7 Aromatic Compounds ~~ By I. G. C. COUlTS Department of Chemistry and Physics Nottingham Polytechnic Nottingham NG11 8NS 1 General and Theoretical Studies Benzene and the Phenyl Ring.-As a contribution to the continuing search for methods of quantifying aromaticity in molecules Zhou and Parr' have expanded their recent suggestion that absolute hardness (or HOMO-LUMO gap) is such a measure by the introduction of a new concept of relative hardness (relative to a defined hypothetical acyclic reference structure). For over 200 cyclic conjugated molecules predictions of aromaticity using relative and absolute hardness give results in agreement with other measures of aromaticity and it is concluded that relative hardness is a particularly good index for identifying aromatic non-aromatic and anti-aromatic character.The distortion from planarity of highly substituted 1,3,5-tris(diethylamin0)-2,4,6-trinitrobenzene determined by X-ray crystallography has been discussed* in terms of steric and electronic factors; in the ground state the molecule is in a boat form the result of cooperative non-bonded steric repulsion and strong push-pull conjuga- tion while in solution it exists as boat C3 and twist C2 conformers. Application3 of supersonic molecular jet laser spectroscopy has allowed the 'trapping' and structural determination of the most stable conformers of a number of methoxyben-zenes. In each case the methoxy group lies in the plane of the ring; curiously in the methoxytoluenes the meta isomer shows a large barrier to methyl rotation but the methyl groups in the ortho and para isomers are free rotating.Results of a large MRCDI ab initio calculation show4 for the lowest triplet state of the free benzene molecule that the hexagonal conformation is unstable and lies 800cm-' above an almost cylindrical trough. The influence of a P-aryl substituent on the reactivity of aryl alkyl derivatives has long been attributed to phenyl participation in carbocation formation. Evidence for the formation of the simplest example (1) in the gas phase has recently been (1) ' Z. Zhou and R. G. Parr J. Am. Chem. Soc. 1989 111 7371. J. M. Chance B. Kahr A. B. Buda and J. S. Siege] J. Am. Chem. Soc 1989 111 5940. P. J. Breen E. R. Bernstein H. V. Secor and J. L. Seeman J. Am.Chem. Soc. 1989 111 1958. W. J. Buma J. H. van der Waals and M. C. van Hemert J. Am. Chem. Soc. 1989 111 86. 171 172 I. G. C. Courts rep~rted.~ [1-'3C]-2-Phenyl-l-chloroethanewas subjected to y-radiolysis with inter- mediates being trapped with methanol and the I3Clabel in the resulting l-methoxy-2- phenylethane was found to be equally distributed in the ethane carbons. Another archetypal species which has been produced6 in the gas phase is the dehydrophenyl anion (2) generated by abstraction of an ortho proton from fluorobenzene followed by collision-induced dissociation of the resulting anion with helium possibly via a fluoride-benzyne complex. Anion (2) is a relatively weak base and does not exchange with D20. Valence Isomers and Homoaromaticity.-A synthesis of the last elusive valence isomer of benzene 2,2'-bicyclopropenyl (3) has finally been achieved' (Scheme 1).It is stable in solution at -10 "C,but at room temperature surprisingly polymerizes rather than reverting to benzene (a very exothermic process). On treatment with silver tetrafluoroborate it is transformed into Dewar benzene and it forms a bis adduct with cyclopentadiene. By a similar route 2,l '-bicyclopropenyl can be prepared and it is claimed without experimental details that the 1,l'-isomer has also been obtained. Me3Si SiMe3 Me3Si c1 SiMe3 (31 Reagents i MeLi CH2C12;ii Bu,NF 25 mTorr Scheme 1 The ketone-sensitized ph- -Jysis of benzvalene leads to benzene formation or automerization. It has now been demonstrated' that photocycloaddition also occurs with a number of ketones to give oxetanes (4).The valence isomerization of benzoxathiete to monothio-o-benzoquinone has been investigated.' Treatment of (4) S. Fornarini and V. Muraglia J. Am. Chem. SOC.,1989 111 873. S. Gronert and C. H. DePuy J. Am. Chem. SOC.,1989 111 9253. ' W. E. Billups and M. M. Haley Angew. Chem. Int. Ed. Engl. 1989 28 1711. M. Christ1 and M. Braun Angew. Chem. Inf. Ed. EngL 1989 28 601. A. Naghipur K. Reszka A,-M. Sapse and J. W. Lown 1. Am. Chem. SOC.,1989 111 258. Aromatic Compounds hexamethyl Dewar benzene with t-butyl hypochlorite gives by a radical mechanism the chloro compound (5) the reactions of which have been reported." Ab initio calculations on the radical cation states of prismane indicate that they would be less stable than those derived from hexamethyl Dewar benzene." Although there are various theoretical and experimental results which indicate that homoaromatic stabilization is mainly a property of ionic systems with neutral molecules having a very small stabilization energies it has been suggested on the basis of heats of hydrogenation that triquinacene is homoaromatic.This view is challenged by Dewar and Holder,12 who find no evidence of homoaromatic stabiliz- ation from either AM1 or ab initio calculations on the molecule. They suggest that the discrepancy between theoretical and thermodynamic data arises from the effects of twisting in di- tetra- and hexahydrotriquinacenes. In an elegant study Prinzbach and co-~orkers'~ describe the conversion of cis-benzene trioxide into 3,6,9-tris(acceptor-substituted) cis-tris-6-homobenzenes (6) which are now available in gram quantities.They have been shown by NMR to possess C3 symmetry. A companion paper reports14 the preparation of trans-oxa-tris-6-homobenzenes(7). 2 Preparation of Benzenes from Non-aromatic Precursors Collision-induced dissociative chemisorption allows the specific conversion of methane into benzene. A monolayer of methane adsorbed on a Ni"' catalyst at low temperatures and ultra high vacuum is converted by krypton bombardment into methyl radicals. As the temperature is raised these radicals dissociate to adsorbed C2H2and then benzene." The mixed heteropolyacid H5PM~10V2040, dissolved in 1,2-dichloroethane with tetraglyme catalyses the aromatization of cyclic dienes in the presence of molecular oxygen.The reaction proceeds by successive one-electron transfers to the heteropoly system which is then reoxidized by the oxygen; conversion of limonene into p-cymene 10 C. C. Wamser D. D. Ngo,M. J. Rodriquez S. A. Shama and T. L. Tran J. Am. Chem. Soc. 1989,111 2162. K. Raghavachari and H. D. Roth J. Am. Chem. Soc. 1989 111 7132. 12 M. J. S. Dewar and A. J. Holder J. Am. Chem. SOC.,1989 111 5384. 13 W.-D. Braschwitz T. Otten C. Rucker H. Fritz and H. Prinzbach Angew. Chem. Int. Ed. EngL 1989 28 1348. 14 D.-R. Handreck D. Hunkler and H. Prinzbach Angew. Chem. Int. Ed. EngL 1989 28 1351. Is Q. Y. Yang A. D. Johnson K. J. Maynard and S.T. Ceyer J. Am. Chem. Soc. 1989 111 8748. I. G. C. Coutts is precededI6 by isomerization to endocyclic dienes. Moore and co-workers have developed ring expansion of 4-alkynylcyclobutenones as a route to benzoquinones." Compounds (8),readily available from dimethyl squarate undergo mild thermolysis to the ketenes (9) which are thought to cyclize via biradicals (10) to quinones (1 1) (Scheme 2). An alternative cyclization of (9) gives cyclopentenediones as by- products but ketenes derived from 4-alkenylcyclobutenones cyclize only to six- membered rings,18 while 4-chloro-4-aryl- (or alkenyl) cyclobutenones rearrange to p-chl~rophenols.'~ cis-5,6-Dichlorohexafluorocyclohexa-1,3-diene,available by a five-step synthesis from hexafluorobenzene has been used2' as a synthon for that molecule in Diels- Alder reactions.Cycloaddition of acetylenic esters to 1 -methoxy- cyclohexadienes produces alkylsalicylates and resorcinols.21 O\ X (9) I 0 0 R' R2fJR 0 +'0 X Scheme 2 3 Non-aromatic Compounds from Benzene Precursors The rneta-photocycloaddition of ethenes to benzene although of great synthetic potential is a process of notorious complexity. However by judicious choice of substituents on the benzene and ethene it is possible to control the nature of the products; the position of alkene attack is directed by the arene substituent while the use of trans-1,2-dichloroethene gives 6-exo-7-endoadducts such as (12).22A remarkable rate enhancement in the cycloaddition of N-methylmaleimide to the enol l6 R.Neumann and M. Lissel J. Org. Chem. 1989 54 4607. L. D. Foland J. 0.Karlsson S. T. Perri R. Schwabe S. L. Xu S. Patil and H. W. Moore J. Am. Chem. SOC.,1989 111 975. 18 S. T. Pem H. J. Dyke and H. W. Moore J. Org. Chem. 1989,54 2034. 19 S. L. Xu and H. W. Moore J. Org. Chem. 1989 54 4024. 20 W. P. Dailey R. A. Correa E. Harrison and D. M. Lemal J. Org. Chem. 1989 54 5511. 21 C. C. Kanakam N. S. Mani H. Ramanathan and G. S. R. Subba Rao J. Chem. SOC.,Perkin Trans. 1 1989 1907. 22 A. Gilbert P. Heath and P. W. Rodwell J. Chem. SOC.,Perkin Trans. 1 1989 1867. Aromatic Compounds form of 9-anthrone compared with that to anthracene is attributed23to catalytic oxyanion acceleration. Mild heating of a pyrrolo[ 3,2-elindole causes migration via a ‘disallowed’thermal 1,3-shift from oxygen to carbon giving dienone (13) in which benzene aromaticity has been unexpectedly destroyed.24 I CI (12) 4 Substitution in the Benzene Ring Electrophilic Substitution.-In a review2’ Effenberger discusses the use which his group and others have made of 1,3,5-tris(dialkylamino)benzenesas sources of stable arenium ions (a-complexes).Although the role in electrophilic aromatic substitution of such ions is wdll established the participation of .rr-complex intermediates on the potential energy surface is still a subject of debate. The behaviour of arenium ions generated in the gas phase by protonation of alkylbenzenes indicates that they coexist with related .rr-complexes.In the latter the positive charge must become localized on the alkyl moiety permitting alkyl side-chain isomerization (Scheme 3). The observation that the side chains of s-butyl and pentylbenzenium ions isomerize prior to decomposition support the existence of wcomplexes although other mechanisms (e.g. involving proton-bound carbenium ions) cannot be excluded.26 The reactions of bromide and chloride with aryl cations produced by dediazonization of arenediazonium salts is diffusion ~ontrolled.~’ f JI Since cation radicals often take part in complex reaction schemes rather than simple combinations they have been regarded as being of low intrinsic reactivity towards nucleophiles compared with related carbocations. However anodic oxida-23 M.Koerner and B. Rickborn J. Org. Chem. 1989 54 6. 24 R. E. Bolton C. J. Moody and C. W. Rees J. Chem. SOC.,Perkin Trans. I 1989 2136. 25 P. Effenberger Acc. Chem Res. 1989 22 27. 26 R. W. Holman and M. L. Gross J. Am. Chem. SOC.,1989 111 3560. 27 J. P. Lorand Tetrahedron Lett. 1989 30,7337. 176 I. G. C. Coutts tion of 9-phenylanthracene produced a cation radical which reacted an order of magnitude faster with acetate than did the corresponding cation.28 Kochi has continued his advocacy of electron transfer processes in aromatic substitution with an interesting account29 of the nitration of arenes by the reaction of molecular oxygen with arene-nitrosonium charge transfer complexes. This nitration involves initial autoxidation of the complex to a radical ion pair [ArH’+ NO2] followed by collapse to a a-complex and final proton loss.The novel procedure allows quantita- tive nuclear nitration of durene and pentamethylbenzene encouraged by specific coupling of arene cation radical with paramagnetic nitrogen dioxide. In the presence of added base prior proton abstraction leads to free-radical side-chain nitration. This last process has been further investigated in a study3’ of the decay in the presence of bases of radical cations produced by laser excitation of methylbenzene- tetranitromethane complexes. Although the nitration of naphthalene predominantly follows the arenium intermediate pathway application of 15N CIDNP techniques indicates that there is a small but significant contribution from the alternative single-electron transfer route.31 In carbon tetrachloride nitrogen dioxide nitrates naphthalene by a free radical mechanism; mononitration occurs predominantly in the 1-position and there is also appreciable formation of the unusual 1,3-and 2,3-dinitronaphthalenes.The product ratios obtained resemble those observed for nitronaphthalenes formed by atmos- pheric pollution and suggest that these may also arise by free radical processes.32 The nitro groups in microbial natural products such as chloramphenicol result from the oxidation of amine-containing precursors.However when Streptumycesfumanus was cultured in a medium containing K%l8o3 the N/O ratio in the nitro group of the metabolite dioxapyrrolomycin was the same as that in the enriched nitrate indicating that the nitro group is introduced by a process analogous to electrophilic nitration.33 The selective nitration of electron-rich substrates with tetrabromonitrocyc-lohexadienone as the nitronium carrier has been extended34 to anilines.Mononitra- tion of alkylbenzenes with benzoyl nitrate in the presence of a zeolite leads to a preponderance of the para isomer.35 The effectiveness of zeolites in controlling the selective electrophilic halogenation of alkylbenzenes is diminished by hydrogen halides but with propylene oxide as an acid scavenger toluene was para-brominated with 98% ~electivity.~~ In the presence of cetyltrimethylammonium bromide aniline N-methylaniline and N,N-dimethylaniline are brominated with an unusually high ortho/para ratio which rises with increasing bulk of the amine s~bstituent.~’ Ben-zyltrimethylammonium tribromide has been further exploited in the bromination of 28 B.Reitstoen F. Norrsell and V. D. Parker J. Am. Chem. SOC.,1989 111 8463. 29 E. K. Kim and J. K. Kochi J. Org. Chem. 1989,54 1692. 30 J. M. Masnovi S. Sankararaman and J. K. Kochi J. Am. Chem. SOL 1989 111 2263. 31 J. F. Johnston J. H. Ridd and J. P. B. Sandall J. Chem. SOC.,Chem. Commun. 1989 244. 32 G. L. Squadrito F. R. Fronczek D. F. Church and W. A. Pryor J. Org. Chem. 1989 54 548. 33 G. T. Carter J. A. Nietsche J. J. Goodman M. J. Torrey T. S. Dunne M. M. Siegel and D. B. Borders J. Chem. SOC.,Chem Commun. 1989 1271. 34 M. Lemaire A. Guy P. Boutin and J.P. Guette Synthesis 1989 761. 35 K. Smith and K. Fry Tetrahedron Lerr. 1989 30,5333. 36 F. de la Vega and Y. Sasson 1 Chem. SOC.,Chem. Commun. 1989 653. 37 G. Cerichelli L. Luchetti and G. Mancini Tetrahedron Lett. 1989 30,6209. Aromatic Compounds 177 a wide range of phenols38 and has been used to dibrominate 5-a~etoxytropolone.~~ Phenols passed down a column of a polymer-bound form of the reagent are quantitatively brominated although naphthols are oxidized.40 The selective chlorina- tion of electron-rich aromatic compounds with N-chloroamines has been the subject of mechanistic A dominant reaction pathway involves arenium ion intermediacy but electron-transfer processes may be implicated for some alkoxy- substituted benzenes.A perfluoro salt K[(C3F7)3PF3] has been advocated43 as an advantageous replacement for tetrafluoroborates in the Schiemann preparation of fluoroarenes. Aryl cations or cation radicals formed by chemical or anodic oxidation react with the fluoride of hydrogen fluoride/base complexes to yield 4,4-difluoro- cyclohexa-2,5-dienones ( 14) which can be converted4 into a range of fluorophenols (Scheme 4). Anodic oxidation of iodine in trimethyl orthoformate produces iodonium species which effect direct iodination of electron-rich ben~enes.~’ In an adaptati0x-1~~ of the classic synthesis of alkylbenzenes by Friedel-Crafts acylation followed by reduction the intermediate acylation-Lewis acid complex is reduced directly with trimethylsilane. Alkylation of metal phenolates with N-t-Boc-L- prolinal shows4’ high regio- and diastereoselectivity (Scheme 5).With magnesium as counter-ion syn-alcohols (15) are obtained possibly via a-chelation while titanium phenolates yield the anti products (16). OML, -0 + QCHO-x\ * x\ I *+ x\ Boc Boc Boc (15) (16) Scheme 5 38 S. Kajigaeshi T. Kakinami M. Moriwaki T. Tanaka S. Fujisaki and T. Okamoto BUN. Chem. SOC. Jpn. 1989 62 439. 39 T. Nagao A. Mori and H. Takeshita Bull. Chem SOC.Jpn. 1989 62 451. 40 T. Kakinami H. Suenaga T. Yamaguchi T. Okamoto and S. Kajigaeshi Bull Chem. Soc Jpn. 1989 62 3373. 41 F. Minisci E. Vismara F. Fortana E. Platone and G. Faraci J. Chem. SOC,Perkin Trans. 2 1989 123. 42 J. R. Lindsay Smith L. C. McKeer and J. M. Taylor J.Chem SOC., Perkin Trans. 2 1989 1529. 43 N. V. Pavlenko and L. M. Yagupol’skii J. Gen. Chem. USSR 1989,59,469. 44 J. H. H. Meurs D. W. Sopher and W. Eilenberg Angew. Chem. Znt. Ed Engl 1989 28,927. 45 T. Shono Y. Matsumura S. Katoh K. Ikeda and T. Kamada Tetrahedron Lett. 1989 1649. 46 A. Jaxa-Chamiec V. P. Shah and L. I. Kruse J. Chem SOC.,Perkin Trans. I 1989 1705. 47 F. Bigi G. Casnati G. Sartori G. Araldi and G. Bocelli Tetrahedron Lett. 1989 30 1121. I. G. C. Coutts The 0,O-diprotonated dication formed from 2-nitropropene in trifluoromethane- sulphonic acid reacts with benzene or naphthalene to give aryl methyl ketones.48 Bromination of (17) resulted in the formation of (18). This is formally an alkylation of a benzene the first to be initiated by bromination and a mechanism invoking a bromonium ion has been propo~ed."~ Acids of general formula ArCH2S(CH2),C02H can be formed directly from the reaction of phenols with formaldehyde and w-mercaptoalkanoic acids.50 The elec- trophilic reactivity of imidoylnitrenes ROC( =NX)N can be controlled5' by choice of nitrogen substituent.Nitrenes in which X is methanesulphonyl react with arenes containing electron-donating groups to give N-acylisoureas but do not insert into aliphatic carbon-hydrogen bonds.52 Further evidence has been presented53 for hydroxyl radicals being the major reactive species in the hydroxylation of aromatic compounds by Cur-hydrogen peroxide. Aryl halides react with F03SCF21 in the presence of copper the halide being replaced by a trifluoromethyl group in an electron transfer process.54 Aryl Radicals.Data on the relative reactivity of carbon-hydrogen bonds towards phenyl radicals have been based on a measurement of competitive reaction between the radical and carbon tetrachloride or the hydrogen donor. A new determinati~n,~~ relying on competitive abstraction of hydrogen or tritium atoms shows that at low temperatures in the liquid phase the selectivity of the phenyl radical is similar to that of the methyl radical but is less so at high temperature in the gas phase. Oxidation of arylhydrazines with Cu" salts is an interesting new source of aryl radicals,56 reaction of the radical with alkenes being controlled by the copper counter-ion. With copper halide the products (19) are those also formed by Meerwein arylation while with copper sulphate the reduced compounds (20) are formed (Scheme 6).Ar-+ CH,=CH-R .- ArCH,CH(Hal)R + ArCH,CH,R (19) (20) Scheme 6 48 K. Okabe T. Ohwada T. Ohta and K. Shudo J. Org. Chem. 1989 54 733. 49 X. Shi R. Day and B. Miller J. Chem. Soc. Perkin Trans. 1 1989 1166. 50 D. J. R. Massy and A. McKillop Synthesis 1989 253. 51 M. Kawase T. Kitamura and V. Kikugawa J. Org. Chem. 1989 54 3394. 52 H. A. Dabbagh and W. Lwowski J. Org. Chem. 1989 54 3952. 53 M. K. Eberhardt G. Ramirez and E. Ayala J. Org. Chem 1989 54 5922. 54 Q.-Y. Chen and S.-W. Wu J. Chem. SOC.,Perkin Trans. 1 1989 2385. 55 F.-D. Kopinke G. Zimmermann and K. Anders J. Org. Chem. 1989 54 3671. 56 T.Varea M. E. Gonzalez-Nunez J. Rodrigo-Chiner and G.Asesnsio Tetrahedron Lett. 1989,30,4709. Aromatic Compounds A transformation involving aryl radicals has provided an elegant solution to the problem of introducing a 10P-substituent into the 1 lp-arylandrostane series of antigestagens. Treatment of the halogenated intermediate (21) with tributylstannane to produce a free radical resulted in a high yield of (22) arising with high regio- specificity from a 6-endo-trig cy~lization.~' When the homochiral amide (23) was cyclized with tributylstannane or with Co' (salen) the diastereomeric excess of (24) was the same and was unaffected by temperature indicating that like the stannane reaction the cobalt-mediated reaction proceeds by a free radical mechanism.58 The radical reactions of polyfluoro aromatic compounds have been reviewed.59 Substitution via Aryl-Metal Complexes.The activation of arene and alkane hydrocar- bon bonds by homogeneous rhodium complexes has been reviewed.60 A photo-chemical reaction of benzene with a complex of rhodium containing ethene and carbon monoxide as ligands yields propiophenone.61 Salts of 2,6-diphenylphenol with tin62 or niobium63 undergo a facile intramolecular metallation to form (25). The addition of benzene to an otherwise unreactive tantalum(II1) alkyl complex is ~atalysed~~ by di-t-butylsilane. In the presence of tetra(triphenylphosphine)nickel benzene replaces the iodine of a-chloro-w-iodoperfluoroalkanes.65 57 E. Ottow G. Neef and R. Wichert Angew.Chem. Int. Ed. Engl. 1989 28 773. 58 A. J. Clark and K. Jones Tetrahedron Lett. 1989 30,5485. 59 L. S. Kobrina J. Fluorine Chem. 1989 42 301. 60 W. D. Jones and F. J. Feher Acc. Chem. Res. 1989 22 91. 61 C. K. Ghosh and W. A. G. Graham J. Am. Chem. SOC.,1989 111 375. 62 G. D. Smith P. E. Fanwick and 1. P. Rothwell J. Am. Chem. SOC.,1989 111 750. 63 B. D. Steffey R. W. Chesnut J. L. Kerschner P. J. Pellechia P. E. Fanwick and I. P. Rothwell J. Am. Chem. Soc. 1989 111 378. 64 D. H. Berry and Q. Jiang J. Am. Chem. SOC.,1989 111 8049. 65 Q.-L. Zhou and Y.-Z. Huang J. Fluorine Chem. 1989 43 385. I. G. C. Courts Nucleophilic displacement of hydride from arenechromium tricarbonyl complexes is of continuing synthetic use.N-Lithioamides66 add to these complexes to give ArN(R')COR* which can be hydrolysed to anilines whilst attack by the anions of Schiff bases derived from a-amino esters constitutes a route to a-aryl-a-amino esters.67 The thermodynamic control of regioselectivity of addition of carbanions to the complexes has been discussed.68 A neat synthesis of chiral 2-arylpropionic acids includes reaction of the enolate ion of (26) with benzenemanganese tricar- b0ny1.~~ Variations on the functionalization of arenes by palladium-catalysed cross-coup- ling continue to be reported. The reaction of iodobenzene with norbornene in the presence of palladium acetate gave7' (27) but the addition of potassium formate to the mixture led to high yields of (28); other formate salts were less effective.71 An unambiguous synthesis of the isomeric nitrofluorenones includes the coupling of phenylboronic acid with bromonitrotoluene~.~~ Unsymmetric biaryls are produced from aryl iodides and arylfluoro~ilanes~~ and from the reaction of arylboronic acids 66 L.Keller K.Times-Marshall S. Behar and K. Richards Tetrahedron Lett. 1989 30,3373. 67 M. Chaan J.-P. Lavergne and P. Viallefont Synth. Commun. 1989 19 1211. 68 E. P. Kundig V. Desobry D. P. Simmons and E. Wenger J. Am. Chem. SOC.,1989 111 1804. 69 W. H. Miles P. M.Smiley and H. R. Brinkman J. Chem. Soc. Chem. Commun. 1989 1897. 70 0.Reiser M. Weber and A. de Meijere Angew. Chem. Int. Ed. Engl. 1989 29 1037. 71 R. C. Larock and P. L. Johnson J. Chem. SOC.,Chem. Commun.1989 1368. 72 T. Iihama J.-M.Fu M. Bouguignon and V. Snieckus Synthesis 1989 184. 73 Y. Hatanaka S. Fukushima and T. Hiyama Chem. Lett. 1989 1711. Aromatic Compounds with aryl triflate~;~~ palladium also catalyses the reaction of the latter with cyanide75 and with trialkylaluminiums a means of converting phenolic hydroxyl into alkyl sub~tituents.~~ by cross- Monoterpenes such as p-thujaplicin have been ~btained'~ coupling of bromotropolones with organostannanes. Direct formylation7' of aryl chlorides to aldehydes with carbon monoxide is possible in the presence of an (isopropy1phosphine)propanecomplex of palladium whilst a silylative decarbonyla- tion of aromatic acid chlorides provides a new route to aryl~ilanes.~~ Arylations with organobismith reagents have been reviewed." ortho-Metallation.The use of Grignard reagents in organic synthesis has been eclipsed by the rise of organolithiums. However Hauser bases R2NMgBr and magnesium diamides (R2N),Mg easily prepared and stable effect ortho-magnesi- ation" of ester or diethylamide derivatives of benzoic acids; the resulting organo- magnesiums can be quenched by electrophiles. Snieck~s~~.~' has extended his ortho-lithiations of N,N-diethylbenzamides to the preparation of ortho silyl intermediates which can be further elaborated. Secondary P-aminobenzamide (29) is dilithiated with n-butyllithium electrophiles being directed onto the benzamide side chains4. 0 The relative ortho-directing power of methoxy and N,N'-dimethylimidazolidine substituents has been st~died;'~ in the absence of TMEDA the latter is more effective.The use of the MEM blocking group for phenolic hydroxyl in lithiation is com- promised by competing ortho-metallation.86 Further examples of the ortho-alkylation of phenols uia intermediate 1,3,2-benzodioxaborins have appeared.87 Nucleophilic Substitution.-AM1 calculations show that polynitroarenes react with hydroxide ion to form charge transfer complexes with considerable radical character on the arene; the complexes collapse to Meisenheimer intermediates the relative energies of which can be successfully predicted in spite of the neglect of correlation 74 A. Huty I. Beetz and 1. Schumann Tetrahedron 1989 45 6679. 75 K. Takagi and Y. Sakakibara Chem.Lett. 1989 1957. 76 K. Hirota Y. Isobe and Y. Maki J. Chem. SOC.,Perkin Trans. I 1989 2513. 77 M. G. Banwell M. P. Collis G. T. Crisp J. N. Lambert M. E. Reum and J. A. Scoble J. Chem. SOC. Chem. Commun. 1989 616. 78 Y. Ben-David M. Portnoy and D. Milstein J. Chem. Soc. Chem. Commun. 1989 1816. 79 J. D. Rich J. Am. Chem. Soc. 1989 111 5886. J.-P. Finet Chem. Rev. 1989 89 1487. 81 P. E. Eaton C.-H. Lee and Y. Xiong J. Am. Chem. SOC.,1989 111 8016. 82 R. J. Mills N. J. Taylor and V. Snieckus 1. Org. Chem. 1989 54 4372. 83 R. J. Mills and V. Snieckus J. Org. Chem. 1989 54 4386. 84 S. Bengtsson and T. Hogberg J. Org. Chem. 1989 54 4549. 8.5 F. M. Bevan M. E. Euerby and S. J. Qureshi J. Chem. Res. (S) 1989 116. 86 J. Mayrargue M.Essamkaoui and H. Moskowitz Tetrahedron Lett. 1989 30,6867. 87 C. K. Lau H. W. R. Williams S. Tardiff C. Dufresne J. Scheigetz and P. C. Belanger Can. J. Chem. 1989 67 1384. 182 I. G. C.Coutts and thermal energies in such calculations.88 However no spectroscopic evidence was obtained of intermediates arising from SET processes during a study of the reaction of polynitrohalogenobenzeneswith hydroxide.89 Discrepancies in reported equilibrium constants for the reaction of methoxide with 4-cyano-2,6-dinitroanisole may be explained” in part by formation of imido ester (30) Vicarious nucleophilic substitution of nitroarenes can be effected” using trihalogenomethyl carbanions produced by reaction of haloforms with t-butoxide at -70°C. The nitro group of meta-substituted nitrobenzenes is replaced9* by fluoride on reaction with KF-Ph4PBr.Solvolysis of N-tosyl- 0-phenylhydroxylamine in HF-THF leads to the regiospecific formation of 4-fluorophenol- a rare example of introduction of fluorine into an inactivated arene by flu0ride.9~ OMe C-OMe II N-N,N-Dimethyl-2,4-bis(trifluoroacetyl)-l -naphthylamine undergoes ready nucleophilic replacement of the dimethylamino group to yield the corresponding naphthol naphthyl ether or thi~ether.~~ The complexities of the S,,l reaction of sulphanions with dihalogeno benzenes have been further explored.95 A simple ~reparation~~ of 4-[alkyl(aryl)sulphonyl]benzaldehydes involves the reaction of 4-halogenobenzaldehydes with sodium sulphonates.Copper( I) salts supported on alumina or charcoal can effect halide displacement on unactivated aryl halides; notable are the conversion of bromoarenes into iodoarenesy7 and the preparation of phenyl thiocyanates without contamination by isothi~cyanates.~~ The use of perfluoroarenes as protecting groups has been reviewed.99 Hexamethyldisilane acts as a a-donor towards photo-excited benzonitriles yielding radical anions which undergo trimethylsilylation ortho or para to the nitrile.’” Oxidized Benzenes.-For the oxidative coupling of phenols iron( 111) chloride is more effective in the solid state than in solution.’” The geometric isomers of 88 R. Bacaloglu C. A. Bunton and F. Ortega J. Am. Chem. Soc. 1989 111 1041. 89 M. R. Crampton A. B. Davis C.Greenhalgh and J. A. Stevens 1. Chem. Soc. Perkin Trans. 2,1989,675. 90 P. C. M. F. Castilho M. R. Crampton and J. Yarwood J. Chem. Res. (S) 1989 370. 91 M. Makosza and Z. Owczarczyk J. Org. Chem. 1989 54 5094. 92 N. Yazawa H. Suzuki Y. Yoshida 0. Furusawa and Y. Kimura Chem. Lett. 1989 2213. 93 W. R. Dolbier L. Celewicz and K. Ohnishi Tetrahedron Lett. 1989 30 4929. 94 M. Hojo R. Masuda E. Okada and H. Miya Synthesis 1989 870. 95 C. Amatore R. Beugelmans M. Bois-Choussy C. Combellas and A. Thiebault J. Org. Chem. 1989 54 5688. 96 A. Ulman and E. Urankar J. Org. Chem. 1989 54 4691. 97 J. H. Clark C. W. Jones C. V. A. Duke and J. M. Miller J. Chem. Res. (S) 1989 238. 98 J. H. Clark C. W. Jones C. V. A. Duke and J. M. Miller J. Chem. Soc.Chem. Commun. 1989 81. 99 M. Jarman J. Fluorine Chem. 1989 42 3. 100 S. Kyushin Y. Ehara Y. Nakadaira and M. Ohashi J. Chem. Soc. Chem. Commun. 1989 279. 101 F. Toda K. Tanaka and S. Iwata J. Org. Chem. 1989 54 3007. Aromatic Compounds 3,6-dimethoxy-3,6-dimethylcyclohexa- 1,4-diene formed by anodic oxidation of p-xylene in methanol have been separated,lo2 and anodic oxidation of 4-methoxy- anilides yields N-acylated quin~neimines.'~~ Complexing the carbonyl oxygen of quinone monoketals with the aluminium compound MAD encourages 1,4-addition of organometallics to the enone ~ystem,"~ and is a key step in an elegant ~ynthesis'~' of defucogilvocarcin M. The highly functionalized naphthalene (3 1 ) a potential synthon for non-linear polycyclic aromatics has been prepared'06 by Diels- Alder addition of bisketal (32) to diethyl acetylenedicarboxylate whilst regioselective cyclization of substituted butadienes onto 4-sulphonyliminoanthracene-l,9,10-triones provides a precursor of anthracyclinone~.'~~ An uncatalysed thermal [1,3]alkyl shift in the spiro vinyl ether (33) gives'08 the dienone (34) and dienone-phenol rearrangement of (35) proceeds by nitrogen migration rather than the more usual carbon shifts."' 4-Nitroacetophenone under- goes an extraordinary disproportionation to 4-aminobenzophenone and 4-nitroben- zoic acid.'".0 0 H (33) (34) (35) 5 Condensed Polycyclic Aromatic Compounds Structure and Reactivity.-Advances in theoretical and computational techniques have allowed ab initio spin-coupled calculations to be performed on naphthalene."' These show that the correlated v-type electrons in the molecule can be described 102 I.Barba F. Alonso and F. Florencio J. Org. Chem. 1989 54 4365. 103 J. S. Swenton B. R. Bonke C.-P. Chen and C.-T. Chou J. Org. Chem. 1989 54 51. 104 A. J. Stern J. J. Rhode and J. S. Swenton J. Org. Chem. 1989 54 4413. 105 D. J. Hart and G. H. Merriman Tetrahedron Lett. 1989 30,5093. 106 K. A. Parker and S. M. Ruder J. Am. Chem. Soc. 1989 111 5948. 107 F. Farina M. C. Paredes L. hebla and V. Stefani J. Chem. SOC.,Perkin Trans. 1 1989 1597. 108 S. Wang G. W. Morrow and J. S. Swenton J. Org. Chem. 1989 54 5364. 109 Y. Kikugawa T. Kitamura and M. Kawase J. Chem Soc. Chem.Commun. 1989 525. I10 P. Wan and X. Xu J. Org. Chem. 1989 54 4473. 111 M. Sironi D. L. Cooper J. Gerratt and M. Raimondi J. Chem. SOC.,Chem. Commun. 1989 675. I. G. C.Coutts in terms of ten distinct non-orthogonal orbitals with various modes of pairing up of electron spins. The three Kekulk-type structures dominate the wave function and the difference in energy between the full molecule and that of the double-benzenoid valence bond structure is 76 kJ mol-'. Ab initio calculations have been carried out on the heats of formation of hydrocarbons ranging from benzene to coronene.112 The automerization of [1-13C]- or [3-13C]phenanthrene catalysed by an AlC1,-NaCl mixture has been followed by NMR and occurs at 160-220 "C;this contrasts with temperatures above 1000 "C necessary for most polycyclic aromatics.' l3 An updated version of the Pariser-Parr-Pople approach to molecular orbital calculations termed DEWAR-PI has been used to calculate the relative energies of a-complexes for electrophilic substitution at each carbon of a large number of alternant and non- alternant polycyclics.In most cases the positions with lowest energies correspond with those found experimentally to undergo electrophilic attack;'14 further experi- mental data on the electrophilic substitution of fluoranthrene hydrocarbons have been p~b1ished.l'~ The reactivity in the gas phase of 1- and 2-naphthalenyl and 9-anthracenyl radicals towards toluene has been examined; relative rates of arylation and of proton abstraction from methyl may be in terms of reversibility of an initial addition step.Irradiation of 9,lO-dialkoxyoctamethylanthracenesgave 9,lO-Dewar isomers which are less stable than decamethyl-9,lO-Dewar anthracene."' Synthesis.-Reviews have been published on the synthesis of benzenoid polycyclics by titanium deoxygenation118 and by aryne arylation reactions."' A recent example of the latter is the synthesis of an aristolactam alkaloid.12' Eliminative photocycliz- ation of o-methoxystilbenes to phenanthrenes occurs with regioselectivity in H2S04-Bu'OH mixtures.I2l Niobium-catalysed coupling of alkynes with aryl 1,2-dialdehydes gives good yields of 1-naphthols with high regioselectivity.'22 The adduct from homophthalic anhydride and dienone (36) undergoes dyotropic rearrangement to (37) with aromatization as the driving force for intramolecular sigmatropic hydrogen transfer.'' Higher analogues of phenalenone may be obtained'24 by ring enlargement of o-pleiadienequinones with diazoalkane and related cycloocta[ delnaphthalenes mm \ 0 0 OH 0 0 112 J.M. Schulman R. C. Peck and R. L. Disch J. Am. Chem. SOC.,1989 111 5675. 113 A. T. Balaban M. D. Gheorghiu A. Schiketanz and A. Necula 1. Am. Chem. SOC.,1989 111 734. 114 M. J. S. Dewar and R. D. Dennington J. Am. Chem. SOC.,1989 111 3804. 115 M. Minabe B. P. Cho and R. G. Harvey J. Am. Chem. SOC.,1989 111,3809. I16 R. H. Chen S. A. Kafafi and S. E. Stein J. Am. Chem. SOC.,1989 111 1418. 117 M. A. Meador and H. Hart J. Org. Chem. 1989,54 2336.'18 H.N.C.Wong Acc. Chem. Res. 1989 22 145. E. R. Biehl and S. P. Khanapure Acc. Chem. Res. 1989 22 275. J. C. Estevez R. J. Estevez E. Guitan M. C.Villaverde and L. Castedo Tetrahedron Lett. 1989,30,5785. 121 F. B. Malory M. J. Rudolph and S. M. Oh 1. Org. Chem. 1989 54 4619. 122 J. B. Hartung and S. F. Pedersen J. Am. Chem. SOC.,111 5468. 123 A. P. Marchand P. Annapurna W. H. Watson and A. Nagl J. Chem. SOC.,Chem. Commun. 1989,281. 124 J. Ikuina K. Yoshida H. Tagata S. Kumakura and J. Tsunetsugu J. Chem. SOC.,Perkin Trans. 1 1989 1305. Aromatic Compounds 185 are formed by oxidative cleavage of cyclopent[ a]acenaphthylene~.'~~ In enedione (38) available'26 from 1,8-dimethylbiphenylene,the eight-membered ring is formally a cyclooctatetraene dication with two oxyanion substituents.Electron transfer would introduce destabilizing anti-aromatic character and might account for the sluggish reaction of (38) with dienes.12' Metallated cyclopropenone ketals are versatile synthons for various cyclopro- penones including the antibiotic penitricin.'28 Heating cyclohepta[ blfuran-2-one derivatives with vinyl ethers or esters has provided a route to more than forty a~ulenes;'~~ a related strategy was employed13' in the preparation of an azuleno- annulenone. Unstable 1 -hydroxyazulene and 3-hydroxyguaiazulene have been obtained by reduction of their acetyl esters. The 1-hydroxy compound exists only as the enol while the guaiazulene changes to a mixture of its keto form and a dimer.131 Addition of tropylium cation to C3 of an allenylsilane generates a vinyl cation which cyclizes to a dihydroazulene from which the related azulene can be obtained by oxidation with excess tr~pylium.'~~ The palladium-catalysed coupling of arylzinc chlorides with the triflate ester of 2-methoxy-5-hydroxytroponeyielded 5-aryltropones useful colchicine analogues.133 In a regiocontrolled synthesis of 12a,l2b-monosecocolchicine,anion (39) acted as a synthetic equivalent for the 7-methoxy-3-tropyl anion.'34 Although 3,6benzotropone is stable only in a glass at X 00 Li+ (39) 125 D. A. Jackson P. H. Lacy and D. C. C. Smith J. Chem. SOC.,Perkin Trans. I 215. 126 C. F. Wilcox K. R. Lassila G. VanDuyne H. Lu and J. Clardy J. Org. Chem. 1989 54 2190.127 C. F. Wilcox K. R.Lassila and C. E. Young J. Org. Chem. 1989 54 5035. I28 M. Isaka S. Matsuzawa S. Yarnago S. Ejhiri Y. Miyachi and E. Nakarnura J. Org. Chem. 1989 54 4727. I29 T. Nozoe P.-W. Yang C.-P. Wu T.4. Huang T.-H. Lee H. Okai H. Wakabayashi and S. Ishikawa Heterocycles 1989 29 1225. 130 S. Kuroda S. Maeda S. Hirooka M. Ogisu K. Yamazaki I. Shimao and M. Yasunarni Tetrahedron Lett. 1989 30,1557. 13' T. Asao S. Ito and N. Morita Tetrahedron Lett. 1989 30,6693. 132 D. A. Becker and R.L. Danheiser J. Am. Chem. SOC.,1989 111 389. 133 R. M. Keenan and L. I. Kruse Synth. Cornmun. 1989 19 793. 134 M. G. Banwell G. L. Gravatt J. S. Buckleton G. R.Clark and C. E. F. Rickard J. Chem. Soc. Chem. Cornmun. 1989 865. I.G. C. Coutts 77 K its carbonyl absorption at 1506 cm-' may indicate'35 some contribution from the l0T-electron structure (40).Treatment of 9-[ 1-(2,4,6-~ycloheptatriienyl)]-9-xanthydrol with acids produced 9-benzylidenexanthene rather than tropylium cation; calculations indicate'36 that the activation energy of the observed ring-contraction pathway is favoured by 130 kJ mol-'. 0- The theoretical prediction that puckered structures of cyclobutadiene dications should be more stable than planar ones is supported by agreement between observed and ab initio calculated chemical shifts.'37 The 'H NMR of (41) a hydrocarbon analogue of the squarate dianion consists of a singlet at 6 1.7 p.p.m. suggesting aromatic character; 13' NMR techniques have been applied to studies on methylated biphenylene dianion~'~~ and the dibenzo[a,c]cyclonatetraenyl anion.'40 Tricar- bonyl(cyc1oheptatriene)iron complexes have been prepared and the synthetic uses of their anions exp10red.l~' Spectroscopic and hydrogenation experiments have previously suggested that homoazulene has aromatic character; it has now been shown'42 to undergo Friedel- Crafts acylation under very mild conditions the reaction proceeding via the u-complex (42).Rearrangements of 8,8-dimethylbenzohomotropyliumions have been rep01ted.l~~In all-cis-1,4,7,10-cyclododecatetraenethe double bonds are all co- E 135 M. Ohkita T. Tsuji and S. Nishida J. Chem. SOC.,Chem. Commun. 1989 924. 136 I. T. Badejo R. Karaman and J. L. Fry J. Org. Chem.1989 54 4591. 137 M. Bremer and P. von R. Schleyer J. Am. Chem. SOC.,1989 111 1147. 13' W.T. Thorstad N. S. Mills D. Q. Buckelew and L. S. Groves J. Org. Chem. 54 773. 139 J. W. Bausch P. S. Gregory G. A. Olah G. K. S. Prackash P. von R. Schleyer and G. A. Segal J. Am. Chem. Soc. 1989 111 3633. 140 B. Eliasson M. H. Nouri-Sorkhabi L. Trogen I. Sethson U. Edlund A. Sygula and M. Rabonivitz J. Org. Chem. 1989 54 171. 141 M. Nitta M. Nishimura and H. Miyano. J. Chem Soc. Perkin Trans I 1989 1019. 142 L. T. Scott C. A. Sumpter M. Oda and I. Erden Tetrahedron Lett. 1989 30,305. 143 R. F. Childs M. Mahendran M. Sivapalan and P. Nguyen J. Chem. SOC.,Chem. Commun. 1989 27. Aromatic Compounds planar indicating that in this molecule there is an absence of homoaromatic des- tabilization.14 7 Cyclophanes The molecular structure and strain energy of [S]metacyclophane has been calculated using the ab initio STO-3G minimal basis set.Results are in rather better agreement with the X-ray structure than those obtained from previous molecular mechanics or MNDO determination^.'^^ The family of unsymmetrical cyclophanes has been extended by the synthesis of [2,2]orthometacyclophane (43),obtained as a 4:1 syn-anti mixture from the pyrolysis of a bis-~ulphone.'~~ Although the geometries of the meta-substituted ring of both forms of (43)are calculated to be practically identical 13C NMR shows strong deshielding for the C16 in the syn isomer only. (43) Sulphone pyrolyses have also yielded fluorinated [2.2]meta~yclophanes'~~ and methylated [2.2.2]metacyclophanes; 14' the latter adopt folded rather than stepped forms to minimize st.eric repulsion among internal methyl groups.A detailed study of the nitration of [2.2]metacyclophanes has been p~b1ished.l~~ A series of highly strained helical dihetero [2.2]cyclophanes (44)have been synthesized in good yields (for this type of molecule) and the effect of increasing the size of internal substituent R on CD and NMR spectra determined."' The influence on NMR spectra of forming tricarbonylchromium complexes of dithiacyclophanes has been di~cussed.'~~ An example has been discovered of a [2.2]metacyclophanedienewhich fails to undergo spontaneous valence isomerization to a dihydropyrene.' 52 An ingenious 'one pot' 144 A.Krause H. Musso W. Boland R. Ahlrichs R. Gleiter R. Boese and M. Bar Angew. Chem. Znt. Ed. Engl, 1989 28 1379. 145 L. W. Jenneskens J. N. Louwen and F. Bikelhaupt J. Chem. SOC.,Perkin Trans. 2 1989 1893. 146 G. Bodwell L. Emst. M. W. Haenel and H. Hopf Angew. Chem. Int. Ed. Engl. 1989 28 455. 147 M. Tashiro H. Fujimoto A. Tsuge S. Mataka and H. Kobayashi J. Org. Chem. 1989 2012. 148 M. Tashiro T. Watanabe A. Tsuge T. Sawada and S. Mataka J. Org. Chem. 1989 54 2632. 149 M. Tashiro S. Mataka Y. Takezaki M. Takeshita T. Arimura A. Tsuge and T. Yamato J. Org. Chem. 1989 54 451. 150 F. Vogtle A. Ostrowicki P. Knops P. Fischer H. Reuter and M. Jansen J. Chem. SOC.,Chem. Commun 1989 1757. 151 R. H.Mitchell T. K. Vinod G. J. Bodwell and G. W. Bushnell J. Org. Chem. 1989 54 5871. 152 Y.-H. Lai and P. Chen J. Org. Chem. 1989,54 4586. I. G. C.Coutts synthesis of layered systems in which the disc-shaped subunits are bridged 14-annulenes involves the reductive alkylation of dianion (45).lS3Unlike conventional phanes the units are linked by bridging groups within the .rr-system and up to five units have been incorporated in a stack. 2-8 Carcinogenic Aromatic Hydrocarbons The carcinogenicity of aromatic amines may be due in part to their conversion into electrophilic N-aryl- 0-acylhydroxylamines. It has now been that biphenyl- hydroxylamine (46)reacts with 2’-deoxyguanosine to give adducts (47) and from model experiment^'^^ the coupling is probably by an SN2 process.0 2’-deoxy-D:ribose (47) An efficient route to dimethylphenanthrenes involves reaction of naphthynes with furan to afford phenanthrene-1-4-endoxideswhich can be deoxygenated with trimethylsilyl iodide.lS6 Further syntheses have been reported of methylene-bridged benzopyrenes ’” polycyclic phenols 1583159 epoxides 16071 and epoxide diols 162,163 Although the last are commonly regarded as being the ultimate active metabolites in mutagenesis Cavalieri and co-workers have suggested that polycyclic radical cations should also be considered and now report’64 that one-electron oxidation of benzo[ alpyrenes yields intermediates which undergo nucleophilic attack at posi- tion 6;the ease of attack correlates with carcinogenicity.153 J. Alexander M. Ehrenfreund J. Fiedler W.Huber H.-J. Rider and K. Mullen Angew. Chem. Znt. Ed. Engl. 1989 28 1531. 154 M. Famulok F. Bosold and G. Boche Angew. Chem. Znt. Ed. Engl. 1989 28 337. M. Novak K. A. Martin and J. L. Heinrich J. Org. Chem. 1989 54 5430. 156 K.-Y. Jung and M. Koreeda J. Org. Chem. 1989 54 5667. 157 R. J. Young and R. G. Harvey Tetrahedron Lett. 1989 30,6603. 158 S. Kumar P. L. Kole and R. J. Sehgal J. Org. Chem. 1989 54 5272. 159 P. L. Kole S. K. Dubey and S. Kumar J. Org. Chem. 1989 54 845. 160 R. E. Lehr P. L. Kole M. Singh and K. D. Tschappal J. Org. Chem. 1989,54 850. 161 K.L. Platt H. Frank and F. Oesch J. Chem. Soc. Perkin Trans. 1 1989 2229. 162 D. R. Bushman S. J. Grossman D. M. Jerina and R.E. Lehr J. Org. Chem. 1989 54 3533. 163 J. Pataki P. Di Raddo and R. G. Harvey J. Org. Chem. 1989 54 840. 164 P. Cremonesi E. L. Cavalieri and E. G. Rogan J. Org. Chem. 1989 54 3561.