6 Aromatic Compounds By A. P.CHORLTON ZENECA Specialties Hexagon House. Bla~kley,Manchester M9 3DA. UK 1 General and Theoredcal Studim [1,2-13C2]Benzene autornerizes at high temperature to give a 1,2 :1,3:1,4 product ratio of 72 :24 :4. Four plausible mechanisms to explain this have been put forward the 1,Zcarbon shift mechanism; the dyotropic shift mechanism; the benzvalene mechan- ism; and the 1,Zhydrogen shift mechanism. High-level ab Wtiocalculations have been reported that favour the 1,Zhydrogenshift process.' The photochemistry of S and S benzene involves the production of benzvaiene and Dewar benzene respectively. An MC-SCF study of these processes indicatesthat the products of benzene photochemis- try appear to be controiled by the topology of the S,/S Grassing surface.2 The X-ray crystal structure and photoelectron spectrum of 3,3'-bicyclopropnyl (1 one of the four valence isomers of benzene,has been determined.The photoelectron spectrum of (I) can be interpreted in terms of about a 2 :1 mixture of anti and gauche conformers respectively in the gas phase whereas the X-ray crystal structure of (1) is only present in the anti form.3 Zirconocene complexes of the highly strained isomers of benzene I,2,3-cyclohexa-triene (2) and cyclohexen-3-yne (3) have been synthesized? A new multiphoton fragmentation of benzene at 193 nm has been proposed to proceed via the intermediate triplet states and neutral fragments such as C,H,.5 Squires and coworkers have reported values for the heats of formation of 0-,m-,and p-benzynes based on energy-resolved collision-induced dissociation measurements.The CI calculations carried out independently by the groups of Squires and Borden gave good agreement ' K.M.Men and L.T. Scott J. Chem. SOC.,Chem. Cornmun. 1993 412. I. J. Palmer I.N. Ragazos F. Bernardi M. Olivucci and M. A. Robb J. Am.Chem. Soc. 1993 115,673. R. Boese D. Blaser R.Gleiter K. W.Pfeifer W. E.BiIlups and M. M.Haley J. Am. Chem.Soc. 1993,i15 743. 'J. Yin K.A. Abboud and W.M. Jones J. Am Chem. SOC. 1993 115,8859. Y.Mori and T. Kitagawa Bull. Ckem. SUC.Jpn. 1993.66 1043. 145 A. P. Churlton with the experimental results for the heats of formation of o-benzyne but find that the experimental results for m-and p-benzyne are too Photolysis of benzocyc-lobutenedione (4) gives o-benzyne via the intermediacy of the bisketene (5).Exarnin-ation of this process in an argon matrix shows that (5) and (4) can interconvert thermally or photochemically several times before significant photochemical decar- bonylation to o-benzyne occurs.* Evidence has been presented for the presence of a halide-benzyne complex in the gas phase.' The generation of arynes in the gas phase has been reviewed." The role of delocalization in benzene has been the subject of debate; ab initio SCF caIculations have shown that it is misleading tojudge the nature ofdelocalization based on a 0-zpartition.It was therefore conciuded that delocalization effects act to stabilize strongIy symmetric benzene in accord with concepts ofclassical resonance theory.' l Classical valence bond theory has also been applied using quantitative resonance theory (QRT) to access the It-electron transfer in substituted benzenes.These QRT calculations areinagreementwith thoseobtained viaabinitio MO theory." Messmer hascuncluded based on energetic considerations that the phenomenon of resonance in the cIassica1 valence bond sense is best described by a bent-bond model.' The results of these cal-culations indicate that the benzenoid isomer (6)is preferred over the quinoid form (7).14 The structure of 1,3,5-triamino-2,4,6-trinitrubenzene (8) and a number of related compounds have been studied using ab initio Hartree-Fock and local density functional computational methods. These calculations predict a planar structure in accord with an X-ray crystallographic study; this is a contradiction to semiempirical data which predict (8)to be in the boat conformation.The planarity of (8)is thought to be due to hydrogen bonding of the flanking groups.' 'Hall hasargued that when a benzene ring is S.U. Wierschke J.J. Nash and R.R. Squires J. Am.Chem. Soc. 1993,115,11950. ' A. Nicolaides and W.T. Borden J. Am. Chem. Soc. 1993 115 If 951. a T.Mosandl and C. Wentrup J. Org. Chem. 1993,58 747. H.V. Linnert and J. M.Riveros J-Chem. Soc. Chem. Commun. f993,48. R.F.C. Brown and F.W. Eastwood SYNLETT 1993,9. I' E. D.Glending,R. Faust,A. Streitwieser,K. P.C.VoIlhardt,andF. Weinhold,J. Am. Chem.Soc.,1993,115 10952. l2 Y.Pipeng J. Gem. Res. (S) 1993,368. P.A. Schultz and R.P.Messmer J. Am. Chem. Soc. 1993 115 10943. J. M. SchuIman and R.L. Dish J. Am. Ckm. Soc. 1993 115 11 153. K. K. Baldridge and J.S. Siegel J. Am. Chem. Soc. 1993 115 10782. Aromatic Compounds (9) (lo) X = H; Y = H. (111 X = H;Y = Br. (12) X=Br;V=Br. present as an embedded component in a molecule e-g. (9) then the adoption by the benzene ring of the boat form requires the least en erg^.'^ X-Ray crystalIographic and dynamic 'H NMR spectroscopy of 2,3,6,7-tetrab- romo-l,4,5,8-tetramethylnaphthalene(1O)and its bromo derivatives (1I)and (12)show that these compounds have severely distorted naphthalene nuclei in the solid state. In solution this corresponds to conformations that can have an appreciable barrier to conversion(AG*=t 16 Kcal mol- ') which occurs by both rotation and flipping of the peri-substituents.' The rotation of the peri positions in 1-t-butyl-8-fluoronaphthalene has also kn studied by dynamicNMR.The barrier to rotation of the t-butyt group has been calculated'* at AG* 11 8.6 Kcal mol- I. In a similar study the barrier for the E-2 interconversionof atropisomers of naphthyl- 1-sulfones having a methyl group at the 2-position has been measured and found to cover the range 10.6-18.4Kcal mol -'.Low temperature chiral resolution allowed the separation of the two enantiomeric forms and their associated atropisomers.' The restricted rotation in 1&diarylnaphthalenes (13) has been used to probe the interactions between x-stacked dimers of benzenes. The attractiveor repulsiveforces between the benzenes should give rise to a higher or lower energy barrier to rotation respectively.The barrier to rotation was found to increase linearly with the increasing electron-withdrawing capacity of the X and Y groups. No extra increase in the rotation barrier was noted when X = OMe and Y = NO,. These observations point to the domination of polar/lt over charge-transfer effects in the interaction of stacked benzene rings." XY Is G.G. HaH J. Chent. Soc. Perkin Trans.2 1993 1491. *' P.R. Ashton G.R. Brown A.J. Foubister D. R. Smith N. Spencer J. F. Stoddart and D.J. Williams Tetrahedron Lett. f993 34 8333. G.W. Gnbble and E. R. Olson J. Org. Chem. 1993,58 1631. j9 D. Casarini E. Forsti F. Gasparrini L.Lunazzi D. Macciantelli D.Misiti and C. Villani J. Org. Chem. 1993,58 5674. F. Cozzi M. Cinquini R. Annunziata and J. S. Siegel J. Am.Chem. Soc. 1993 115 5330. A. P. Ckorlton The aromaticity or lack of it in c, is a contentious issue. Fowler has put forward qualitative symmetry arguments with evidence from bond lengths and energies and from the addition chemistry of C60,which point to a localized description of the 7~ system in this molecule. Regioselective saturation ofsix double bonds in C, is predicted to give the 48 electron aromatic system (14).” It has been postdated that large polycyclic conjugated rings such as kekulene (15) with an internal cavity may exhibit superaromaticity. A general graph theory of superaromaticity has been developed to analyse this phenomenon.The results of this work indicate that these systems are essentially non-superaromatic.” The ESR spectrum of a non-Kekule polynuclear aromatic has been reported for the first time; trioxytriannufene (15) is a remarkably stable triplet biradi~al.~~ Full characterization of the disjointed non-Kekule singlet hydrocarbon I ,2,4,5-tet-rarnethylenebenzene biradical (17) has been completed.24 Contrary to previous results it has been established by theoretical methods that 1,4-bishomotrupylium cation (18) rather than the cis-8,9-dihydro-l-indenyl cation (19) corresponds to the minimum energy structure. These calculations however are not sensitive enough to confirm the homoaromatic character of (18).” Homoaromaticity has been tentatively ascribed to the stabilization shown by arene oxides on their acid-catalysed aromatization.26 -5 7 2 Preparation of Benzenes from Non-aromatic Precursors The Bergman cydization the thermal rearrangement of conjugated cis-enediynes to P.W. Fowler D. J. ColIins and S. J. Austin J. Chem. Soc. Perkin Trans. 2 1993 275. l2 J. Aihara Bull. Chem. SOC.Jpn. 1993,66,57. 23 G.A. Allinson R. J. Bushby and 3.L. Paillaud J. Am. Chem. SOC. 1993 115 2062. 24 J. H. ReynoIds J. A. Berson,K. K. Kumashiro,J.C. Duchamp K.W. ZiIm J. C. Scaiano A. B. Berinstain A. Rubella and P. Vogel,J. Am. Chem. Soc. 1993,115 8073. ” D. Crerner P. Svensson E. Kraka 2. Konkoti,and P. AhIberg J. Am. Chem. SOC. 1993 115 7457. ’‘ S. Nagaraja Rao R.A. M. O’FerralI S. C. Kelly D. R. Boyd,and R.Agarwal J. Am. Chem.SOC.,1993,115 5458. Aromatic Compounds 1,4-benzenoid diradicals continues to be ofimmense The incorporation of the cis-enediyne in the synthesis of naturally occurring antitumour antibiotics represents the major challenge. This has been achieved by Nicolaou who has reported the first synthesis of ~aIichearnicin.~~-~~ Successful model studies towards the synthesis of dynemicin have also been ~ornpleted.”~~~ Magriotis has developed a tandem Claisen-Bergman strategy fur the stereocontrolled synthesis of tetrahydronaphtha-lenes (Scheme l).32 tO2TIPS Reagents i LHMDS THF,-78“C,TlPSOTf Scheme 1 Grissom has demonstrated that enediynes (20) possessing tethered olefin radicaI acceptors can participate in tandem enediyne-radical cyclizations to yield dihydroben- zindenes (21) (Scheme 2).33-35 Meyers has shown that 1,Qdidehydro[ 1Olannulene (22) undergoes a rapid cydiz- ation to form the biradical 1,5-dehydronaphthalene (23).36In a similar study Toshirna has cyclized the enyne-alIene sulfides (24) and sulfones (25).37*38 27 R.Gleiter and d. Katz AnQew. Chem. Int. Ed. Engl. 1993,32,842. K.C. Nicolaou C. W. Hummtl M.Nakada K. Shibayama E. N.Pitsinas H. Saimoto Y.Mizuno,K. U. Batdenius and A. L. Smith J. Am. Chem. Soc. 1993,115,7625. 29 K. C.Nicolaou Angew. Chem. Inr. Ed. Engi. 1993,32,1377. K. C. Nicolaou W. M. Dai Y,P. Hong,S.C. Tsay K. K. Baldridge and J. S. Siegal J. Am. Chem. SOC. I993,115,7944. 3’ P.A. Wendtr C. K.Zerchtr S. Beckham and E. M. Haubold J.Org. Chem. 1993,58,5867. 32 P.A.Magriotis and K.D. Kim J. Am. Chem. Soc. 1993,115,2972. 33 J. W.Grissom and T. L. CaIkins. 1.Org. Chem. 1993.58 5422. 34 J-W. Grissom,T. L. Calkins and H. A. McMillen J. Org. Chem. 1993,58 6556. 35 J. W. Grissom T. LaCalkins and M. Egan J. Am. Chern. SOC. 1993 115,11 744. 36 A.G.Myers and P. S. Dragovich J. Am. Chem. Soc. 1993,115 115 7021. 37 K.Toshima K. Ohta A. Ohashi T. Nakamura M. Nakata and S. Matsumura J. Chem. SOC.,Chem. Comun, 1993,1525. 38 K. Toshima K. Ohta A. Ohtsuka S. Matsumura and M. Nakata J. Chern. SOC.,Chem. Commun. 1993 1406. A. P. Chorlton Reagents i PhCI cyclohexa-l+diene 19O"C,2.5br (96%) Scheme 2 OH CH&CCHpS OR OR I (24) X = S (25) x = sop This approach has also been utilized by a number of workers to investigate the enyneC3lcumulene cyclization of neocarzinostatin (26) (Scheme 3).39-42 Padwa in an investigation of the decomposition of o-alkynyl substituted aryl diazo ketones (27) has proposed that the intermediate aryl ketene (28) cycIizes in a Meyers-type process to give the diradical (29) which on quenching gives the 8-naphthol (3U).43 The synthesis of benzene rings via Fischer carbene complexes continues to be widely utilized.Wulff and coworkers have carried out an in-depth study into this reactionq4 The results of these experiments suggest that phenol (31) arises from a vinyl carbene cornplexed intermediate (32) and that phenol (33) and cyclopentenedione (34) arise 39 S. W. Scheuplein R.Machinek J. SuEert and R. BNCkner Tetrahedron Lett. 1993,34 6549. 40 T. Takahashi H. Tanaka Y. Hira T. Doi H. Yamada T.Shiraki and Y. Sugiura Angew. Chem. Int. Ed. Engl. 1993,32 1657. 41 M.Tokuda K. Fujiwara T. Gomibuchi and M. Hirama Tetrahedron htt. 1993,34 669. 42 K.-I. Yoshida Y. Minami R Azuma M.Sacki and T. Otani Tetrahedron Lett. I993 34 2637. 43 A. Padwa U. Chiacchio D.J. Fairfax,3. M. Kassir A. Litrico M. A. Scmones and S.L.Xu 1.Org. Chem. 1993,58 6429. 44 B.A. Anderson J. Bao T.A. Brandvold C. A. Challener W.D. Wulff,Y.-C. Xu and A. L. Rheingold J. Am. Chem. Soc. 1993,115 10671. Aromatic Compounds Scheme 3 from a vinyl ketone complexed intermediate (35). The product distribution of these products is discussed with reIation to solvent concentration and nature of metal (Scheme 4).In another study Thomas and coworkers have synthesized metal complexed vinyl ketenes of the type (35) and have shown that their reaction with aIkynes leads to phenols (33) if the R group is eIectron donating whereas if this substituent is electron withdrawing cycIopentenediones (34) are f~rmed?~.~‘ Differentially protected hydroquinone-(tricarbony1)chromium complexes (36)can be prepared directly from alkenyl and alkynyl Fischer carbene complexes by interception with a variety of electrophile~.~~ The first example of bemannulation of alkynes with iron@) carbene complexes has been reported. Furan annulation is a competing process in this reaction.48 The reaction of carbenexhromium complex (37) with isocyanides provides a mild and regiospecific access to aromatic amines Is K.G.Moms S. P. Saberi M. Salter S. E. Thomas M. F. Ward A.M. Z. Slawin and D. J. Williams Tetrahedron,1993 49 5617. 46 K.G.Morris,S. P. Saberi and S.E. Thomas J. Chem. Soc. Chem. Commun. 1993 209. S. Chamberlain W.D.Wulff and B. Bax Tetrahedron,1993,49 5531. ’’ Atta-ur-Rahmann,W. F. K. Schnatter and N. ManoIache J. Am. Chem. Soc. 1993 115 9848. A9 R. Aumann Chem. Bet. 1993,126 1867. A. P.Chorlton OH R2 I t Hi (33) ONrnY-6 R’ Cr(CO) (35) Reagents i R’CZCH; ii RZCECH,CO scheme 4 o-Amino phenols (39) can also be prepared via the photocyclizationof aminocar-bene-chromium complex (40).50 A similar process utilizing the methoxycar-bene-chromium complex (41) furnishes the annulated catechol (42).’ (40)X=NHR (39)X=NHR (41) X=OMe (42)x=o C.A.Medic D. Xu and B.G.Gladstone J. Org. Chem. 1993,58,538. 5r C.A. Medic and W.M.Roberts Tetrahedron Lett. 1993 34,7379. Aromatic Compounds Catechols have also been synthesized by the ruthenium-catalysed reaction of 176-diynes with carbon monoxide. This transformation is unique in that it represents a rare example of catalytic incorporation of carbon monoxide into a diyne. Also it exhibits a new mode of successive incorporation of two molecules of carbon monoxide (Scheme 5).52 ‘)(: E OTBDMS + TBDMSH + CO --E OTBDMS E= COzEt Scheme 5 An alternative regiocontrolled synthesis of substituted catechols has been develop- ed the products from conjugate addition of vinyl copper reagents to cyc-lobutenediones when subjected to thermal rearrangement yield catechols (Scheme OH Scheme 5 @-fS, a similar process addition of stannylquinones to 4-chlorocycIobutenones followed by thermal rearrangement gives substituted naphthoquinones and anthra- quinone~.~~ Liebeskind has developed a general regioselective synthesis of substituted benzocy- clobutenedione monoacetais.These reagents can function as important intermedi- ates in the regioselective synthesis of phenols. 3-Alkylidene-4-allenylcyclobutenes undergo thermal ring expansion to give o-quinodimethanes which upon eiectrocyclic ring closure give benzocyclobutenes (Scheme 7).56 o-Quinodimethanes are of synthetic utility as effective dienes in DieIs-Alder reactions fur the construction of polycycIic aromatics.A number of novel methods have been developed for the generation of o-quinodimethanes (Scheme 7).57-59 Benzyne and benzoquinone have been used effectively as 2n components in Diels-Alder reactions to prepare 1,4-naphthoq~inones.~~~~~ Negishi has developed a ” N. Chatani Y. Fukumoto T. Ida and S. Murai J. Am. Chem. Soc. 1993,115,11 614. ” A. Gurski and L. S. Liebskind J. Am. Chem. SOC. 1993,115,6101. ” J. P.Edwards D.J. Krysan and L.S. Liebeskind J.Am. Chem. Soc. 1993,115,9868. ” J. P.Edwards D.J. Krysan,and L,S. Liebeskind J. Org. Chem. 1993 58 3942. ’’ J-E. Ezcurra and H.W. Moore Tetrahedron Lett. I993,34,6177. 57 S.H. Woo Tetrahedron Lett. 1993,34,7587. ’’ H.Fujihara M. Yak and N.Furukawa J. Org. Chem. 1993,58 5291. 59 G.Kanai N. Miyaura and A. Suzuki Chem. Lett. 1993 845. A. P. Chorlton Reagents i A or hv; ii E*; iii hv scbeme 7 selective synthesis of benzene derivatives via palfadium-catalysed carbometdlation of alkynes (Scheme 8).62 Ph Reagents i R'CECR' 5% PdL, NEt, DMF Scheme 8 The intramolecular Michael-Aldol process has been used in the synthesis of the hexasubstituted aromatic ring present in a key intermediate for the synthesis of pseudopterosin A.63 Naphthopyrans have been synthesized from a 14-membered pdyketide lactone by the intramolecular aldol process.64 Salicylates have been prepared by themolytic ring closure of prop-1-en-1-yI substituted malonates (Scheme 9).65 M.A. Brimble and S.J. Phythia Tetrrihedron Lett. 1993 34 5813. 61 V.I. Hugo,P.W. Snijman ai,d I. R. Green Synth. Commun. 1993 23 577. E.Negishi M.Ay,and T. Sugihara Tetrahedron 1993,49 5471. 63 M.E. Jung and C.S.Siedem J. Am. Chem. Soc. 1993,115 3822. 64 K.Tatsuta Tetrahedron Lett. 1993 34 4961. 65 0.E.O. Homi and L. Hirvela Tetrahedron Lett. 1993,34,6463. Aromatic Compounds Frost has made progress in the identification and removal of impediments to the biocatalytic synthesis of aromatics from gIu~ose.~~ 3 Non-aromatic Compounds from Benzene Precursors Intramolecular anodic oxidation of phenols (43) leads preferentially to spirodienones (44);a competing reaction gives the methanol adduct (45). Swenton has examined the process and has shown that the product ratio is dramatically affected by the olefin structure.67 A versatile route to quinone N-acylimine ketaIs (46) from p-methoxyanil- ides has been developed utilizing anodic oxidative technol~gy.~~.~~ Anodic oxidation of 3,5-dihalogenotyrosines (47) gives a cavernicolin model compound (48).All four possible stereoisomers were formed but this was due to the special characteristics of (48) rather than the method~logy.~~ Similar intramolecular oxidative processes using hypervalent iodine have been effected to obtain the key intermediate (49) in the total and partiaI synthesis of aranorosin (50);the model compound (511 an intermediate towards the synthesis of marine metabolites such as aerothionin has been synthesized by these methods -73 A study of phenolic oxidation using phenyliodonium diacetate has also been carried " K.A. Dell and J. W. Frost,J. Am. Chem. Soc. 1993.115 11 581. 67 J.S. Swenton K. Carpenter Y. Chen M. L. Kerns and G.W. Morrow,J. Org. Chem. 1993.58 3308. J.S. Swenton T. N. Biggs and W. M. CIark J. Org. Chem. 1993 SS 5607. b9 M.Novak,J. S. Hehick N.Oberlies K.S. Rangappa,W. M.Clark and J. S. Swenton,J. Org. Chem.,1993 58 867. '* M. Cavazza,G. Guella L. Nu& F. Pergola N. Biahicrini and F. Pietra J. Chem. Soc. Perkin Trans. 2 1993,3117. 71 A. McKillop L.McLaren R.J. Watson R. J. K. Taylor and N.Lewis TetrahedronLett. 1993,34,5519. '' P. Wipf and Y. Kim J. Org. Chem. 1993,58 1649. 73 M. Kacan D. Koyuncu and A. McKilIop J. Chem. Soc. Perkin Trans. I 1993 1771.'' A. Pclter and S.M. A. Elgendy J. Chem. SOC. Perkin Trans. 1 1993 1891. A. P. Chorlton Microbial oxidation of benzenes to cis-cyclohexa-3,5-diene diols has been used as the key transformation in the synthesis of inositol stereoisomers and deuteriated conduritol derivative^.^^.^^ The bacterial degradation of aromatic compounds has been discussed. ' The mechanism of ceric ion oxidation of naphthalene to naphthoquin-1 +one has been in~estigated.~' This oxidation can also be achieved with hydrogen peroxide catalysed by hexafluoroacetone hydrate. 79 The oxidation ofhydroquinones to quinones can be effected in the solid state with cerric ammonium nitrate.80 Hydroxyaromatics can be oxidatively cleaved with superoxide to aromatic 1,2-dicarboxylic acids." Electrochemical reduction of phthalic acids gives 1,2-dihydrophthalic acids which have been used as diene components in synthesis.82 The reduction of disubstituted naphthalene derivatives by potassium-graphite intercalate C,K has been reported.The C,K-ether system may be an alternative to Birch-type reaction^.'^ Oxazo-line-mediated 1,S-nucleophilic addition to aromatic rings has continued to be utilized by Meyers as in the key step in the synthesis of the phytoalexin lancinilene (Scheme Reagents i (CH,CHCH,SiMe,)Li; ii Me1 Scheme 10 75 H. A.J. Carless K. Busia and U.Z. Oak SYNLETT 1993 672. 76 H.A. J. Carless K. Busia Y. Dove and S. S. MaIik J. Chem. SOC.,Perkin Trans.I. 1993,2505. 77 G. Gottschalk and H.-J. Knackmuss Angew.Chem. In[. Ed. Engl. 1993,32,1398. " M.V.Bhatt and M. Periasamy J. Chem. SOC.,Perkin Trans.2 1993,1811. 79 W. Adam and P. A. Ganeshpure Synthesis 1993 281. J. Morey and J. M. Saa Tetrahedron 1993 49 105. W. Li C. Sotiriou-Leventis M. Saha P. P,Fu and R.W. Giese Synth. Commun. 1993 23,97. '* T. Ohno M. Ozaki A. Inagaki T. Hirashima and 1. Nishiguchi TetrahedronLett. 1993 34,2629. 83 I.S.Weitz and M. Rabinovitz J. Chem. SOC., Perkin Trans.1 1993 117. 84 T.G. Grant and A.I. Meyers Tetrahedron Lett. 1993 34,3707. Aromatic Compounds Chiral oxazolines have been prepared from (S)-serine; these chiral auxiliaries show favourable asymmetric induction in a process similar to Scheme Tomioka has employed 2,6-di-t-butyl-4-methoxyphenyIesters (52) as an effective inert electron deficient moiety to facilitate i,6nucleophilic additionto aromatic rings.Incorporation of the chiraf diether (53)in this process affords adducts (54) in high e.e.86 OMe I”! st;”* (54) (53) The reaction mode and selectivity and regoselectivity of the photocycloaddition of 2,3-dirnethylbuta- 1,3-diene (DMBD)and benzene are markedly dependent on the arene substituent.Ingenera1,mixturesofproductsareformed.Thisisinmarkedcontrastto the photoreaction of DMBD and benzonitrile which gives the (4 + 4) photocycloadduct (55) as the major product (Scheme 11).87 Scheme 11 The stereoselectivity of the intramolecular (2 + 2) photocycloaddition to benzenes A.I. Meyers W. Schmidt and M. J. McKennon Synthesis 1993 251. 86 K. Tomioka M.Shindo and K. Koga Tetruhedron Lett. 1993,34,681. ” A. Gilbert and 0.Griffiths J. Chem. Soc. Ferkin Trans. I 1993 1379. A. P.Choriton has been examined.88 A diastereoselective(4 + 2) cycloadditionof singlet oxygen has been observed in the photooxygenation of a chid naphthyl aIcohoi (56) (Scheme 12). These results indicate that the chiral alcohol directs the incoming singIet oxygen.89 R'OYo* R'yoR2 Reagents 0,,TPP hv CDCI, rt Scheme 12 4 Substitution in the Benzene Ring Electrophilic Substitution.-Simple methods to prepare polyiodinated arenes are scarce. Barluenga has developed a method using bis(pyridine)iodonium(I)tetraborate that allows easy access to these iodobenzene derivative^.^' The introduction of iodine into polyalkylbenzenes has also been achieved using N-iodosuccinimide and acidic catalysis?' DiaryIiodonium salts (Ar,I)+X are a very important class of polyvalent iodine compounds.They are generally synthesized indirectly uiaary1 iodides. However by the use of iodofluorosulfate they can be obtained directly from aromatic compounds under mild condition^.^' ips0 substitution of sulfonyl chlorides and of the trimethyl- silyl group with iodine is an excellent regiospecific method for the preparation of aryl iodides.93-95 A number of more selective procedures for introducing bromine into aromatic arnines and phenols have been developed These include the use of hexamethylene tetraamine tribromide pyridinium hydrobromide and N-bromosuccinimide in the presence of primary or secondary arnine~.~~-~~ Bromination of deactivated aromatics has been achieved using bromine trifluoride without the use of a cataIysLg9 A facile conversion of arenediazonium saIts into arylfluorides using boron trifluoride etherate as a solvent has been developed.'00 Arylfluorides can also be obtained regioselectively by the rapid fluorodesilylation of aryltrimethylsilanes using xenon difluoride.lo' '* P.J. Wagner and K. Cheng Tetrahedron Lett. 1993,34,907. 89 W. Adam and M. Prein J. Am. Chem. SOC.,1993 115 3766. '* J. Barluenga J. M.Conzalez M. A. Garcia-Martin and P.J.Campus Tetrahedron Lett. 1993,34,3893. '' P.Bovonsombat and E. McNelis Synthesis 1993,237. 92 N. S.Zefirov T. M. Kasumov A.S. Komin V.D. Sorokin,P. J. Stang and V.V. Zhdankin Synthesis 1993 1209.93 T. Satoh K. Itoh M. Miura and M. Nomura Bull. Chem. Sac Jpn. 1993 66 2121. 91 B. Bennetau and J. Dunogues SYNLETT 1993 171. '' L.A. Jacob 3.-L. Chem and D. Stec Synthesis 1993,611. 96 S. Fujisaka H. Eguch A. Omura A. Okamoto and A. Nishidas Bd. Chem. Soc. Jpn. 1993,66 1576. 97 W. P.Reeves and R. M. King 11 Synth. Commun. 1993 23 855. 98 S.C. Bisarya and R. Rao Syrtth. Conunun. 1993 23 779. 99 S. Rozen and 0.Lerman J. Org. Chem. 1993,58 239. loo K. Shinhama S. Aki T. Farata and 3.-I. Minamikawa Synth. Commun.,1993 23 1577. A.P. Lothian and C.A. Ramsden SYNLETT 1993 753. Aromatic Compounds In the presence of ozone nitrogen dioxide exhibits strong nitrating abilities for alkylbenzenes at low temperature converting them into the corresponding nitro derivatives in high yie1ds.lo2 Use of this nitrating agent on alkyl aryl ketones gives high levels of orthosubstitution along with the meta isomer.This is in contrast to traditional nitrating procedures which lead predominantly to meta sub~titution.'~~ The use of calcium nitrate for the nitration of phenols has been studied. O4 An improved procedure for the nitration of benzocylobutene has been developed usingacetyl nitrate generated in situ by a continuous process in the presence of rnontmorillonite K10 clay."' Work has continued to render the Friedel-Crafts reaction truly catalytic. The Friedelxrafts acylation is generally achieved using a stoichiometric amount of aluminium chloride as a Lewis acid catalyst. This can be problematical on a large scale because the aluminium chloride cannot be reused because of its solubility in the aqueous workup.This problem has been addressed by a number of workers. Friedel-Crafts acylation proceeds smoothly using a catalytic amount of lanthanide triflate which can be recovered and reused.'06 The Friedel-Crafts acyIation can also be carried out in the absence of catalyst using a mixed anhydride. These are prepared by the reaction of a carboxylic acid with trifluoroacetic anhydride in the presence of phosphoric acid or active silicon(1v) catalyst^.^^^^'^^ K10 montmorillonite on its own and impregnated with zinc chloride (clayzic) and other solid acid catalysts have been used for Friedel-Crafts aIkylation~.'~~ These catalysts have a similar activity to aluminium chloride but can be used in smaller quantities and reused.The mild conditions for these catalysts has the added advantage over aluminium chloride that alkyl substituted aromatics can be prepared by the reaction of arenes with allyl alcohol without isomerization ofthe allyl double bond.'" Reduced and reversed reactivity has been observed in the Friedel-Crafts alkylation with clays due to differential adsorption of the reactants onto the solid surface. -I4 The Fries rearrangement of phenyl acetate to ortho-hydroxyacetophenoneis mare selective in the presence of zeolite GaZSM-5." Investigations into the mechanism of the Fries rearrangement in polyphosphoric acid have suggested an intermolecular process.' l6 The amino-Claisen rearrangement can be effected at less severe con- ditions than the thermal process by Lewis acid catalysts.117v11e The synthetic utility of the Friedel-Crafts reaction has been increased by a number of modifications.A gallium dichloride-mediated reductive Friedel-Crafts reaction has been developed Io2 H.Suzuki T. Murashima I. Kogai and T. Mori J. Chem. Suc. Perkin Tram. I 1993 1591. Io3 H. Suzuki T.Murashima A. Tatsurni and I. Kozai Chem. Lett. 1993 1421. Io4 S. C. Bisarya S. K. Joshi and A.G. Holkar,Synth. Commun. 1993 23 1125. lo'P.J. Thomas and R.G.Pews Synth. Comun. 1993 W 505. A. Kawada S. Mitamura and S. Kobayashi J. Chem. Soc. Chem. Commun. 1993 1157. Io7 K. Suzuki,H. Kitagawa and T.Mukaiyama BuU. Chem SOC.Jpn. 1993,66 3729. I*' C. Galli and S. Fornarini J.Chem. SOL Perkin Trans. 2 1993 1147. Io9 0.Sieskind and P. AIbrecht Terrahedroon Lett. 1993,34 1197. *lo P.H. EspecI B. Janssens and P.A. Jacobs J. Org. Chem. 1993,58 7688. *11 G. D. Yadav T. S. Thorat and P. S. Kumbhar Tetrahedron Lett. 1993,34 529. *I2 M. Davister and P. Laszlo Tetrahedron Latt. f993,34,533. *13 S. J. Barlow T.W. Bastock J.H. Clark and S.R. CulIen Tetrahedron Lett. 1993.34 3339. A. Cornelis P.Lado and S. Wang Tetruhedron Lett. 1993,34 3849. 'Is Y. V. Subba Rao S. J. Kulkami M. Subrahmanyam and A. V. Rama Rao Tetrahedron Lett. 1993,34 7799. H. Sbarghi and H. Eshghi Bull. Chem. SOC.Jpn. 1993,66 135. G. Lai and W. K.Anderson Tetruhedron Lett. 1993,34 6849. L.G. Beholz and J. R. StiIIe J. Org. Chem. 1993 58 5095. A.P. Churlton (Scheme 131.' l9 Unconventional regiospecific synthesis of aromatic carboxamides (58) by means of tin-mediated Friedel-Crafts reactions has been achieved (Scheme 13).' *O Thismethodologycan also be used for the preparation ofsulfonamides. Friedel-Crafts acylation and alkylation have been shown to take place in a single stage in the presence of aprotic superacids (Scheme 13).12' -Q R' Reagents i Ga,C1,;'2* ii A1C1,;1210-20"C122 Scheme 13 Conjugated dienones add to electron-rich arenes in a Friedel-Crafts annulation process that creates tricyclic compounds containing a central seven-rnembered ring (Scheme 14).'22 This method has been used as the key step in the synthesis of the diterpene baxbatusol (59).lZ3 A number of interesting Lewis acid mediated electrophihc substitution reactions related to the Friedel-Crafts reaction have been reported (Scheme 15).124-128 Direct aromatic amination has an advantage over the traditional method of reduction of the corresponding nitro compound- A number of novel direct amination methods have been developed.Azides in the presence of trifluoromethane sulfonic acid give the amino diazoniurn cation (RNHN,)' which reacts with arenes to give aromatic amides. 29. 30 Electron-rich arenes are regioselectively aminatedunder mild neutral conditions (Scheme 16).13' 'I9 Y. Hashimoto K. Hirata B.Kagoshima N. Kihara M.Hasegawa and K.Saigo Tetrahedron 1993,49 5969. M.Amswald and W.P. Neumann .I.Org. Chem. 1993,58,7022. 12' I. Akhrem A. OrIinkav and M.Volpin J. Chem. Soc. Chem. Commun. 1993,257. 12' G.Majctich Y. Zhang T. L. Feltman and V. Belfourt Tetrahedron Lett. 1993 34,441. 123 G. Majetich Y. Zhang. T. L. Feltman. and S.Duncan,Jr Tetrahedron Leu. 1993 34,445. J.N. Kim and E. K. Ryu Tetrahedron Lett. 1993,34 3567. 125 A. P.Yakubov D. V. Tsyganov L.I. klenlkii and M. M. Krayushkin Tetrahedron 1993,49 3397. 126 A.R. Katritsky L. Xie A. S. Afridi W.-Q. Fan and W. Kumictkicwicz Synthesis 1993 47. 12' A. W. van der Made and R. H. van der Made J. Org. Chem. 1993 58 1263. ''' G.A. OIah Q. Wang X.-Y.Li and S. Prakash SYNLETT 1993 32. H. Takeuchi T.Adachi H.Nishiguchi K.Itou and K. Koyama J. Chem.Soc. Perkin Trans.I 1993,867. G.A. Olah P. Ramaiah Q. Wang and G.K.S. Prakash J. Org. Chem. 1993 58 6901. 13' I.Zaltsgcndler Y. kblanc and M. A. Bernstein Tetrahedron Lett. 1993 34 2441. 12' Aromatic Compounds Reagents BF,-Et,O (59) Scheme 14 R iii t d VBt R Reagents i EtS 1-CF,CH(O lzt BF,; ii CJ (Cl)(SAr)R BF,; iii (CH,O), HBr IOAc; iv MeOCI AICI,; v ArCN'-O- AICI Scheme 15 P;IH* X = OMe OBn NMe2 Reagents i LICIO,; ii Zn/HOAc Scheme 16 Oxygen can also be introduced directIy into aromatic systems with the use of HOF-CH,CN complex or CH,0F.1.32Tritium can be introduced into activated aromatic compounds using BF,-Et,O and tritiated water. 133 An unorthodox rate enhancement in the Mannich reaction has been observed. M. Kol and S. Rozens J. Org. Chem. 1993 58,1593. P. McGeady and R. Croteau J. Chem.SOC.,Chem. Commun.1993,775. 5,,2an 162 A. P. Chorlton Under classical conditions the Mannich reaction is dramatically slowed after the formation of the mono-substituted product. Leigh has found that introduction of an electron-withdrawing group into the paw-position of phenol facilitates the formation of the disubstituted product in high yields.134 The heating rates associated with microwave heating have been used to control the isomeric ratio in suIfonation of na~htha1ene.l~~ Cerfontain has carried out an in-depth study into the sulfonation of naphthalene containing oxy substituents. 36-13' The thermal decomposition of meta-ditoluidinium sulfate to give ortho-rnethylsulfonic acid has been monitored. The rate-determining step for this reaction appears to be proton transfer to give an absorbed phase of meta-toluidine and sulfuric acid prior to sulfonation.'39 Nucleophilic Substitution.-Aromatic nucleophilic substitution has been the subject of debate by a number of workers. The major issue of interest concerns nucleophilic substitution reactions that occur through a chain process with radicals and radical anions as intermediates. The propagation reactions proposed have been among others the dissociation of the radical anion intermediate of the substrate to give a radical which reacts with the nucleophile (SRNlmechanism) or the reaction of such a radical anion with a nucleophile to give the substitution product (SRN2mechanism). Denney has questioned the validity of the SR,l mechanism because these reactions are known to take place with radical anions that are stable to dissociation thus favouring These claims have been rebuffed by Rossi who favours an S,,1 mechanism based on kinetic gro~nds.'~' Others have also put forward evidence for S,,l mechanisms.142-144 Alternative mechanisms are also possible for aromatic nucleophilic substitution.Zhang has proposed an S,Ztype non-chain radical process in the reaction of p-nitrochlorobenzene with the sodium salt of ethyl ar-cy-an~acetate.'~'**~~ In a study of the hydrolysis of ethers of 2,4-dinitrophenoIs de Rossi has found no evidence for a single-electron transfer mechanism thus pointing to the classical two-electron addition4imination reaction. 14' The mechanism of aromatic nucleophilic substitution where amines are the nucleophiles has been intensively investigated.14' -154 Aromatic nucleophilic substitution with carbon nucleophiles is an important 134 D.A.Leigh P. Linnane and G. Jackson Tetrahedron Lett. 1993,34 5639. 13' D. Stuerga K. Gonon and M. Lallemant Tetrahedron 1993 49 6229. 136 H.R.W. Ansink E. Zelvelder and H. Cerfontain Red. Trao. Chim. Pays-Bas 1993 112 2fO. 137 H. R.W. Ansink E. Zclvelder and H. Cerfontain Red. Trao. Ckim. Puys-Bas 1993 112 216. 13' Ii.R. W. Ansink E. Zelvelder and H. Cerfontain J. Chem. Soc. Perkin Trans. 2 1993 721. G. Singh I.P.S. Kapoor and M. Jain J. Chem. Soc. Perkin Trans. 2 1993 1521. I** B. Denney D.Z. Denney and A. J. Perez Tetrahedron 1993,49 4453. ''* R.A. Rossi and S.M. Palacios Tetrahedron 1993 49,4485.E.C. Ashby R. Gurunmurthy and R.W. Ridlehuber J. Org. Chem. f993 58 5832. S. Montanari C. Paradisi and G. Scorrano J. Org. Chem. 1993 58 5628. I** C. Galli and P. Gentili J. Chem. Soc. Perkin Truns. 2 1993 1135. X.M. Zhang D.-L. Yang and X.Q.-Jia and Y.-C. Liu J. Org-Chem. 1993,58 7350. X.-M. Zhang D.-L. Yang and Y.-C. Liu J. Org. Chem. 1993 58,224. i47 E.B.de Vargas E. L. Setti M. L. Aimar and R.H.de Rossi J. Org. Chem. 1993 58 7354. N. S. Nadelman M. Marder and A. Gurevich J. Chem. SOC.,Perkin Truns. 2 1993 229. *49 R.Chamberlin and M.R. Crampton J. Chem. Res. (S) 1993 106. "O R. Chamberlin and M. R. Crampton J. Chem. Soc. Perkin Truns. 2 1993 75. "' E.T. Akinyele D.-F. Crist and J. Hirst J. Ckem. Soc. Perkin Trans. 2 1993 905. '" S.Sekiguchi M. Hosokawa T.Suzuki and M. Sato J. Chem. SOC. Perkin Trans. 2 1993 1111. lS3 T.A. Emokpae P.U.Uwakwe and J. Hirst J. Chem. Soc. Perkin Trans. 2 1993 125. 15* T. Ibata X. Zou,and T. Demura Tetrahedron Lett. 1993 34,5613. Aromatic Compounds method for the formation of carbon-rbon bonds; a number of examples are given in Scheme 17.'55-160 0 Q / Reagents i H,C=CR(ONa); ii (A); iii ArMgBr; iv (B); v. Na(H,C=CO,Bu') FeSO Scbeme 17 Miyano has demonstrated that Grignard reagents can displace methoxy groups.156*i 57 The scope of this reaction has been extended by the utilization of sodium alkoxides and lithium amides as nucleophiles to give alkoxybenzenes and aromatic amines respective€y.'61.'62 Non-activated aromatic bromides are subject to methoxylation under mild and selective conditions when copper associated with carbon dioxide is used as a catalyst with sodium methoxide.163 2,4-Dinitrochloroben-zene undergoes halogen-exchange fluorination with hydrogen fluoride-base solutions to afford the corresponding fluorides.'64 Aryl phosphines can be readily synthesized from aryl fluorides by nucleophilic substitution with potassium diphenylphosphine. ti5 Regioselective control can be achieved in aromatic nucleophilic substitution of 2?4-difIuorocarbony1 aryls. The carbonyl group of an aldehyde or ketone directs Is' C Dell'Erba M. Novi G. PctriDo and C. Tavani Tetrahedron latt. 1993 34 235. T.Hattori H. Hotta T. Suzuki and S. Miyano Bull. Chem. Soc. Jpn.* 1993,44 613. "'T. Hattori T.Suzuki N.Hayashizaka N. Koike,and S,Miyamo 5uU. Ckem. SOC.Jpn. 1993,6&,3034. W.-Y.Zhao and 2.-T. Huang Syntk Commun. 1993 23,2533. 159 H.Medebielle M. A. Oturan J. Pinson and J.-M. Saveant Tetrahedron LRtt. 1993,34 3409. 16* M. van Leeuwen and A. McKiIlop 3. Chem. SOC.,Perkin Trans. 1 1993,2433. T. Hattori S. Satoh and S. Miyano Bull. Chem. Soc. Jpn. 1993 66 3840. W.ten Hoeve C. G. Krusc J. N. Luteyn J. R. G.Thiecke and €3. Wynkrg J. Org. Chem. 1993,58,5101. 163 D. NobcI J. Chem. Soc. Chem. Commun. 1993,419. 16* T. Fukuhara and N. Yoncda Chem. Lett. 1993 509. S.J. Coote G.J. Dawson C. G. Frost and J. M. J. WiIliams SYNLETT 1993 509. A. P. Chorlton nudeophiIic displacement to the ortho-position in preference to the para-position.s66 The application of vicarious nucleophilic substitution (VNS) of hydrogen allows the direct isocyanornethylation of nitroarenes (Scheme 18).'67 Reagents i Bu'OK DMF; ii CO, AcOEt Scheme 18 A VNS process is thought to be responsible for the facile rnonobromination of 174-benzodithians (Scheme 19).16* Y &-' Br H Br I &I] 9-b;)7a) 1 Br2 HBr Br Br-I Br Br-Scheme 19 An unprecedented intramolecular nucleophilic addition process rather than that of substitution of a diazonium salt has been reported (Scheme 20).169 Reagents i HNO,; ii NifCN) Scheme 20 166 D.M. Fink and J.T. Stupczewski Tetrahedron Len. 1993 34 6525. M. Makosza A. Kimowski and S. Ostrowski Synthesis 1993 1215. R. Caputo M. DeNisco and G. Palumbo Tetrahedron 1993 49 11383.C.A. Panetta Z. Fang and N. E. Heirner J. Org. Chern. 1993 58 6146. Aromafic Compounds 155 A new carboannulation strategy has been developed that involves an intramolecular nucleophilic addition ofsilyl enol ethers to photosensitized electron-transfer generated arene radical cations (Scheme 21).170 Reagents i hv CH,CN H,O; ii 1,4-dicyanonaphthalene Scheme 21 Substitution via Organornetallic Intermediates. The regiospecific nature of directed ortho-metallation (DoM) over cIassica1 electrophilic aromatic substitution methods continues to be exploited in the synthesis of aromatic compounds. Amides and ethers are still the most common DoM groups to be used fur this purpose. The asymmetric synthesis of optically active phthalides via DoM and the efficient conversion of alkylphenols into salicyclic acids are examples of their use (Scheme 22).17 72 0 iii.. Reagents i BuLi; ii RCHO; iii CO,; iv HOAc Scheme 22 A number of other DoM groups have been effectively utilized; these include aromatic aldimines (which act as ortho-lithiated protected aldehydes) and the thiolate group.173.174 The silanoIate group has been evaluated as a DoM group but it suffers from nucleophilic attack thus reducing its synthetic potential.' 75 The regioselectivity of DoM can be effected by manipulation of the side chain adjacent to the amide functionality (Scheme Changing the base used for metallation from an organolithiurn to a superbase also effects the regioselectivity (Scheme 23). 77 170 G.Pandey A. Krishna K. Girija and M. Karthikeyan Tetrahedron Lett. 1993 34 6631. 17' S. Matsui A. Uejirna Y. Suziki and K. Tanaka J. Chem. SOC. Perkin Trans. 1 1993 701. 172 A. R. Katritzky H. Lang and X. Lan Synth. Commun.,1993 23 1175. 173 L. A. Flippin J. M. Muchowski,and D. S. Carter J. Org. Chem. 1993 58 2462. 11A S. Masson J.-F. Saint-Clair and M. Saquat Synthesis 1993 485. S. McN. Sieburth and L. Fensterbank J. Org. Chem. 1993,58 6314. G. Katsoulos and M.Schlosser Tetrahedron Lett. 1993 34 6263. S. Cabiddu C. Fattuoni C. FLoris G. Gelli and S. Melis Tetrahedron,1993 49 4965. A. P. Chorlton OMe Reagents i BuLi; ii E’; iii BuLi BuOK Scheme 23 The efficiencies of DoM for a series consisting of secondary benzamides tertiary bemamines and benzylic alcohols have been reported.It was found for both amidic series that the efficiencies increase as the oxygen and the ortho hydrogen in the substrate are more coplanar with the aromatic ring. However for the alcohol series the opposite order is observed; this is thought to be due to shielding caused by association of the aIkoxide with two lithiurns as opposed to one in the amidic case.17* Palladium-catalysed cross-coupling reactions continue to be widely used for functionalization of aromatic compounds. The utility of the Heck reaction arylation of olefins has been extended to the arylation of vinylamine~”~and to reactions in aqueous media.’ The mode of reaction of the palladium-catalysed reaction of vinyl borate (60)and aryl halides can be varied to favour Heck or Suzuki-type processes by careful control of the reaction conditions (Scheme 24).Ia1 (a) Heck.(b) Suzuki. Reagents ArX Pd(o) scheme 24 The palladium-catalysed coupling between organostannanes and unsaturated P.Beak,S.T. Kerrick and D. J. Gallagher J. Am. Chem. Soc. 1993 115 10268. lt9 C. A. Busacca R.E. Johnson,and J. Swestock .I.Urg. Chem. 1993,58 3299. S. Sengupta and S. Bhattacharga J. Chem. Soc. Perkin Trans. 1 1993 1943. A. R. Hunt S.K.Stewart and A. Whiting. TetrahedronLett. 1993 34,3599. Aromatic Compounds 167 halides or sulfonates the Stille reaction has been the subject of a comprehensive study.182 Aryl alkynes can be synthesized by the palladium-catalysed reaction of aryl triflates with terminal alkynes.183 The synthetic transformations ofaryl triflates has been revie~ed.''~ The biaryl nucleus is present in a number of natural products and is a key feature in chiral catalysts (e.g.BINAP) and in bidentate ligands. This has resulted in new developments in the methodology for their formation. Lipshutz has synthesized biaryls uiu higher order cyano cuprates. (Scheme 25).' 85 Meyers has used oxazohe-mediated biaryl coupling and the Ullman reaction to prepare multifunctional chiral biaryls. 88 The cross-coupling of arytzinc com-pounds with aryl halides has been exploited to prepare unsymmetrical biaryls. 189*190 The mechanism of the Ullman coupling reaction on absorbed monolayers has been studied."' Barrett has developed a catalytic procedure for the oxidative coupling of phenols (Scheme 26).'" &h2+&)ltpFs72 g \ +J$J$ L Me Me (A) Reagents 10mol % (C) Cs,CO, PhBr scheme 26 Organolithium compounds are often formed by bromine-lithium exchange between the appropriate brominated precursors.The use of the more readily available chloroaromatics should be avoided due to their €ower reactivity. This process can be made viable by the addition of a naphthalene ~ata1yst.l~~ The reaction of ortho-V. Farina B.Krishnan D. R.Marshall and G. P. Roth 1.Org. Chem. 1993,58 5434. M. Alarni F. Fern and G. LinstrurneIle Tetrahedron LRtt. 1993 34,6403. K. Ritter SYNLETT 1993,735. B. H. Lipshutz K. Siegmann E.Garcia and F. Kayser J. Am. Chem. Soc. 1993 115,9275. M.Moorlag and A. I. Meyers Tetrahedron Lett.1993,34,6989. H. Moorlag and A.I. Meyers Tetrukdrun Lett. 1993 34 6993. la' T. P.Nelson and A.I. Meyers Tetrahedron Lett. 1993 34 3051. K. Takagi Chem. Lett. 1993,469. S. SibiIle V. Ratovelomanana J.V. NedeIec and J. Perichon SYNLETT 1933,425. 19' M. Xi and 3.F. Bent J. Am. Chem. Sm.,1993 115.7426. 192 A.G.M.Barrett T. Itoh and E. M. Wallace Tetrahedron Latt. 1993 34,2233. 193 A.G. Gudarro D.J. Ramon and M. Yus Tetrahedron Lett. 1993 34,469. 19' 168 A. P. Chorlton haloiodobenzenes with activated copper gives at ambient temperature a stable on ortho-halophenylcoppr reagent. 194 The use of arene chromium tricarbonyl complexes in organic synthesis has been re~iewed.'~',~~~ Substitution via Aryl Radicak The production of aryl radicals from para-methoxyben-zenediazonium tetrafluoroborate is accelerated in the presence of catechol and its derivatives.EPR and spin-trapping investigations indicate that this rednctiun process is catalysed by semiquinone radical^.'^' Aryl radicals are also formed by the reduction of aryltrirnethylammonium cations. Examination of this process demonstrates that the trimethyIammonium group can be expelled in much the same manner as chlorine atoms thus promising application in organic synthesis.fg8 Triphenylsulfonium salts undergo photochemical or electrochemical decomposition to generate aryl radicals. 99 Cyanobenzenes have been shown to undergo photochemical substitution with olefins allylic organornetallics and alkyl silanes (Scheme 27).200-202 CUZR I $R + CN I 6+ CN YR1 =LR3-NC NC Reagents i hv CH,CN; ii hv RSiMe,Y Scheme 27 A number of new photochemical methods have been developed that allow the introductionof fluorinated alkyls into the aryl nucleus.Mallouk has demonstrated that silver triflate can be used as a source of trifluoromethyl radicals which subsequently 194 G. W. Ebert D. R. Pfenning S. D. Suchen and T.A. Donovan Jr. Tetrahedron Lett. 1993 34,2279. 19' S.G. Davies and T.J. Donohoe SYNLETT 1993 323. 19' M. Sodeoka and M. Shibasaki SYNLETT 1993 643. 197 K. J. Reszka and C.F. Chignell 1.Am. Chem. SOC. 1993 115 7752. 19' V. V. Konovalov I. I. Bilkis B. A. Selivanov V. D. Shteingarts,and V. D. Tsvetkov J. Chem.Soc. Perkin Trans. 2 1993 1707.199 A. Stasko P.Rapta V. Brezova 0.Nuyken and R. Vogel Tetrahedron i993 49 10917. K. McMahon and D. R. Arnold Can. J. Cbem. 1992 71,450. '** K. Nakanshi K. Mizuno and V. Otsuji Bull. Chem. SOC.Jpn. f993,66 2371. 202 M. MelIa N. d'Alessandro M. Freccero and A. Albini J. Chem. Soc. Perkin Trans. 2 1993 515. Aromatic Compounds can substitute C-h~drogen.~'~ Perfluoroalkylation of anilines has been reported; this process involves initial charge-transfer complex formation between the aniIine and perfluoroalkyl iodides. The complex then undergoes photo-induced electron transfer to give a radical cation intermediate which attacks the ar~iline."~ Penta- fluorophenylation of arenes can be effected via photochemical-induced reaction of pentafluorophenylalkane sulfonates with a wide variety of aromatic compounds.205 Di- and trihalobenzenes undergo ips0 substitution on reaction with benzyl radicals to give halo- and dihalodiphenylmethanes respectively.206 Intramolecular radical ips0 substitution is thought to be responsible for the conversion ofarylpropyl bromides (611 into arylpropanols (62)(Scheme 28).207 (611 Reagents [CH,(CH ,SnH Scheme 28 The oxidation of benzene to phenol with Underfriend's reagent (Fe2+-EDTA + 0 + L-absorbic acid) has been examined and evidence is presented fur hydroxyl radicals as the activated species.203 5 Condensed Polycyclic Aromatic Compounds Benzenoid Aromatics.-The discovery that buckminsterfullerene CeO,is a stable molecule due to geodesic and electronic properties has generated a renewed interest in hydrocarbons that resemble a portion of the C, surface.The carbon framework of corannulene (53)can be considered to represent the poIar cap of C60.In spite of its curvature corannulene undergoes rapid bowl-to-bowl inversion. Incorporation of the corannulene structure into C6,, would require the bowl to be in a locked conformation. Rabideau has demonstrated that the bowl becomes rigid with only the addition of two carbons thus giving the fused five membered ring derivative The corannuhe tetraanion has also been subject of debate. The possibility of the. tetraanion being viewed as a cyclopentadienyl anion inner core with the remaining three electrons at the periphery of the molecule producing an 18-x-electron trianion has been raised.Calculationsdo not lend much support to this hypothesis and attempted formation of lo the tetraanion and protonation have also The bowl shaped hydrocarbon sumanene (55)can also be regarded as a precursor to the synthesis of C60. The synthesis of sumanene has not been reported; Mehta has reported his achievements towards this target but unfortunateIy this route fails at the '03 C. Lai and T. E. Malbuk J. Chem. SOC.,Chem. Commun. 1993 1359. Q.-Y. Chem Z.-T. Li and C.-M. Zhou J. Chem. Soc. Perkin Trans. 1 1993 2457. '05 Q.-Y. Chen and Z.T. Li J. Org. Chem. 1993 58 2599. '06 R. Henriquez and D.C. Nonhebel Tetrahedron I993,49,5497. '07 E. Lee C. Lee J.S. Tae H.S. Whang and K. S. Li Tetrnhedron Lett. 1993 34 2343. '08 S. