ether or acetal group. Formation of medium-sized cyclic enol ethers or dienol ethers via bicycloalkenyloxonium ylides

The reaction of 2-acetonyltetrahydrofuran 1a and 2-acetonyltetrahydropyran 1b with the potassium salt of dimethyl diazomethylphosphonate (DAMP) in the presence of MeOH produced ring enlargement product 1-methyl-3-oxacyclooctene 6a (22%) and 1-methyl-3-oxacyclononene 6b (28%), respectively, in addition to nonrearranged products. When the side-chain was elongated by one carbon unit (1c), ring enlargement did not take place. Analogous reactions of 2-acetonyl-substituted 1,3-dioxolane 9a, 1,3-dioxane 9b and 1,3-dioxepane 9c also produced, respectively, 3,5-dimethyl-1,6-dioxacycloocta-2,4-diene (16a, 58%), a mixture (combined yield 83%) of 3,5-dimethyl-1,6-dioxacyclonona-2,4-diene (16b) and 5-exo-methylene-3-methyl-1,6-dioxacyclonon-2-ene (17b), and a mixture (combined yield 54%) of 3,5-dimethyl-1,6-dioxacyclodeca-2,4-diene (16e) and 5-exo-methylene-3-methyl-1,6-dioxacyclodec-2-ene (17e). Side-chain-elongated dioxolane 9d did not undergo enlargement and, instead, ring-switched product 3,6-dimethyl-6-[2-(tert-butyloxy)ethoxy]-5,6-dihydropyran 22 was formed. The formation of products 6, 16, 17 and 22 can be explained in terms of the intermediacy of bicyclooxonium ylides, which are formed in an intramolecular manner between the alkylidenecarbene and a cyclic ether or cyclic acetal unit. In most reactions of acetonyl-substituted cyclic acetals, the major products were di(enol ether)s 16 and 17 even in the presence of a protic nucleophile such as MeOH. A reversible intramolecular process between alkylidenecarbenes and ylides is also proposed.

Bromination of benzhomobarrelene derivatives: 10. High temperature bromination

The electrophilic addition of bromine to benzhomobarrelene derivatives 18a and 18b in CCl 4 at low temperatures (O °C) followed by repeated chromatography combined with fractional crystallization allowed us to isolate seven ( 19a–25a) and five products ( 19b–23b), respectively. Structural determinations of these compounds revealed that the barrelene skeleton was mainly rearranged. Alcohol 24a and ketone 25a are secondary products and arise from 21a and 22a. However, high temperature (77 °C) bromination of compounds 18a and 18b gave only nonrearranged products 19 and 20 whose barrelene skeletons were preserved. It is our conclusion that the low temperature reaction is ionic, where in the high temperature reaction radical intermediates are involved. The mechanism for the formation of the products is discussed and is supported by computational calculations. The structures of 21, 22 and 23 revealed that bromine approachs the double bond from the endo-face of the π-system. The reaction of 18a with m-chloroperbenzoic acid gave only endo-epoxide 40, which in turn supports also the endo-selectivity of the double bond in 18a and 18b.

Solvolysis of Tricyclo[4.1.0.02,7]hept‐4‐en‐3‐yl and Tricyclo[4.1.0.02,7]hept‐3‐yl Methanesulfonates and p‐Nitrobenzoates – Remarkably Small Enthalpy Difference between the C7H7 Cations Tricyclo[4.1.0.02,7]hept‐4‐en‐3‐yl and 7‐Norbornadienyl

AbstractIn an extension of previous work, tricyclo[4.1.0.02,7]heptan‐3‐ol (5) was synthesised in four steps from benzvalene. Methanesulfonates 12 and 6b, c, prepared from 5 and 4‐halotricyclo[4.1.0.02,7]hept‐4‐en‐3‐ols 4b, c, were too unstable to be isolated, but were unambiguously characterised by their NMR spectra. On treatment of the unsubstituted tricycloheptenol 4a with methanesulfonyl chloride, the expected mesylate 6a could not be observed. Even at −40°C, only its consecutive products 3‐chlorotricyclo[4.1.0.02,7]hept‐4‐en (7a) and 7‐chloronorbornadiene (8a) were discernible. The analogous reaction of 6b occurred only at room temperature, with formation of the dichlorotricycloheptene 7b and the dichloronorbornadiene 8b. Rearrangement products of 6b and 12 were the chloronorbornadiene mesylate 10b and anti‐7‐norbornenyl mesylate (13), respectively. – The solvolysis of 6b, c in aqueous ethanol and of 6b in 2,2,2‐trifluoroethanol (TFE) gave nonrearranged products exclusively, i.e. the alcohols 4b, c, the ethyl ethers 17b, c, and the trifluoroethyl ether 18b. In contrast, from 12 only rearranged products arose, namely anti‐7‐norbornenol (30) and its ethyl ether 31. The solvolysis of the unsubstituted tricycloheptenyl p‐nitrobenzoate 11a in 80% aqueous ethanol proceeded about equally fast in parallel reactions with cycloalkyl‐oxygen and acyl‐oxygen cleavage. In addition to the tricycloheptenol 4a, the tricycloheptenyl ethyl ether 17a, ethyl 7‐norbornadienyl ether (19), 7‐norbornadienyl p‐nitrobenzoate (20), and ethyl p‐nitrobenzoate were formed. No acyl‐oxygen cleavage took place in TFE as solvent, where the tricycloheptenyl trifluoroethyl ether 18a, 20, 7‐norbornadienyl trifluoroethyl ether (21), and the cyclopentadienylvinyl trifluoroethyl ethers 22/23 were produced. A new mechanism is proposed for the route to the major products 22/23 via the intermediate 7‐norbornadienyl cation (9a), which was attacked by TFE at the two‐membered bridge stabilising the positive charge. Thus formed, tricyclo‐[3.2.0.02,7]hept‐3‐en‐endo‐6‐yl trifluoroethyl ether (24) underwent a Diels‐Alder cycloreversion generating the cyclopentadienylvinyl trifluoroethyl ether 25, the immediate precursor of 22/23. – From kinetic data for these processes and thermochemical data for appropriate hydrocarbons, the enthalpy difference between the C7H7 cations, tricyclo‐[4.1.0.02,7]hept‐4‐en‐3‐yl (3a) and 7‐norbornadienyl (9a), was calculated to be only 8 kcal mol−1.

High temperature bromination VIII: Bromination of homobenzonorbornadiene

The electrophilic addition of bromine to homobenzonorbornadiene (3) at 10°C led in quantitative yield to the formation of di-anti-bromo adduct 4. However, high-temperature bromination of 3 in decalin at 150°C followed by repeated chromatography combined with fractional crystallization gave us 13 products. Non-rearranged products 5 and 6 have been isolated in 34% yield. The formation of allylic brominated products 8, 9 and 13 (33%) at high temperature have been discussed in terms of free radical mechanism. 14 and 15 are alcohol compounds which arise from hydrolysis of 8, 9, and 13, respectively. All compounds have been characterized properly, especially by 200 MHz 1H NMR and 50 MHz 13C NMR and by chemical transformations. Furthermore, it has been concluded that high temperature bromination of bicyclic systems gives more non-rearranged products. If the molecule is more strained, the tendency to rearrange decreases as in the case of benzonorbornadiene.

Selectivity in the ring-expansion and ring-switching reactions of bicyclooxonium ions

Treatment of ω-(2-oxacycloalkyl)alkyl bromides 5a–e with Ag2O in the presence of a nucleophile (acetic or trifluoroacetic acid) yielded ring-expanded product 8, ring-switched product 7 or/and non-rearranged product 6. Regioselectivity in the nucleophilic attack on the intermediate bicyclooxonium ions 10 governs the product formation. Bicyclo [n.3.0] oxonium ions (n= 3, 4, 5) 10a–c, which can be formed from tetrahydrofuranylalkyl bromides 5a–c, underwent nucleophilic attack at the five-membered ring to produce a ring-switched product 7. Only bicyclo [3.3.0] ion 10a can undergo the preferential attack at the bridgehead position releasing ring strain to produce a ring-expanded product 8 in addition to the formation of 7. Similarly, in the reaction of tetrahydropyranylpropyl and oxepanylpropyl bromides 5d,e, initially formed bicyclo[m+ 2.3.0]oxonium ions (m= 2,3) underwent strain release by cleavage of a five-membered ring resulting in the exclusive formation of non-rearranged products 6d and 6e, respectively. The reason for the observed selectivity is discussed.

High temperature bromination VI: Bromination of benzobarrelene

The electrophilic addition of bromine to benzobarrelene in chloroform at 10° C followed by repeated chromatography combined with fractional crystallization allowed us to isolate ten products 12–21 Structural determination of these compounds revealed that the barrelene skeleton was rearranged completely. 18–21 are alcohol compounds which arise from hydrolysis of 12, 13, 14, and 15, respectively. High temperature bromination of benzobarrelene in decalin at 150 °C followed by repeated chromatography combined with fractional crystallization gave us 18 products. Nonrearranged products 24, 25, and 26 have been isolated in 50% yield. All compounds have been characterized properly, especially by 200 MHz 1H NMR and 50 MHz 13C NMR spectra. Furthermore, it has been concluded that high temperature bromination of bicyclic systems gives more non-rearranged products. If the molecule is more strained, the tendency to rearrange decreases as in the case of benzonorbornadiene.

Synthesis of 2,3-, 2,5-, and 2,6-disubstituted-benzobarrelenes high temperature bromination II

Bromination of 2-bromo-1,4-dihydro-1,4-ethenonaphthalene ( 7) at -0 0C has been found to give five rearranged tribromides 8, 9, 10, 11, and 12 via Wagner-Meerwein rearrangement with accompanying aryl and alkyl migration. It has been shown that the endo tribromides 9and 11 are secondary products formed by bromine-catalyzed reaction of the corresponding exo tribromides. The bromination of 7 at 78 °C resulted in the formation of the non-rearranged products 21, 22, 23, and 24 with bicyclo-[2.2.2]skeleton. The structure of 8, 10, 11 and 21 have been determined by X-ray structural analysis. The dehydrobromination of the tribromides 21, 22, 23, and 24 with potassium tert-butoxide provided the corresponding benzobarrelenes 2a, 3a, and 4a in high yield. Reaction of dibromobenzobarrelenes with CuCN resulted in the formation of dicyano derivatives 2b, 3b, and 3b. Reaction of 3a with BuLi and subsequent quenching with MeI afforded dimethyl derivative 3c.

Number and structure of solvolysis intermediates. Part 1. A comparison of nucleophilic reactions on in situ generated carbocations with solvolysis reactions for 2,2-dimethyl-1-(p-methoxyphenyl)propyl cation

2,2-Dimethyl-1-(p-methoxyphenyl)propyl cation has been generated by treatment of the corresponding chloride with AgSbF6 in SO2–CH2Cl2(20% CD2Cl2) at –98 °C and its 13C NMR spectrum observed. The reactions of the generated carbocation with methanol or phenol give products with a rearranged carbon atom skeleton and non-rearranged products with complete racemization, as expected for a typical carbocation reaction, whereas the solvolysis of the corresponding p-nitrobenzoate in phenol affords exclusively the non-rearranged products with partial retention of configuration. Such distinctions between generated carbocation reactions and the solvolysis reactions indicate that no dissociated (free) carbocation intermediate intervenes even in this solvolysis system, i.e., it is one of a few systems which have been hitherto confirmed to proceed via multiple intermediate stages.