Functionalized dibenzo[g,p]chrysenes: variable photophysical and electronic properties and liquid-crystal chemistry

The photophysical and electronic properties of dibenzo[ g, p]chrysenes bearing electron-rich and -deficient substituents vary markedly with these substituents. The chemistry of the first liquid-crystalline dibenzo[ g, p]chrysene is also described.     

Palladium-catalyzed double cross-coupling reaction of 1,2-bis(pinacolatoboryl)alkenes and -arenes with 2,2′-dibromobiaryls: annulative approach to functionalized polycyclic aromatic hydrocarbons

This study demonstrates that the double cross-coupling reaction of 1,2-bis(pinacolatoboryl)alkenes and -arenes with 2,2′-dibromobiaryls proceeds smoothly with the aid of a catalytic amount of Pd(PPh₃)₄ in the presence of excess base to give a variety of polycyclic aromatic hydrocarbons, such as phenanthrenes, [5]helicene, dithienobenzenes, triphenylenes, dibenzo[g,p]chrysenes, and triphenyleno[1,2-b:4,3-b′]dithiophenes in good to high yields. It is noteworthy that the annulations using 2,2′-dibromooctafluorobiphenyl as an electrophile furnish the otherwise difficult to synthesize octafluorophenanthrenes and semi-fluorinated dibenzo[g,p]chrysenes in high yields.     

Synthesis of [1,3]dithiole and spiro[1,3]dithiole thiopyran derivatives of the [1,2]dithiolo[1,4]thiazine ring system

We report the synthesis of some new polysulfur-nitrogen heterocycles by cycloaddition reactions to readily available tricyclic condensed 1,2-dithiole-3-thiones. Thus, treatment of bis[1,2]dithiolopyrrole ketothione 1 with diacyl acetylenes gave the bis-aducts 2a-d. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine ketothione 3 with 1 equiv of acyl or diacyl acetylenes gave [1,3]dithiolylidenyl[1,2]dithiolo[1,4]thiazines 4a-f in fair to high yields. Catalysis by scandium triflate was used in the reactions that implied the less reactive dipolarophiles. Treatment of 3 with 2 equiv of DBA gave the bis-aduct 5a, and reaction of 4c with DMAD gave the mixed bis-adduct 5b. Cyclic voltammetry of selected examples showed irreversible processes that were influenced by the electrochemical activity of peripheral groups bonded to the heterocyclic system.     

Synthesis of dibenzo[b,d]pyran-6-ones based on [3 + 3] cyclizations of 1,3-bis(silyl enol ethers) with 3-silyloxy-2-en-1-ones

Functionalized dibenzo[b,d]pyran-6-ones were prepared by formal [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 3-silyloxy-2-en-1-ones or 1,1-diacetylcyclopropane to give functionalized salicylates, Suzuki cross-coupling reactions of the corresponding triflates, and subsequent BBr3-mediated lactonization. A second approach to dibenzo[b,d]pyran-6-ones relies on the [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 1-(2-methoxyphenyl)-1-(trimethylsilyloxy)alk-1-en-3-ones and subsequent BBr3-mediated lactonization.     

A rapid and efficient access to diaryldibenzo[b,f][1,5]diazocines

2-Benzoylbenzoyl azides undergo facile cyclization under acidic conditions to give substituted dibenzo[b,f][1,5]-diazocines in good yields. This approach shortens the synthetic steps toward these compounds as compared with conventional methods. The mechanism of the diazocine synthesis is assumed to proceed by an unprecedented intermolecular [2 + 2] cyclization.     

Sequential oxidative transformation of tetraarylethylenes to 9,10-diarylphenanthrenes and dibenzo[g,p]chrysenes using DDQ as an oxidant

Tetraarylethylenes can be sequentially transformed into 9,10-diarylphenanthrenes and dibenzo[g,p]chrysenes using 1 and 2 equiv of DDQ, respectively, in CH(2)Cl(2) containing methanesulfonic acid, in excellent yields. Efficient access to substituted dibenzochrysenes from tetraarylethylenes establishes the versatility of this procedure over the existing multistep syntheses of dibenzochrysenes. Moreover, the ready regeneration of DDQ from easily recovered reduced DDQ-H(2) continues to advance the use of DDQ/H(+) for the oxidative C-C bond forming reactions.     

