6 Aromatic Compounds By A. P. CHORLTON Zeneca Specialties Hexagon House Blackley Manchesrer M9 3DA UK 1 General and Theoretical Studies In .n systems with localized double bonds the switch from one localization pattern to another symmetry-equivalent one is generally considered to proceed via a delocalized transition state of higher symmetry. Heibrunner and Shaik have proposed a mechanism for double bond fluctuation without passing through a high energy delocalized structure. This model is based on second-order perturbation theory within the Hiickel formalism.' The structures of a number of triannulated benzenes have been studied these show no evidence of bond alternation in a 'Mills-Nixon' fashion. Bond alternation is however observed and this is postulated to arise as a consequence of the degree of 71 character of the annulated rings.2 An empirical aromaticity index has been proposed based on the reversibility of protonation of aromatic ether^.^ Liebman has also developed an experimentally convenient theoretical model for the prediction of relative ar~maticity,~ based on the thermochemical equivalence of phenyl and vinyl groups.The presence of o-benzyne has often been inferred by the observation of infra-red signals at 2085cm-' which is within the normal range associated with C=C triple bonds. Theoretical considerations have led to the conclusion that the ketene C=C plus C=O in cyclopentadienylideneketeneis responsible for this IR feat~re.~ Proof of rn-arynes has been obtained for the first time from an IR spectroscopic study of 2,4-didehydro~henoI.~ The photoelectronic spectrum of o-benzyne has been used to detect its ionization potential; this can then in turn be used as a measure of its singlet-triplet gap.7 It has been found that when benzene molecules are subjected to supersonic jet laser spectroscopy they show a sudden drop of photoionization yield at the onset of the third channel region.8 19FNMR has confirmed the existence of a new type of torsional stereoisomerism.9,10-bis(Trifluorovinyl)phenanthrenehas been shown to exist as a pair of torsional ' E. Heibronner and S. Shaik Helc. Chim. Actu 1992 75 539. K. K. Baldridge and J. S. Siege] J. Am. Chem. Soc. 1992 114. 9583. B. Capon and S. Q. Lew Tetrcihrdron. 1992 48 7823. R. S.Hosmane and J. F. Liebman Tetrahedron Lett. 1992 33 2303. ' A.C. Scheiner and H. F. Schaefer J. Am. Chem. Soc. 1992. 114 4758. ' G. Bucher W. Sander E. Kraka. and D. Cremer Angew. Chrrn.. fnt. Ed. Engl. 1992 31 1230 ' X. Zhang and P. Chen J. Am. Chem. Soc. 1992 114 3147. T. Ichimura. H. Shinohara K. Ohashi and N. Nishi. Bull. Chem. Snc,. Jpn.. 1992 65 234. 141 142 A. P. Chorlton diastereoisomers. The barriers to interconversion of these diastereoisomers is thought to be due to steric effects between the phenanthrene and vinyl moieties.' NMR data has demonstrated that the negative charge of the 2,4,3,5,6~pentamethylbenzene anion is confined to a single resonance-stabilized methylene. No evidence was found for a fluxional carbanion in which protons pass rapidly in a circular fashion from one carbon to the next." The 13C NMR substituent-induced chemical shifts of mono substituted benzene derivatives have been examined.' The structural consequences of a molecular assembly that is deficient in hydrogen bond acceptors has been studied by X-ray crystallography.It was shown that aromatic amines can remedy this unfavourable situation by the formation of weak N-H bonds to the aromatic system and through a change in hybridization of nitrogen.'* Polar/n interactions seem to affect the barrier to rotation of 1,%diary1 napthalenes.' The intramolecular hydrogen bonding in N-alkyl-o-nitroanilines has been studied by the application of solvatochromism.'4 The debate on the homoaromaticity of triquinacene has continued.The heat of hydrogenation of triquinacene (1) is anomalously low and this has been attributed to homoaromaticity caused by the overlap of its three TC orbitals. This claim has been refuted by a number of workers who claim this discrepancy is due to differential relief of strain by di- tetra- and hexahydrotriquinacene. These claims could not be verified by theoretical methods. However a recent MM3 study has given calculated heats of hydrogenation in good agreement with experimental values thus concluding that homoaromaticity in triquinacene and in other neutral hydrocarbons is vanishingly small. Scheme 1 The formation of valence isomers of benzenes from the parent aromatic generally involves their excited states and is therefore a photochemically allowed process.Miki W. R. Dolbier Jr. and K. W. Palmer Tetrahedron Lett. 1992 33 1547. lo F. M. Menger and M.G. Banaszczyk Tetrahedron Lett. 1992 33 301. 0.Exner and M. Budesinsky Coll. Czech. Chem. Commun.,1992 57 497. l2 L. R. Hanton C. A. Hunter and D.H. Purvis J. Chem. SOC..Chem. Commun. 1992 1134. l3 F. Cozzi M. Cinquini R. Anunziata T. Dwyer and J.S. Siegel J. Am. Chem. SOC. 1992 114 5729. l4 R. Cattana J.J. Silber and J. Anunziata Can. J. Chem. 1992 70 2677. '' J. W. Storer and K. N. Houk J. Am. Chem. SOC. 1992 114 1165. Aromatic Compounds has reported the first thermal example of this ‘forbidden’ reaction Scheme (l).16-17 In the rearrangement of Dewar benzene the population of singlet excited benzene is not allowed by energetic constraints.However the thermolysis of (2) is anticipated to release 334 kJ mol- in activation and reaction enthalpy. This is sufficient energy to yield the singlet state of (3) which undergoes rearrangement to quinovalene (4) albeit in low yield.’ * Further examples of this type of rearrangement in cyclophanes have been described.19920 A MC-SCF study of the thermal and photochemical cycloaddition of Dewar benzene has been described.2’ * (3) 1 0 But (5) (4) UV and NMR evidence indicate that the singlet state of 1,2,4,5-tetramethyleneben-zene biradical (5)is kinetically stable; this is contrary to previous experimental studies which favoured a triplet state.22 1,2,4-cyclohexatriene (6) an isobenzene has been generated. Its structure was proved by subsequent trapping reactions; Scheme (2).23Its [2 + 2) cycloaddition with styrene has been the subject of a theoretical 2 Preparation of Benzenes from Non-aromatic Precursors The Diels-Alder reaction is still used routinely to prepare aromatic rings; a recent application is the synthesis of musk odour type arene~.~’ There is continued popularity in the use of a-pyrones as 4n components in the Diels-Alder reaction.26 Two recent l6 S.Miki T. Katayama and Z. Yoshida Chem. Lett. 1992 41. S. Miki T. Ema R. Shimizu H. Nakatsuji and 2. Yoshida Tetrahedron Lett. 1992 33 1619. I* S. Miki 0.Kobayashi H. Kagawa Z. Yoshida and H. Nakatsuji Chem. Left. 1992 65. l9 R. Gleiter and B. Treptow Angew. Chem.. fnt. Ed. Engl. 1992 31 862. 2o S. Miki R.Shimizu and H. Nakatsuji Tetrahedron Lett. 1992 33 953. 1. J. Palmer M. Olivucci F. Bernardi and M.A. Robb J. Org. Chem. 1992 57 5081. ” J. H. Reynolds J. A. Berson K. K. Kumashiro J.C. Duchamp K. W. Zilm A. Rubello and P. Vogel J. Am. Chem. SOC. 1992 114 763. 23 M. Christ] M. Braun and G. Muller Angew. Chem.. In[. Ed. Engl. 1992 31 473. 24 R. Janoschek Angew. Chem. Int. Ed. Engl. 1992 31 477. 25 G. Shi S. Cottens S.A. Shiba and M. Schlosser Tetrahedron 1992 48 10 569. ” K. Afarinka G. H. Posner and V. Vinder J. Org. Chem. 1992 57. 4088. 144 A. P. Chorlton -30°C Scheme 2 examples demonstrated how aromatic rings can be annulated to heterocycles to form carba~oles~~ and indoles.28 o-Quinodimethanes continue to be of interest because of their synthetic utility as effective dienes in Diels-Alder reactions for the construction of polycyclic compounds.Quinodimethanes can be generated under mild conditions by the action of Pd'SmI on the propargylic acetate (7). The resulting napthoquinodimethanes (8) can be trapped with alkenes; subsequent oxidation gives 2,3-substituted anthracenes (9).29 OAc Pd(0). Sm12 -78°C OAc (9) (7) The ring opening of benzocyclobutenes is still the preeminent procedure for the generation of quinodimethanes. This method has been used to prepare 3-amino- symmetrical polymethoxy anthra~enes~~ 2-napthalene carboxylic a~id,~',~ and substituted 2-napth0ls.~~ It is very well exemplified by a one-pot synthesis of anthracenes (Scheme 3).3493 The rearrangement of 1,5-diyne-3-enes to arene- 1,4-diyls (Bergman cyclization Scheme 4) has taken on added significance with the discovery of natural toxins which appear to function by undergoing this rearrangement under mild conditions and '' P.I. Van Brueck P. E. van Duran S. M. Toppet and G. J. Hoornaert J. Chem.Soc. Perkin Trans. I 1992 415. P. M. Jackson and C.J. Moody Tetrahedron 1992 48 7447. 29 J. Inanaga Y. Sugimoto and T. Hanamoto Tetrahedron Lett. 1992 33 7035. j0 K. Kobayashi Y. Kanno S. Seko and H. Suginome J. Chem. Soc.. Prrkin Trans. I 1992 31 1 I. 31 K. Kobayashi Y. Kanno S. Seko and H. Suginome J. Chem. Soc. Chern. Commun. 1992 781. 32 J. J. Fitzgerald N. E. Drysdale and R. A. Olofson Synth. Cornmun. 1992 22 1807. 33 A. Rakeeb Deshmuhk H.Zhang L. Tran and E.R. Biehl J. Org. Chem. 1992 57 2485. 34 A. Rakeeb Deshmukh M. Morgan L. Tran and E. R. Biehl Synthesis 1992 1083. 35 E.R. Biehl M. Dutt B. Fravel and H. Zhang J. Chem. Soc. Chem. Cornmun. 1992 1520. Aromatic Compounds produce DNA strand scission. This has prompted the investigation of this reaction in a number of model CN uBrDl LDmHF--70°C R' R' Scheme 3 X X Scheme 4 The relative rates of cycloaromatization have been correlated to the distance between the terminal alkyne~.~' This assumption has been challenged it has been alternatively proposed that the rate of cycloaromatization is related to the strain release in the transition state.41 Semmelhack has highlighted the dependence of the Bergman cyclization on the nature of the trapping agent and its concentration as well as the wide variation of product distribution with reaction ternperat~re.~~ Tandem Bergman cyclizations have been utilized in a new ring annulation method43 and in the preparation of napthalene (10) from (Z,Z)-deca-3,7-diene- 1,5,9-triyne (11).44 MeOH -6 \ K.C.Nicolaou A. Liu Z. Zeng and S. McComb J. Am. Chem. Soc. 1992 114 9279. " P. Magnus R. Lewis and F. Bennett J. Am. Chem. SOC. 1992 114 2560. A.G. Meyers and P. S. Dragovich J. Am. Chem. Soc. 1992 114 5859. 39 Y. Sakai Y. Bando K. Shishido and M. Shibuya Tetrahedron Lett.. 1992 33. 957. 40 K. C. Nicolaou G. Zuccarello C. Riemer V. A. Estevez and W. M. Dai J. Am. Chem. SOC.,1992 114. 7360. 4' P. Magnus P. Carter J.Elliott R. Lewis J. Harling. T. Pitterna W. E. Bauta. and S. Fortt J. Am. Chem. SOC.,1992 114 2544. 42 M. F. Semmelhack T. Neu and F. Foubelo Tetrahedron Lett. 1992 33 3277. " J. W. Grissom and T. L. Calkins Tetrahedron Lett. 1992 33 2315. 44 K. W. Bharucha R. M. Marsh R. E. Minto and R.G. Bergman J. Am. Chem. Soc. 1992. 114 3120. 146 A. P. Chorlton Meyers has shown that allenic enediynes (12) undergo a mild thermal rearrangement to form aromatic products. This reaction is similar to the Bergman cyclization in that it may proceed via the intermediacy of a biradical (13). This biradical shows substantial polar character which is evidenced by its reaction with methanol to form benzylmethyl ether along with 2-phenylethanol formed from radical rea~tion.~’ Palladium and nickel mediated inter and intra [2 + 2 + 21 electrocylizations of alkynes and alkenes have been used to prepare polycycles containing a central aromatic ring.46-48 D-glucose is converted to aromatics by Eschevichia coli.This reaction is catalysed by a transketolase enzyme. Genetic manipulation of this enzyme has resulted in a two-fold increase in the percentage of D-Glucose which is siphoned into aromatic biosynth- e~is.~’ A Michael-induced ring closure has been effectively used for the regioselective preparation of ~yano-anilines~~ and-phenol~.~The employment of phthalides has allowed cyclohex-2-enones to be used as the Michael acceptor to give direct access to structural subunits of Olivomeyin and related antibiotics (Scheme 5).52 Reagents i Bu‘OLi; ii Raney nickel Scheme 5 In a similar process the intramolecular Wittig reaction is utilized to give 2- naphth~ates.’~ A new general route to 1,2-diarylethylenes has been developed through nucleophilic addition of Grignard reagents to cl-cinnamoyl dithioacetals followed by cationic cyclization in the presence of boron trifluoride (Scheme 6).54 ” A.G.Myers P. S. Dragovich and E.Y. Kuo J. Am. Chem. Soc. 1992 114 9369. 46 F. E. Meyer H. Henniges and A. de Meijere Tetrahedron Lett. 1992 33 8039. ‘’ E. Negishi D. S. Harring Z. Owczarczyk M. M. Mohamad and M. Ay Tetrahedron Lett. 1992,33,3253. 48 P. Bhatarah and E.H. Smith J. Chem. Soc. Perkin Trans. 1 1992 2163. 49 K. M. Draths P. L. Pomplians D. L. Conley J. W. Frost A.Berry G. L. Disbrow R. J. Staversky and J.C. Lievense J. Am. Chem. Soc. 1992 114 3956. 50 G.E. H. Elgemrie A.M. Elzanate and A. K. Mansour J. Chem. SOC.,Perkin Trans. I 1992 1073. R. S. Mali and P. G. Jagtap Tetrahedron Lett. 1992 33 1655. ” D. Mal R. Pal and K.V.S.N. Murty J. Chem. Soc.. Chem. Commun. 1992 821. 53 W. Ding J. Pu and C. Zhang Synthesis 1992 635. ’‘ C. Srinivasa Rao 0.M. Singh H. Ila and H. Junjappa Synthesis 1992 1075. Aromatic Compounds eMgBr_ & OH SMe Me \ \ Scheme 6 The Rh' catalysed reaction of acylcyclopropenes represents a new approach towards substituted phenols Scheme (7).55 OH Scheme 7 This synthesis of phenols complements the more traditional benzannulation reactions of carbene complexes (Scheme 8).563s7 __t R' R$H OH R3 Scheme 8 An alternative method for the preparation of phenols is the thermal rearrangement of cyclobutenones.This procedure has been further exploited to give p-chloro- phenols58 and pentasubstituted phenols (Scheme 9).59 Danheiser has utilized this methodology for the key annulation of the c ring in the total synthesis of Dan Shen.60 55 A. Padwa and S. L. Xu J. Am. Chem. SOC. 1992 114 5881. 56 K.H. Dotz T. Schafer F. Kroll and K. Harms Angew. Chem.. Int. Ed. Engl. 1992 31 1237. 5' D. F. Harvey K. P. Lund and D. A. Neil J. Am. Chem. SOC.,1992 114 8424. " S. L. Xu and H. W. Moore J. Org. Chem. 1992 57 326. 59 D. J. Krysan A. Gurski and L.S. Liebeskind J. Am. Chem. SOC. 1992 114 1412. 6o R. L. Danheiser D.S. Casebier and J. L. Loebach Tetrahedron Lett. 1992 33 1149. 148 A. P. Chorlton M,r&C-R -[M]=O + [MI-R [MI-C-R'0' 0' [MI = U(C5H=J2; R =Me EX,Pr' But Scheme 10 Triscyclopentadienyl uranium alkyl complexes react with carbon monoxide to give alkyl benzenes (Scheme 3 Non-aromatic Compounds from Benzene Precursors Oxidation of methoxyphenols with iodobenzene diacetate in various alcohols as solvent affords the mixed quinone monoketals. When p-methoxylphenol is oxidized in the presence of sorbyl alcohol the mixed quinone monoketal is trapped by an intramolecular Diels-Alder reaction (Scheme 1 1).62 4) -Q Me0 0 Me0 0 Scheme 11 Iodobenzene diacetate is also effective in the oxidation of phenolic-dibenzylbutyro lactones to spirodienones in the synthesis of dibenzocyclooctadiene lignan~.~~ Methoxyphenols can also be oxidized to quinone mono ketals by thallium(nI) nitrate.64 Anodic oxidation of 4-(2'-alkenylpheny1)phenolsaffords trans-dihydroben- zofurans derived from a formal 1,3-0xidative cycloaddition of the phenol to the styrene derivative (Scheme 12).65 C.Villiers R. Adam and M. Ephritikhine J. Chem. SOC.,Chem. Cornrnun. 1992 1555. 62 A. E. Fleck J.A. Hobart and G. W. Morrow Synth. Commun. 1992 22 179. 63 A. Pelter R. S. Ward and A.A. Abd-El-Ghani J. Chem. SOC.,Perkin Trans. 1 1992 2249. 64 F.T. Hong K.S. Lee and C.C. Liao Tetrahedron Lett. 1992 33 1992. 65 B.D. Gates P. Dalidowiez A. Tebben S. Wang and J.S. Swenton J. Ory. Chem. 1992 57 2135. Aromatic Compounds Anodic oxidations have also proved effective for the preparation of 1,4-66 and 1,3-~yclohexadienes.~~ Phenols can be oxidized to hydroquinone under mild condi- tions with copper a-diimine complexes as catalysts.@ Microbial oxidation of chloroaromatics gives chiral diene ~is-diols~~ which have been used in improved methods for the synthesis of (-)-cond~ritol~~ and a keto carbocylic nucleoside ~ynthon.~' ortho-Alkylated a-and /I-naphthols are oxidized with t-butyl hydroperoxide in the presence of Ti(OPr') to the corresponding a-ket~ls.~~ 1,2-dimethoxyarenes (14) can be cleaved to muconic diesters (15) by porphyrin catalysed oxidation with magnesium mon~peroxyphthalate.~ Addition of nucleophiles to an aromatic ring results in non-aromatic products.An example is the addition of alkenyl lead triacetates to 2,6-dimethylphenols (Scheme 13).74 OH 0 Scheme 13 If the aromatic contains a chiral auxiliary nucleophilic addition followed by removal of the auxiliary can give enantiomerically pure products. This methodology 66 I. Bardon and ?. Tornero Tetrahedron 1992 48 9967. 67 G. E. Hawkes J. E. Hawkes F.C. M. Comminos V. L. Pardini and H. Viertler Tetrahedron Lett. 1992 33 8133. J. Sykora E. Brandsteterova and A. Jabconova Synth. Commun. 69 T. Hudlicky E. E. Buros and C.H. Buros SYNLETT. 1992 391. 70 H. A. J. Carless J. Chem. SOC.,Chem. Commun. 1992 234. 71 T. Hudlicky M.G. Natchus and T.C. Nugent Synth. Commun. 1992 151. '' K. Krohn K. Bruggmann D. Doring and P.G. Jones Chrm. Ber.1992 125 2439. 73 I. Artaud H. Grennberg and D. Mansuy J. Chem. Soc. Chem. Commun. 1992 1036. 74 T. W. Hambley R. J. Holmes C. J. Parkinson and J. T. Pinhey J.Chem. SOC.,Perkin Trans. 1 1992,1917. 150 A. P. Chorlton has been put into good effect to give chiral tetralin derivatives (Scheme 14).75 Complexation of arynes with organo-manganese compounds allows previously inert aromatic systems to be attacked by nucleophiles. The use of the neutral hexa- fluorophosphate aryl tricarbonyl manganese complex has increased the number of nucleophiles that can be used effe~tively.~~ The addition of chiral nucleophiles to organo-manganese complexes can be stereoselective and this methodology has been used as the key step in a formal synthesis of (+ )-j~vabione.~~ NO CH2OH -[6{ RMgCl ___) NaBh mR \/ \/ \/ Scheme 14 Aromatic systems can also be broken down by reductive processes.The Birch reduction followed by alkylation of N-alkylnaphthalenes sulfonamides (16) gave the 1,4-dihydrosulfonamide (17) which on heating eliminated SO and amine to give substituted naphthalenes (18).78 9-Methoxyphenanthrene can be reductively aminated by photochemical means to give cis- and trans-9-amino- 10-methoxy-9,10-dihydrophenanthrenein a ratio of 75 :25.79Polynuclear aromatic hydrocarbons can be catalytically reduced using group 5 metal aryloxide compounds to give all-cis products.*' 2-Aryl substituted 3-benzyloxypropan-1-enesgenerally undergo meta photocyclo-addition at the 1,3-position of the benzene ring to give dihydro semibullvalenes (19).*' However aryl substituted 4-phenyloxybut-1-enes undergo [2 + 21 photoaddition to give cyclobutanes (20) which undergo ring opening to give the cyclooctatrienes (21); these can undergo subsequent electrocyclization of the diene unit to give the cyclobutenes (22).The substitution in the aryl ring markedly influences which product 75 L.N. Pridgen M. K. Mokhallalati and M. J. Wu J. Org. Chem. 1992 57 1237. 16 F. Balssa K. Aniss and F. Rose-Munch Tetrahedron Lett. 1992 33 1901. 71 W. H. Miles and H. R. Brikman Tetrahedron Lett. 1992 33 589. 78 H. J.E. Loewenthal and L. Gottlieb J. Org. Chem. 1992 57 2631. 79 M. Yasuda K.Shiomori S. Hamasuna K. Shima and T. Yamashita J. Chem. Soc..Perkin Trans. 2,1992 305.80 J. S. Yu B.C. Ankianiec M.T. Nguyen and I.P. Rothwell J. Am. Chem. Soc. 1992 114 1927. 81 D. C. Blakemore and A. Gilbert J. Chem. Soc.. Perkin Trans. I 1992 2265. Aromatic Compounds The photochemical reaction of octafluoronaphthalene and indene has is f~rmed.~~?~~ been studied and this results in all three cycloaddition modes i.e. 1,2- 1,3- and 1,4- cycloadditions take place.84 9-(5-Anilinohexy1)phenanthrene undergoes 1,3-photocycloaddition to afford a novel polycyclic nitrogen heter~cycle.~ Tetranitromethane forms 1,4-photoadducts with benzene showing that the aromaticity of even benzene can be broken down by this type of reaction.86 Monosubstituted benzene derivatives have been shown to act as a dipolarophile in reaction with tetracyanoethylene oxide (Scheme 1 5).87 Scheme 15 The photolysis of 3P-diarnidophenyl azides gives azepines and anilines the product distribution is dependent on the substituents; evidence is also presented for azirine intermediates.88 R2 S.Y. Al-Qaradawi K. B. Cosstick and A. Gilbert J. Chem. Soc.. Perkin Trans. 1 1992 1145. R3 P. J. Wagner M. Sakamoto and A. E. Madkour J. Am. Chem. Soc. 1992 114 7298. R4 N. Zupancic and B. Sket J. Chem. SOC.,Perkin Trans. 1 1992 179. R5 A. Sugimoto R. Hiraoko H. Inoue and T. Adachi J.Chem. Soc.. Perkin Trans. 1 1992 1559. R6 L. Eberson and M.P. Hartshorn J. Chem. SOC..Chem. Commun. 1992 1563. A. de la Hoz C. Pardo J. Elguero and M. L. Jimeno Monatsh. Chem. 1992 123 99. G.G. Younger and R.A. Bell J. Chem.SOC.,Chem. Commun. 1992 1359. A. P.Chorlton 4 Substitution in the Benzene Ring Electrophilic Substitution.-Aryl iodides are usually more difficult to prepare than other aryl halides and synthetic methods leading to them are relatively few. A number of procedures have been developed. Bis(pyridine)iodonium(I) tetrafluoroborate has been used as a mild source of electrophilic iodine.89 In a similar method N-iodosuccinimide and a catalytic amount of hydroxy(tosy1oxy)iodobenzene (Koser's reagent) have been used for the iodination of polyalkylbenzene~.~~ Direct iodination can also be achieved with iodine and alumina-supported copper(1r) chloride or ~ulfate.~' The search for more selective bromination continues with the use of polymer-bound tetraalkylammonium tribromide.This effects para-bromination of phenols in up to 90%.92Selective ring bromination of alkyl-substituted aromatic hydrocarbons has also been achieved using bromine adsorbed on the surface of alumina without any solvent.93 Aromatics can be chlorinated and brominated in the presence of a N-halosaccharin/pyridinium poly(hydrogen fluoride) system. This reaction avoids the use of any catalyst and takes place under mild conditions. This system is thought to generate the highly polarized halogenomonofluoride which obviates the need for polarization of the halogenation species by a Lewis acid.94 The selective introduction of fluorine into aromatics is difficult to achieve directly generally indirect methods are used of which the Balz-Schiemann is preeminent.This however has a number of limitations one of which is the need to isolate and dry the diazonium fluoroborate which can be hazardous and generally the reaction gives poor yields for carboxyl- and hydroxyl-substituted arylamines. A convenient one-pot conversion of arylamines to fluoroaromatics oia nitrosonium tetrafluoroborate has been developed which avoids these limitation^.^' A number of mild methods have been developed that introduce fluorine regioselectively . Caesium fluoroxysulfate has been used to prepare fluoroaromatics regioselectively under mild conditions by the ips0 substitution of arylboronic acids and hydroxyalkyl gro~ps.~~,~~ Fluorine can also be introduced regioselectively by the treatment of N-aryl-N-hydroxyamides with di- ethylaminosulfur trifiuoride this results in the removal of the hydroxy function and introduction of fluorine at the para position.98 The introduction of the trifluoromethyl group has been reviewed.99 The mechanism of aromatic nitration continues to be the subject of active research.Theoretical calculations have been carried out that go some way to explain the solvent effects and regioselectivity of the reaction."' Aromatic nitration has been shown to take place under very mild conditions with potassium nitrate or nitric acid and boron 89 J. Barguena J. M. Gonzalez M. A. Garcia-Martin P.J. Campos and G. Asensio J. Chem. SOC.,Chem. Commun. 1992 1016. 'O P. Bovonsombat G.J. Angara and E. McNelis SYNLETT 1992 131. " M. Kodomari N. Amanokura K.Takeuchi and S. Yoshitomi Bull. Chem. SOC.Jpn. 1992 65 306. " K. Smith D. M. James I. Matthews and M. R. Bye J. Chem. SOC. Perkin Trans. I 1992 1877. '3 B. C. Ranu D.C. Sarker and R. Chakraborty Synth. Commun. 1992 22 1095. 94 I. Mozek and B. Stek Synth. Commun. 1992 22 2513. 95 D. J. Milner Synth. Commun. 1992 22 73. 96 L. J. Diorazio D. A. Widdowson and J. M. Clough Tetrahedron 1992 48 8073. 9' S. Stauber 1. Kosir and M. Zupan J. Chem. Soc.. Chem. Commun. 1992 275. " Y. Kikugawa K. Matsumoto K. Mitsui and T. Sakamoto J. Chem. SOC.,Chem. Commun. 1992 921. 99 M. A. McClinton and D. A. McClinton Tetrahedron 1992 48 6555. loo K. J. Szdbo A. Hornfeldt and S. Gronowitz J. Am. Chem. Soc. 1992 114 6827. Aromatic Compounds 153 trifluoride monohydratelo' and with nitric acid/trifluoromethanesulfonic anhydr-ide.lo2 Friedel-Crafts alkylation of phenyltrimethylsilane gives a mixture of three regio- isomers with the absence of ipso-substitution.It has been suggested therefore that in Friedel-Crafts alkylation the trimethylsilyl group is a very slightly activating substituent but has essentially no directing effect.lo3 The use of shape selective zeolites in the Friedel-Crafts acylation gives good regioselective control and avoids the use of large quantities of aluminium ch10ride.l'~ Dihydroxy ketones such as (23) are usually obtained by a sequence involving Friedel-Crafts acylation and hydrolysis. A more direct route to these dihydroxy ketones is by a photochemical mediated reaction between an aldehyde and a quinone."' OH OH OH OH 0 (23) It had previously been reported that the persulfate oxidation of aromatic amines (Boyland-Sims oxidation) gave exclusively the o-aminoaryl sulfates (24).It has now been established that the para isomer (25) is also formed and that the arylhyd- roxylamine 0-sulfonate (26) is the probable intermediate in this reacti~n.'~~?~~~ 0+ s,o;-(yoso< + 0 A detailed study has been carried out on the reaction of sulfur trioxide with benzene derivatives containing an oxy-substituent. It was found that the reaction is solvent dependent the use of a polar complexing solvent leading predominantly to the para-sulfonic acid whereas dichloromethane or trichlorofluoromethane lead to the ortho-sulfonic acid.' 08,'09 In a further example of regiospecific sulfonation the ortho- and meta-hydroxybenzenesulfonic acids were obtained from the silylation of the lo' G.A.Olah Q. Wang X. Li and I. Bucsi Synthesis 1992 1085. Io2 G. A. Olah V. P. Reddy and G. K. Surya Prakash Synthesis 1992 1087. lo' H. Ishibashi H. Sakashita and M. Ikeda J. Chem. SOC.,Perkin Trans. 1 1992 1953. Io4 G. Harvey and G. Mader Coll. Czech. Chem. Cornmun. 1992 57 862. lo' G. A. Kraus and M. Kirihara J. Org. Chem. 1992 57 3256. Io6 E.J. Behrman J. Chem. SOC.,Perkin Trans. 1 1992 305. lo' E.J. Behrman J. Org. Chem. 1992 57 2266. lo* H. R. W. Ansink and H. Cerfontain Recl. Trav. Chim. Pays-Bas 1992 111 183. Io9 H. R. W. Ansink and H. Cerfontain Recl. Trav. Chim. Pays-Bas 1992 111 215. 154 A.P. Chorlton corresponding chlorophenols followed by ipso-sulfonation of the arylsilane intermedi- ates.' lo A one-pot synthesis of diarylsulfones has been developed. In this procedure an alkylbenzene (27) is treated with HS0,F-SbF,; this initially gives the p-sulfonylfluor- ide (28) which can be isolated but can be allowed to react in situ to give diarylsulfone (29)."' If HS0,-SbF is reacted with alkylbenzenes under an atmosphere of carbon monoxide the para-formyl compound (30) is first formed followed by further reaction to give the 2-(sulfony~fluoride)-4-formylalkylbenzene derivative (31).' ' A ready formylation of anilines has been developed using dimethyl sulfoxide/HCl 4-aminobenzaldehydes are formed in high yields. Chloromethyl methyl sulfoxide is thought to be the active species in this reaction.'13 Aromatic oximes have been prepared directly by the reaction of primary nitroalkanes with aromatics in triflic acid.The regioselectivity is in agreement with electrophilic aromatic substitution but fails for strongly deactivated aromatic^."^ The nitrile moiety can be introduced into electron-rich aromatics in moderate to good yields with activated arylcyanates using AICl,/HCl; the formation of the p-isomers is preferred.' Nucleophilic Substitution.-The mechanism of nucleophilic substitution of aromatic halides has been widely investigated. It appears that the first stage in this reaction is not the formation of a Meisenheimer adduct but an electron transfer process leading to radical intermediates.Grossi has reported the first experimental evidence from EPR spectroscopy for the radical species involved in such reactions. l6 The rate constants for the nucleophilic aromatic substitution reaction of 2,4-dinitrochlorobenzeneand picryl chloride have been measured and when used in combination with other literature data have been shown to correlate well with Ritchie's N+ parameter.'17 'lo P. Babin B. Bennetau P. Bourgeois and J. Dunogues Bull. SOC.Chim. Fr. 1992 129 25. M. Tanaka and Y. Souma J. Org. Chem. 1992 57 3738. '12 M. Tanaka J. Iyoda and Y. Souma J. Org. Chem. 1992 57 2677. '13 B. Liedholm J. Org. Chem. 1992 2235. 'I4 J. Coustard J. Jacquesy and B. Violeau Tetrahedron Lett. 1992 33 8085. K. Buttke T. Reiher and H. J. Niclas Synth. Commun.1992 22 2237. '16 L. Grossi Tetrahedron 1992 33 5645. J.R. Candler I.U. Setiarahardjo C. Tufon and C. Chen J. Org. Chem. 1992 57,4169. Aromatic Compounds Vicarious nucleophilic substitution has become more useful as the range of nucleophiles has increased. Amination of nitroarenes is now possible via the use of sulfenamides (Scheme 16).'l8 A certain degree of regioselectivity can also be achieved by variation of the base used. An intramolecular variant of the vicarious nucleophilic process has been developed which allows the synthesis of benzosultans.' l9 Scheme 16 In a similar process cyclic guanidines have been produced without the aid of a vicarious leaving group. The yields of the products are only moderate because a disproportionation reaction of the starting material is necessary for the elimination of the hydride ion.'*' The regioselectivity of intramolecular aromatic substitution to give benzodiazepines has been examined.12' A further advance has been made in nucleophilic aromatic substitution of hydrogen.Aniline in the presence of tetramethylammonium hydroxide attacks nitrobenzene to give N-(4-nitrosophenyl)phenylaminein 89% yield. In this process there is no auxiliary leaving group or external oxidant the formal oxidation takes place by an intermolecular redox process. 22 Nucleophilic aromatic substitution of isomeric chlorotoluenes can be facilitated by complexation with a cyclopentadienyl iron moiety. The resultant complexes undergo reaction with ethyl cyanoacetate followed by photolytic decomplexation to yield ethyl tolyl cyan~acetates.'~~ The position of nucleophilic attack of 4-(dimethy1amino)azobenzeneis controlled by the organometallic reagent used.Methyllithium adds ortho to the azo in the electron rich aminophenyl ring whereas organo-iron reagents add ortho to the azo in the less electron rich ring (Scheme 17).124 R'X = MeLi R' = Me R2 = H R'X = MQFeLi R' = H R2 = Me Scheme 17 M. Makosza and M. Bialecki J. Org. Chem. 1992 57 4784. K. Wojciechowski and M. Makosza Synthesis 1992 571. lZo F. Esser and K. Pook Synthesis 1992 596. K.A. Parker and C.A. Coburn J. Org. Chem. 1992 57 97. lZ2 M. K. Stern F.D. Hileman and J. K. Bashkin J. Am. Chem. SOC.. 1992 114 9237. A. S. Abd-El-Aziz and C. R. de Renus Synrh.Commun. 1992 22 581. T. Kauffmann J. Jordan and J. Sanders Chem. Ber. 1992 153. A. P. Chorlton The copper (I) halide catalysed reaction of aromatic halides with sodium alkoxides has been studied with reference to the solvent halogen temperature and rate of reaction. 12' The preparation of diphenyl ethers by the Ullmann reaction is catalysed by alkali-metal carbonates in combination with silica and aluminium silicates. The silyl ether formed from an aromatic halide and the silanol group on the surface of silica is presumed to be the intermediate of etherification.'26 The Ullmann reaction can take place at milder temperatures and gives improved yields with the use of ~1trasound.l~~ Microwave irradiation has been shown to accelerate the rate of ethoxylation of ortho and para-nitrochlorobenzenes by up to 240 fold.' 28 The ring opening reaction of (methy1enedioxy)benzenes (32) with propanethiolate in DMF leads to products (33) or (34) depending on the nature of (Z).Where Z = NO (33) is formed in 98% yield.Where Z is a more electron rich substituent e.g. CONH, nucleophilic attack takes place at the methylenedioxy carbon to give (34).129 Z 04 Z L O SPr OH (33) (34) Two groups of workers have independently reported the conversion of 1,2-dichlorobenzenes to 2-nitrophenols with nitrite in a dipolar aprotic media.' 303 '3' Nucleophilic fluorination of aromatic compounds containing suitable leaving groups is generally achieved by the use of KF or CsF in DMSO or sulfolane at high temperatures.This often leads to decomposition of base-susceptible substrates. Tetrabutylphosphonium fluoride and dihydrogen trifluoride can be used under milder conditions in polar solvents to furnish fluoroaromatics in excellent yield.' 32 A new methodology has been developed for the synthesis of a-aryl ketones (2)-Arylazo t-butyl sulfides react with ketone enolates via an S,,1 process to give a-aryl ketones.'33 Substitution via Organometallic Intermediates.-The geometry of the substitution at bromine in the bromine-lithium exchange reaction between a primary alkyllithium reagent has been evaluated by the endocyclic restriction test. The experiments have established that there is a geometrical dependence in these reactions and this combined with the failure of external bromide to become incorporated into the products appears to rule out both a four-centre concerted mechanism and a single 12' M.A. Keegstra T. H. A. Peters and L. Brandsma Tetrahedron 1992 48 3633. 126 I. Fukawa T. Tanabe and T. Dozono J. Chem. SOC.,Perkin Trans. 2 1992 377. 12' K. Smith and D. Jones J. Chem. SOC..Perkin Trans. 1 1992 407. Y. Yuncheng G. Dabin and J. Yulin Synth. Commun. 1992 22 2117. B. K. Cassels C. Radetski and M. C. Rezende Red. Trau. Chim. Pays-Bas 1992 111 448. I3O J. Zilberman D. Ioffe and I. Gozlan Synthesis 1992 659. 13' Y. Uchibori M. Umeno H. Seto Z. Qian and H. Yoshioka SYNLETT 1992 345. 132 L.R. Caswell M. Guevara L.D. Corley A.V. Martinez T. Hollis K. Largess and D.L. Thornley Synthesis 1992 823. 133 C. Dellerba M.Novi G. Petrillo and C. Tavani Tetrahedron 1992 48 325. Aromatic Compounds electron transfer mechanism. The reaction is suggested to proceed uia an ate complex or an S,2 type transition state.'34 Directed ortho metalation (DoM) has developed into a standard synthetic technique. Snieckus has continued to exploit the use of the ortho lithiated N,N-diethylbenzamide group which when reacted with a variety of electrophiles gives access to phthalides phthalic anhydrides and benzofurans all of which were only available by demanding classical methods.' 35,136 Heathcock has also used this methodology as the key step in the synthesis of Pancrastistatin models. In this example 1-nitrocyclohexene is added to in a 1,4-fashion by an ortho-lithiated benzamide.' 37 A number of other DoM groups have been investigated; these include t-butyl sulfox- ide,13* flu~rine,'~~*'~~ and thi01.l~' The anionic Fries rearrangement of esters of ortho-iodobenzyl alcohols proceeds smoothly to give isobenzofurans which can be intercepted in situ by inter- or intramolecular Diels-Alder reactions.An illustration of the usefulness of these reactions is the efficient synthesis of oestrone methyl ether and its 9p epimer (Scheme 18).'42 n BlLi Scheme 18 Aryl carbamates' 36 and phenyl tetramethyldiamid~phosphates'~~ also undergo anionic Fries rearrangements to give salicylamides and 2-hydroxyphosphonamide lJ4 P. Beak and D. J. Allen J. Am. Chem. Soc. 1992 114 3420. 135 S.0.de Silva J. N. Reed R. J. Billedeau X.Wang D.J. Norris and V. Snieckus Tetruhedron 1992 48 4863. 136 M. Tsukazaki and V. Snieckus Can. J. Chem. 1992 70 1487. 13' R. S.C. Lopes C.C. Lopes and C. H. Heathcock Tetrahedron Lett. 1992 33 6775. C. Quesnelle T. Ilhama T. Aubert H. Perrier and V. Snieckus. Tetrahedron Lett. 1992 33 2625. lJ9 A. J. Bridges A. L. Emmanuel C. Maduakor and C. E. Schwartz Tetrahedron Lett. 1992 33 7495. A. J. Bridges A. L. Emmanuel C. Maduakur and C.E. Schwartz Tetrahedron Lett. 1992 33 7499. 14' D. M. Giolando and K. Kirschbaum Synthesis 1992 451. 142 S. Horne and R. Rodrigo J. Chem. Soc.. Chem. Commun. 1992 164. L43 J.H. Nasman and N. Kopola Synth. Commun. 1992 22 2491. 158 A. P. Chorlton respectively. Protected derivatives of 3,4,5-trimethoxybenzaldehyde,when treated with alkali metals are subject to regioselective reductive elimination of the 4-methoxy The resulting anion can be quenched with a variety of electrophiles.An improved halogenation procedure has been developed for the preparation of l-halo-2,6-dimethoxybenzenes via the reaction of bis(2,6-dimethoxyphenol)dimethyl-tin and N-halogeno succinimides. '45 The palladium-catalysed coupling of aryl boronic acids has great utility in the synthesis of the unsymmetrical biphenyl natural products Biphenomcycin and Van~omycin'~~ and for the regio construction of tetraaryls quateraryls and higher order polyaryls. '47 An asymmetric variant of this reaction has been developed to give 4-aryl phenylalanines via cross coupling of aryl boronic acids and chiral tyrosine triflate.14' Suzuki has improved the original cross coupling reaction conditions thus allowing the synthesis of hindered biar~1s.l~~ Axially chiral biaryls have been obtained by the cross coupling of 2,6-disubstituted aryl Grignard reagents with chiral aryl-oxazolines. 50 Highly functionalized biaryls have also been synthesized via an intramolecular Ullmann coupling reaction directed by salicyl alcohol which acts as a tether between the two aryl moieties. After coupling the tether is removed by hydrolysis to furnish the biaryls. '' Palladium catalysed coupling of 1-iodo,-2,3-dimethylbenzene(35)gives 6H-dibenzo[b,d]pyrans (36)which results from coupling followed by a palladium catalysed CH-activation of the methoxy group.'" H3C0 ,0CH3 (35) Nio has been used for the first time for the cross-coupling of aryl carbamates and aryl triflates with Grignard reagents.' s3 The palladium-catalysed arylation of alkenes the Heck reaction is a powerful synthetic tool; its utility has been extended to the a-arylation of acyclic enol etherslS4 and the reaction can be asymmetrically catalysed with BINAP to give products with good enantiomeric purity.' s5 Two examples of homogeneous catalysis have been developed.These give advantages of higher activity and improved yields'56 and the 144 U. Azzena G. Melloni and A.M. Piroddi J. Ory. Chem. 1992 57 3101. 145 M. Wada H. Wakamuri A. Hiraiwa and T. Erabi Bull. Chern. SOC.Jpn. 1992 65 1389. 146 A. G. Brown M. J. Crimmin and P. D. Edwards J. Chem.SOC..Perkin Trans. I 1992 123. 14' C. M. Unrau M. G. Campbell and V. Snieckus Tetrahedron Lett. 1992 33 2773. 148 W.C. Shieh and J.A. Carlson J. Ory. Chem. 1992 57 379. T. Watanabe N. Miyaura and A. Suzuki SYNLETT 1992 207. 150 A. I. Meyers A. Meier and D. J. Rawson Tetrahedron Lett. 1992 33 853. 15' M. Takahashi Y. Moritani T. Ogiku H. Ohmizu K. Kondo and T. Iwasaki Tetrahedron Lett. 1992,33 5103. Is* G. Dyker Angew. Chem. Int. Ed. Engl. 1992 31 1023. S. Sengupta M. Leite D.S. Raslan C. Quesnelle and V. Snieckus J. Org. Chem. 1992 57 4066. W. Cabri I. Candiani A. Bedeschi and S. Penco J. Org. Chem. 1992 57 1481. 15' F. Ozawa A. Kubo and T. Hayashi Tetrahedron Lett. 1992 33 1485. lS6 J. P. Genet E. Blart and M. Savignac SYNLETT 1992 715. Aromatic Compounds ability to carry out the reaction in aqueous media.'" An unusual doubly substituted product has been obtained from the phase-transfer-catalysed Heck reaction of o-bromobenzaldehydes with methyl acrylate Scheme 19.It has been established that the bromine was replaced by the propionats group and the formyl group by the acrylate residue.' 58 Scheme 19 Aryl alkynes can be synthesized in good yields by the copper-catalysed coupling reaction of aryl halides with terminal alkynes.lS9 The a-and y-coupling reaction of allylic chlorides with p-methoxyphenylmagnesium bromide has been studied and it has been found that the solvent has a substantial bearing on the regio- and stereoselectivity of this reaction.16' Arylzinc reagents generated by electrochemical reduction of aryl halides have been found to be effective in the cross coupling of aryl halides.16' Electrosynthesis has also been successfully applied to the synthesis of unsymmetrical polyaryls.'62 Triarylbismuthines have been carbonylated for the first time by the use of rhodium (I) catalysts to give diarylketones. '63 Crossed carbonylation coupling has been achieved by the palladium-catalysed reaction of aryl fluorosilanes with aryl iodides. '64 Amides and azoles can be N-arylated with p-tolyllead tria~etate.'~'.'~~ Phenols can be oxidatively coupled with manganese (III) complexes.' 67 Acetal phenoxides also undergo oxidative coupling to afford 2,2'-dihydroxybiaryls with high regiochemical control.'68 Substitution via Aryl Radicals.-The rate constants of the intramolecular aryl radical cyclization of aldimines has been studied Scheme 20.It was found that there was a large preference for 6-end0 ring closure to carbon over 5-ex0 ring closure to nitrogen. This is in direct contrast to radical cyclization to alkenes. Energetic and steric postulates have been developed to explain these re~u1ts.l~~ The photostimulated reaction of 2-naphthoxide ions (37)with o-dihalobenzenes (38) in liquid ammonia gives the halosubstituted product (39) and the cyclized substituted 15' B. M. Choudary R. M. Sarrna and K. K. Rao Tetrahedron 1992 48 719. 15* S. K. Meegalla N. J. Taylor and R. Rodrigo J. Ory. Chem. 1992 57 2422. 159 K. Okaro M. Furaune M. Miura and M. Nornura Tetrahedron Lett. 1992 33 5363.160 N. H. J. Lajis and M. N. Khan Tetrahedron 1992 48 1109. 161 S. Sibille V. Ratovelornanana and J. Perichan J. Chem. SOC.,Chem. Commun. 1992 283. 162 P. Boy C. Cornbellas A. Thiebault. C. Arnatore and A. Jutand Tetrahedron Lett.. 1992 33 491. 163 C.S. Cho T. Ohe 0.Itoh and S. Uemura J. Chem. SOC.. Chem. Commun. 1992 453. 164 Y. Hatanaka S. Fukushirna and T. Hiyarna Tetrahedron 1992 48 21 13. 16' P. Lopez-Alvarado C. Avendano and J. C. Menendez Tetrahedron Lett. 1992 33 6875. P. Lopez-Alvarado C. Avendano and J. C. Menendez Tetrahedron Lett. 1992 33 659. 16' H. Nishino N. Itoh M. Nagashirna and K. Kurasawa Bull. Chem. SOC. Jpn. 1992 65 620. 168 G. Sartori R. Maggi F. Bigi A. Arienti and G. Casnati Tetrahedron Lett. 1992 33 2207. 169 M.J.Tornaszewski and J. Warkentin Tetrahedron Letr. 1992 33 2123. A. P. Chorlton Scheme 20 product (40).This is the first report of coupling of an aromatic radical with an oxygen nucleophile.' 70 It has been found that or-methyl styrene is hydrogenated by dihydroanthracene almost quantitatively at 280-310 "C in an uncatalysed H-transfer reaction. This reaction proceeds by a molecular formation of a radical by H transfer from a C-H bond.17' Aryl radicals generated from diazonium salts react with copper (11) p-diketones to give a-aryl-p-diketones in moderate yields.' 72 Flash vacuum pyrolysis of the alkyl esters (41) (X = 0 S CH,,CO) at 900°C gives dibenzofurans diben- zothiophenes fluorenes and fluorenones respectively as the major products. The mechanism involves the radical intermediate (42)which equilibrates by intramolecular hydrogen transfer via a six-membered transition state prior to cy~lization.'~~ 'x '-[O\,lo]- aco2-(41) (42) 5 Functional Group Interconversions of Benzene Derivatives Rapid reduction of nitroarenes to aromatic amines by sodium borohydride can be achieved by the enhancement of the catalytic activity of MOO with sodium ~e1enate.I~~ Sodium trimethylsilanethiolate has also been found to reduce nitroarenes to aromatic amine~.'~~ The reductive capability of sodium borohydride is also increased by the addition of nickel chloride; this system allows the facile deoxygenation M.T. Baumgartner A. B. Pierini and R. A. Ross Tetrahedron Lett. 1992 33 2323. I7l C.Ruchardt M. Gerst and M. Nolke Angew. Chem. Int. Ed. Engl. 1992 31 1523. 172 M. E. Llorus R. A. Abramovitch J. Marquet and M. Moreno-Manas Tetrahedron 1992.48 6909. 173 J. I.G. Cadogan H. S. Hutchison and H. McNab. Tetrahedron 1992 48 7747. 174 K. Yanada R. Yanada and H. Meguri Tetrahedron Lett. 1992 33 1463. 17' J.R. Huru F.F. Wong and M. Shiao J. Org. Chem. 1992 57 5254. Aromatic Compounds 161 of phenols.' 76 Aryl carboxylic acids can be reduced to benzyl alcohols with SmI and phosphoric acid.' 77 Zinc chlorochromate has been used as a mild inexpensive oxidant of benzylic carbon-hydrogen bonds.' ' Electron-rich aryl alkenes can be cleaved to aldehydes electrochemically. '79 This method should have environmental advantages over ozonolysis in large scale reactions.Methyl aromatic compounds have been photooxygenated in the presence of TiO and AgSO to give benzaldehydes and in some cases benzoic acids.'*' Aryl C-nitroso compounds can be conveniently synthesized by the pyridinium chlorochromate oxidation of hydroxylamines.' '' Two direct routes to the synthesis of aromatic nitriles via the aldehydes have been developed.' 82,183 6 Condensed Polycyclic Aromatic Compounds Methylene bridged polycyclic aromatic hydrocarbons (PAHs) are thought to be potential carcinogens. However few PAHs of this class have been synthesized. Harvey has synthesized a number of these PAHS'*~,~'~ and studied their electrophilic sub- stitution.lg6 Carbon-14 labelled dibenz[a,h]anthracene has been produced so that its biotransformations can be studied.IE7 Methyl substitution of the bay region of PAHs enhances their carcinogenicity.The trifluoromethyl analogue (43) of a potent carcin- ogen has been synthesized to examine its activity."* A number of carcinogenic nitro- nitroso- and amino-fluoranthenes have been prepared by standard methods. '89 Me0 0 + 40 0 (43) (45) Binaphthathiophene reacts with lithium to give 2,2'-disubstituted-l,1 -binaphthalene or dihydroperylene depending on the reaction condition^.^^' Both [5]-and [6]- helicenes (44) have been rapidly constructed via the Diels-Alder reaction of benzoquinone and the bis-enol ether (45).' ' 17' F. Wang K. Chiba and M. Tada J. Chem. Soc. Perkin Trans. 1 1992 1897. Y. Karnochi and T. Kudo Tetrahedron 1992 48 4303.H. Firouzabadi and A. Sharifi Synthesis 1992 999. 179 E. Steckhan and C. Kandzia SYNLETT 1992 139. E. Baciocchi G. C. Rosato C. Roi and G. V. Sebastiani Tetrahedron Lett. 1992 33 5437. la' W.W. Wood and J.A. Wilkin Syn. Commun. 1992 22 1683. la' H. Suzuki and C. Nakaya Synthesis 1992 641. la3 F. Delgao A. C. Cano 0.Garcia J. Alvarado L. Velasco C. Alvarez and R. H. Rudler Syn. Cornmun.. 1992 22 2125. C. Yang and R.G. Harvey Tetrahedron 1992 48 3735. C. Yang D.T.C. Yang and R.G. Harvey SYNLETT. 1992 799. E. Abu-shqara C. Yang and R.G. Harvey J. Org. Chem. 1992 57 3312. K. L. Platt and F. Setiabudi J. Chem. Soc. Perkin Trans. 1 1992 2005. '*' M. M. Coornbs and H. H. Zepik J. Chem. Soc. Chem. Cornmun. 1992 1376. C. J. van Haeringen N.F. Aten J. Cornelisse and J. Lugtenburg Recl. Trau. Chim. Pays-Bas 1992 111 335. I9O A. Dore S. Gladiali S. Cossu and 0.De Lucchi SYNLETT 1992 807. N. D. Willrnore L. Lui and T. J. Katz Anyew. Chem. Int. Ed. Engl. 1992 31 1093. A. P. Chorlton A domino-Heck coupling of aryl halides and dicyclopentadiene also demonstrates how simple precursors can be utilized to prepare PAHs Scheme 21.192 Triphenylene can be obtained in 66% yield from the decomposition of 1-fluoro-2-sodiobenzene ; this reaction is thought to proceed via trimerization of ben~yne.’~~ An improved procedure for the synthesis of several isomeric methoxy- nitronaphthalenes has been described.’94 Reagents i Pd(OAc), K,CO, Bu,NBr; ii I, hv; iii FVP 750°C Scheme 21 A convenient route to corannulene (46)has been developed flash vacuum pyrolysis of the fluoranthene (47)gives corannulene and its bromo derivative.The bowl to bowl inversion of corannulene dimethyl carbinol has been studied by examining the NMR of the coalescence of the diastereotopic methyl groups. From this data the barrier to bowl to bowl inversion was calculated to be G = 10 & 0.2 Kcal mol-’ at -64°C. This is remarkably close in energy to that for the conversion of cyclohexane from one chair form to the other.19’ Tetrabenzo[a,c,g,i]fluorenyl-17-methylurethane has been synthesized for use as a Nor protecting group. This group has been designed to allow adsorption onto porous graphitized carbon thus allowing facile separation of Nor-acetylated truncated peptides generated as impurities in solid phase peptide synthesis.’ 96 Angular phenylenes have been synthesized by a series of cobalt carbonyl mediated [2 + 2 + 21 cycloaddition reactions.The structures of these angular systems are best described by involving varying degrees of bond alternation. Thus (48) contains an internal ‘cyclohexatriene’ maximizing the ‘aromaticity’ of the flanking two benzene rings. Bond localization is attenuated along the series (48) (49) (50).197 K. Albrecht 0.Reiser M. Weber and A. de Meijere SYNLETT 1992 521. 193 M. Fossatelli and L. Brandsma Synthesis 1992 757. 194 C. Parkanyi H. L. Yuan A. Sappok-Stang A. R. Gutierrez and S. A. Lee Monatsh. Chem. 1992,123,637. 195 L.T. Scott M. M. Hashemi and M.S. Bratcher J. Am. Chem.SOC. 1992 114 1921. 196 R. Ramage and ?. Raphy Tetrahedron Lett. 1992 33 385. 19’ R. H. Schmidt-Radde and K.P.C. Vollhardt J. Am. Chem. SOC.,1992 114 9713. Aromatic Compounds 163 2,2'-Distyrylbiphenyl on electrochemical reduction undergoes [2 +21 cycloaddi- tion this result is compared with the photolytic [2 +21 cycl~addition.'~~~'~~ The formation of a great number of PAHs with up to a molecular weight of 604 occurs when an electric discharge from a graphite electrode is made in toluene.200 The fragmentation of PAHs observed in mass spectra supports the view that sufficiently large component PAHs probably survive in the diffuse interstellar medium.201 (48) n= 1 (49) n=2 (50) n =3 Non-benzenoid Aromatics.-Two new methods for the preparation of 1,6-meth- The ano[ lolannulene have been de~cribed.~'~.~'~ 1,6-methano[ lolannulene nucleus has also been used to demonstrate chirality due to deuterium substitution (+ )-l-(R)p-2,7-dideutero-1,6-methano[lO]annulene(51a) was prepared from the chiral dibromo-derivative (51b) by the formation of the lithio derivative followed by quenching with de~teriurn.~'~ The methanocycloundeca[6]pyrrole (52) has been synthesized and shown to be an aromatic molecule having a diatropic 14 n-electron system.205 X (51a) X = D (51b) X =Br Cyclopenta[a]azulenes (53) and (54) have been synthesized and fully characterized for the first time.The anions of these compounds (55) are not peripherally 14 n-conjugated because of the larger stabilization energy of the cyclopentadienyl anion compared to that of the azulene.206 19' A.Bohm K. Meeholz J. Heinze and K. Mullen J. Am. Chem. SOC. 1992 114 689. 199 A. Bohm and K. Mullen Tetrahedron Lett. 1992 33 611. 'O0 M.T. Beck Z. Dinya and S. Keki Tetrahedron 1992 48 4919. J. Aihara and H. Ichikawa Bull. Chem. SOC.Jpn. 1992 65 597. 'O' D. G. Barrett G. B. Liang and S. H. Gellman J. Am. Chem. SOC. 1992 114 6915. '03 R. Neidlein and G. Schroder Chem. Ber. 1992 125 2225. '04 A. Meyer and K. Schogl Monatsh. Chem. 1992 123 465. '05 N. Kanomata K. Kamae Y. Iino and M. Nitta J. Org. Chem. 1992 57 5313. '06 Y. Kitamuri M. Yasunami T. Hioki I. Kikuchi and K. Takase Bull. Chem. SOC.Jpn. 1992 65 1527. 164 A. P. Chorlton Allylic dihydroazulene (56) rearranges at room temperature to the thermodynami- cally more stable substituted azulene (57).This novel Cope-type rearrangement can be observed by the naked eye as a colour change from yellow to blue.207 The [abcl-annelation of naphthalene or phenanthrene systems has given the [18lannulene (58). This molecule is essentially non-planar consisting of 'aromatic islands' which are connected by (E)-configured alkene bridges. The absence of a diamagnetic ring current rules out a macrocyclic aromaticity.208 The reductive alkylation of the pyrene isomer (59) afforded the bridged [14]- annulene (60). This reaction has been demonstrated to take place via an electron- transfer mechanism. O9 p2-2 \ \ (56) Yellow (57) Blue ii RX (59) (60) 7 Cyclophanes Medium-sized cyclophanes have been found to undergo novel isomerization and transannular cyclization reactions.* An example of this is the iron catalysed bromination of the metacyclophane (61) which affords the corresponding tetrahydro- pyrenes oia an addition-elimination reaction." * '07 K.Hafner J. Hartung and C. Syren Tetrahedron 1992 48 4879. '08 H. Meier H. Kretzschmann and H. Kolshorn J. Org. Chem. 1992 57 6847. '09 K. Mullen J. Alexander K. U. Klabunde F. Klarner H. Lund and T. Lund Chem. Ber. 1992 125,505. 210 T. Yamato J. Matsumoto K. Tokuhisa K. Tsuji K. Suehiro,and M. Tashiro,J. Chem.SOC.,Perkin Trans. I 1992 2675. 'I1 T.Yamato J. Matsumoto K. Tokuhisa K. Suehiro and M. Tashiro,J. Chem.SOC.,Chem.Commun. 1992 865. T. Yamato J. Matsumoto,K.Tokuhisa M. Shigekui K. Suehiro,and M. Tashiro,J. Org.Chem.,1992,57 395. Aromatic Compounds Et Et + Generally cyclophanes are not prepared by direct annulation of the bridge but by ring contraction rearrangement of bridges or formation of the benzene ring in the final step. Tris(donor)-substituted 1,3,5-trinitrobenzenes generally exist in boat or twist boat conformations. This distortion has been put to good effect in the synthesis of cyclophane (62). Reduction of the nitro group in (63)eliminates the electronic bias for a boat conformation and this results in the benzene ring returning to planarity.213 The X-ray analysis of the biphenylene-cyclophane (64) illustrates how the frame- work of the biphenylene unit is bent out of plane.This distortion is caused by transannular repulsion.2 l4 (62) X=NH2 (63) X=NO2 'I3 J.J. Wolff S. F. Nelson D. R. Powell and B. Nuber Angew. Chern.. Inr. Ed. Engl. 1992 31. 882. '14 K. Saitmacher J. E. Schulz M. Nieger and F. Voglte J. Chem. SOC..Chem. Commun.. 1992 175.