An efficient approach to azirino and pyrrolo-fused dibenzazepines. Conformations of substituted dibenzo[c,f]pyrrolo[1,2-a]azepines

An effective approach to azepino-fused heterocycles is described. trans-1-Aryl-7,11b-dihydro-1H-azirino[1,2-a]dibenzo[c,f]azepines were synthesised via a domino sequence: isomerization of gem-dichloroaziridine-intramolecular Friedel-Crafts acylation of the tethered benzene ring catalysed by SnCl(4) and subsequent hydride induced intramolecular cyclization. Cycloaddition of dibenzazepinium ylides, generated by heating these aziridines, to activated C[double bond]C, C[triple bond]C dipolarophiles and fullerene C(60), leads to derivatives of dibenzo[c,f]pyrrolo[1,2-a]azepine. The reaction proceeds with complete stereoselectivity via cycloaddition of only W-ylide, which due to the high barrier does not undergo E,Z-isomerization under the reaction conditions. It was found that 2,3,9,13b-tetrahydro-1H-dibenzo[c,f]pyrrolo[1,2-a]azepine systems can exist in conformations of two types depending on the substituents at the pyrrolidine carbons in β-position with respect to nitrogen. Details of cycloaddition reactions and the conformational behavior of cycloadducts were studied by DFT calculations at the B3LYP/6-31G(d) level.     

The diazo route to diazonamide A. Studies on the indole bis-oxazole fragment

[structure: see text] Various approaches to the indole bis-oxazole fragment of the marine secondary metabolite diazonamide A are described, all of which feature dirhodium(II)-catalyzed reactions of diazocarbonyl compounds in key steps. Thus, 3-bromophenylacetaldehyde is converted into an alpha-diazo-beta-ketoester, dirhodium(II)-catalyzed reaction of which with N-Boc-valinamide resulted in N-H insertion of the intermediate rhodium carbene to give a ketoamide that readily underwent cyclodehydration to give (S)-2-(1-tert-butoxycarbonylamino)-2-methylpropyl]-5-(3-bromobenzyl)oxazole-4-carboxamide, after ammonolysis of the initially formed ester. This aryl bromide was then coupled to a 3-formyl-indole-4-boronate under Pd catalysis to give the expected biaryl. Subsequent conversion of the aldehyde group into a second alpha-diazo-beta-ketoester gave a substrate for an intramolecular carbene N-H insertion, although attempts to effect this cyclization were unsuccessful. A second approach to an indole bis-oxazole involved an intermolecular rhodium carbene N-H insertion, followed by oxazole formation to give (S)-2-[1-tert-(butoxycarbonylamino)-2-methylpropyl]-5-methyloxazole-4-carboxamide. A further N-H insertion of this carboxmide with the rhodium carbene derived from ethyl 2-diazo-3-[1-(2-nitrobenzenesulfonyl)indol-3-yl]-3-oxopropanoate gave a ketoamide, cyclodehydration of which gave the desired indole bis-oxazole. Finally, the boronate formed from 4-bromotryptamine was coupled to another diazocarbonyl-derived oxazole to give the corresponding biaryl, deprotection and cyclization of which produced a macrocyclic indole-oxazole derivative. Subsequent oxidation and cyclodehydration incorporated the second oxazole and gave the macrocyclic indole bis-oxazole.     

Aryl radical cyclizations: one-Pot syntheses of protoberberine and pavine alkaloids

Treatment of 2-(2'-bromo-beta-phenethyl)isocarbostyrils 7 with AIBN-Bu(3)SnH in boiling benzene gave 8-oxoberbines 3 in good yields. A similar treatment of 2-(2'-bromo-beta-phenethyl)isoquinolinium bromides 6 and their nor- and homoanalogues (10,11) induced 6-, 5-, and 7-exo radical closures in a one-pot manner to give protoberberines 2, dibenzo[b,g]indolizidine 14a and, dibenzo[a, h]-1-azabicyclo[5.4.0]undecane 15a, respectively. A one-pot radical cyclization of 1-(2'-bromobenzyl)isoquinoline methiodide 18a gave a pavine alkaloid, (+/-)-algemonine (19a).     

Convenient syntheses of dibenzo[c,p]chrysene and its possible proximate and ultimate carcinogens: in vitro metabolism and DNA adduction studies

Dibenzo[c,p]chrysene (DB[c,p]C) is the only hexacyclic polycyclic aromatic hydrocarbon having two fjord regions, both in different chemical environments. Its environmental presence and relative tumorigenic potency are not known due to the lack of synthetic standards. We report here the synthesis of dibenzo[c,p]chrysene (1), its proximate carcinogens, i.e., trans-1,2-dihydroxy-1,2-dihydro-DB[c,p]C (2) and trans-11,12-dihydroxy-11,12-dihydro-DB[c,p]C (3), and possible ultimate carcinogens, i.e., anti-trans-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-DB[c,p]C (4) and anti-trans-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydro-DB[c,p]C (5). The syntheses of 1 and the appropriately methoxy-substituted DB[c,p]C (12 and 27), key intermediates for the synthesis of its proximate and ultimate metabolites, were tried first using a Suzuki cross-coupling reaction. However, the cyclization of olefins (10 and 11) gave poor yields of the desired products. An alternate method was thus developed employing a photochemical approach. The in vitro metabolism of DB[c,p]C was established with the S9 fraction of liver homogenate from phenobarbital/beta-naphthoflavone-induced Sprague-Dawley rats. The major dihydrodiol formed was identified as the fjord region 11,12-dihydroxy-11,12-dihydro-DB[c,p]C, while the major and minor phenols were identified as 11-hydroxy-DB[c,p]C and 12-hydroxy-DB[c,p]C, respectively. Further, the DNA adduction studies with the calf thymus DNA led to a mixture of dA and dG adducts for both fjord region diol epoxides (4 and 5). Interestingly, the dA to dG ratio for 1,2-dihydroxy-3,4-epoxide was much higher (3.2) compared to that of 11,12-dihydroxy-13,14-epoxide (0.5).     

Synthesis of 4H-cyclopenta[c]furans via cooperative PdCl2-FeCl2 catalyzed cascade cyclization reaction involving a novel acyl rearrangement process

We have discovered a novel PdCl(2)-FeCl(2) catalyzed cascade cyclization reaction, which involves a novel acyl rearrangement process. This reaction affords a diverse set of poly-substituted 4H-cyclopenta[c]furan products. The reaction scope of this cascade process is quite broad and various internal acetylenes can be employed.     

An aza cyclopropylcarbinyl-homoallyl radical rearrangement-radical cyclization cascade. Synthesis of dibenzoimidazoazepine and oxazepine derivatives

The cycloaddition of the dibenzoxazepinium W-ylides, generated by heating of trans-1-aryl-7,11b-dihydro-1H-azirino[1,2-a]dibenzo[c,f]azepines, to the C═N double bond of 3-aryl-2H-azirines proceeds endo-stereoselectively giving regioisomeric cycloadducts in ca. 1:1 ratio, in good overall yields. In contrast to the dibenzoxazepinium ylides, the cycloaddition of the dibenzazepinium W-ylide proceeds regioselectively but without exo-endo-stereoselectivity. The reasons for this selectivity of the cycloaddition theoretically were studied at the DFT B3LYP/6-31G(d) level. Heating adducts, (2aRS,13SR,13aRS)-13,13a-diaryl-13,13a-dihydro-1H,2aH-azireno[1',2':3,4]imidazo[1,2-d]dibenzo[b,f][1,4]oxazepines and (2aRS,13SR,13aRS)-13,13a- diphenyl-2a,7,13,13a-tetrahydro-1H-azireno[1',2':3,4]imidazo[1,2-a]dibenzo[c,f]azepine, with an excess of AIBN in toluene gave new polyheterocyclic systems via a novel aza cyclopropylcarbinyl-homoallyl radical rearrangement-radical cyclization cascade. The energy profile of the cascade was studied at the DFT UB3LYP/6-31G(d) level. The transient imidazolinylmethyl radical was trapped by the use of other radical initiators as the corresponding peroxide or alcohol.     

Imino-bridged heterocycles. III . Synthesis of mono-bridgehead substituted 11H-benzo[5,6]cyclohepta[1,2-c]pyridin-6,11-imines by regiospecific amine to olefin cyclizations

Employing regiospecific amine to endocyclic olefin and hydroxylamine to exocyclic olefin cyclizations, we have developed pathways to two isomeric, bridgehead methyl-substituted benzo[5,6]cyclohepta[1,2-c]pyridin-6,11-imines. Acid catalyzed cyclization of 5 to 6 was accomplished under exceedingly mild conditions (silica gel/chloroform), whereas, thermal cyclization of 20 to generate 21 was performed analogously to the dibenzo[a,d]cyclohepten-5,10-imine system.     

Synthesis of 2,3-disubstituted benzo[b]thiophenes via palladium-catalyzed coupling and electrophilic cyclization of terminal acetylenes

2,3-Disubstituted benzo[b]thiophenes have been prepared in excellent yields via coupling of terminal acetylenes with commercially available o-iodothioanisole in the presence of a palladium catalyst and subsequent electrophilic cyclization of the resulting o-(1-alkynyl)thioanisole derivatives. I(2), Br(2), NBS, p-O(2)NC(6)H(4)SCl, and PhSeCl have been utilized as electrophiles. Aryl-, vinyl-, and alkyl-substituted terminal acetylenes undergo this coupling and cyclization to produce excellent yields of benzo[b]thiophenes. (Trimethylsilyl)acetylene also undergoes this coupling/cyclization process with I(2), NBS, and the sulfur and selenium electrophiles to afford the corresponding 2-(trimethylsilyl)benzo[b]thiophenes. However, cyclization of the silyl-containing thioanisole using Br(2) affords 2,3-dibromobenzo[b]thiophene.     

About the synthesis of [1,2]diazepinoindole derivatives from ethyl 2-(1-methylindole)acetate, 2-indole and 3-indoleacetohydrazones

The Vilsmeier-Haack reaction with ethyl 2-(1-methylindole)acetate and N,N-Dimethylamides/phosphorus oxychloride gave (65–85%) of ethyl 2-(3-acyl-1-methylindole)acetates 2 , which when boiled with hydrazine yielded about 90% of 4,5-dihydro-6-methyl-4-oxo-3H[1,2]diazepino[5,6-b]indoles 3. The attempted cyclization of 2-(1-methylindole)acetohydrazones 6 with acyl (acetyl and benzoyl) chlorides/triethylamine, to [1,2]diazepino[5,6-b]indole derivatives was fruitless and the bis(acyl)hydrazones 9 were obtained. Several transformations of 9 are reported. Similarly, the attempted cyclization of 3-indoleacetohydrazones 14 with acetyl chloride/triethylamine to [1,2]diazepino[4,5-b]indole derivatives was also fruitless and the bis(acyl)hydrazones 16 were again obtained.     

Synthesis of thiadiazole, dithietane, and imine derivatives of the [1,2]dithiolo[1,4]thiazine ring system

We report the synthesis of some new polysulfur-nitrogen heterocyclics by cycloaddition reactions to the thioketo group of readily available tricyclic 1,2-dithiole-3-thiones. Thus treatment of bis[1,2]dithiolo[1,4]thiazine ketothione 1 with diaryl nitrile imines generated from hydrazonoyl chlorides 2a-g gave [1,3,4]thiadiazolylidenyl[1,2]dithiolo[1,4]thiazines 4a-g in high yield. Compounds 4a-f, bearing the same substituents in both aryl groups, were stable but the analogous 4g,h with a p-nitrophenyl group on carbon gave the bis[1,2]dithiolo[1,4]thiazine dione 9, probably by cycloreversion and hydrolysis during chromatography. Treatment of 1, the bis[1,2]dithiolopyrrole ketothione 13, and dithione 12 with ethoxycarbonyl azide 11 gave imines 12 and 15 and bisimine 16, respectively, by an alternative fragmentation of the initial cycloadduct in which the 1,2-dithiole ring is retained. Reaction of 1 with TosMIC gave the imino-1,3-dithietane 17.     

Base catalyzed intramolecular cycloaddition of dialkyl(4-hydroxybutyn-2-yl)[3-(<Emphasis Type="Italic">p</Emphasis>-tolyl)propyn-2-yl]ammonium chlorides and intramolecular recyclization of the products obtained

Dialkyl(4-hydroxybutyn-2-yl)[3-(p-tolyl)propyn-2-yl]ammonium chlorides undergo a diene synthesis type intramolecular cyclization in aqueous base medium to give 2,2-dialkyl-4-hydroxymethyl-6-methyl-benzo[f]isoindolinium chlorides. Under conditions of aqueous base fission intramolecular cyclization of the latter gives 4-dialkylaminomethyl-8-methyl-1,3-dihydronaphtho[1,2-c]furans.     

Synthesis and unusual [2+2]-cycloaddition reactions of ethyl 4-chloro-2-oxobut-3-ynoate with unactivated alkenes

The highly activated acetylenes, ethyl 4-chloro-2-oxobut-3-ynoate and ethyl 4-bromo-2-oxobut-3-ynoate, were prepared from readily available bis(trimethylstannyl)acetylene in two steps with high overall yield. An unusual ability of the former to furnish [2+2]-cycloadducts with 1,1-disubstituted alkenes in the absence of irradiation and catalysts was discovered. The cycloaddition of ethyl 4-chloro-2-oxobut-3-ynoate to the 1,2-disubstituted alkenes was shown to be effectively catalyzed with stannic chloride.     

Highly efficient cyclization of o-iodobenzoates with aldehydes catalyzed by cobalt bidentate phosphine complexes: a novel entry to chiral phthalides

Methyl 2-iodobenzoates 1 a-c undergo cyclization reactions with various aromatic aldehydes 2 a-m (RC6H4CHO: R=H 2 a, 4-CH3 2 b, 4-tBu 2 c, 4-OMe 2 d, 3-OMe 2 e, 4-Cl 2 f, 4-CF3 2 g, 4-CN 2 h, 4-Ph 2 i; benzo[d][1,3]dioxole-5-carbaldehyde (2 j), 1-napthaldehyde (2 k), benzofuran-2-carbaldehyde (2 l), and isonicotinaldehyde (2 m)) in the presence of [CoI2(dppe)] (dppe=1,2-bis(diphenylphosphino)ethane) and Zn powder in dry THF at 75 degrees C for 24 h to give the corresponding phthalide derivatives 3 a-m and 3 q-t in good to excellent yields. Under similar reaction conditions, less reactive aliphatic aldehydes, heptanal (2 n), butyraldehyde (2 o), and 2-phenylacetaldehyde (2 p) also underwent cyclization reactions with 1 a to provide 3 n-p, respectively, in fair to good yields. The catalytic reaction can be further extended to cinnamyl aldehyde (2 q) with 1 a to give the corresponding phthalide derivative 3 u. This synthetic method is compatible with a variety of functional groups on the aryl ring of 2. The high efficiency of the cobalt catalyst containing a dppe (dppe=1,2-bis(diphenylphosphino)ethane) ligand encouraged us to investigate the asymmetric version of the present catalytic reaction by employing bidentate chiral ligands. Thus, aromatic aldehydes 2 a-c, 2 f, and 2 g undergo cyclization with 2-iodobenzoate (1 a) smoothly in the presence of [CoI2{(S,S)-dipamp}] ((S,S)-dipamp=(1S,2S)-(+)-bis[2-methoxyphenyl]phenylphosphino)ethane) and zinc powder in THF at 75 degrees C for 24 h, giving the corresponding (S)-phthalides 4 a-e in 81-89% yields with 70-98% ee. A possible mechanism for the present catalytic reaction is proposed.     

Facile assembly of fused benzo[4,5]furo heterocycles

A concise synthesis of fused benzo[4,5]furo heterocycles 18 has been developed. Chemo/regioselective Suzuki coupling between 1,2-dihaloarene 17 and alpha-hydroxyphenylboronic acid or ester 20 gives biaryl phenol 19, which then undergoes copper(I) thiophene-2-carboxylate (CuTC)-mediated intramolecular cyclization to afford 18 in good overall yield. This method has broad substrate scope and allows facile assembly of a wide variety of benzo[4,5]furo heterocycles.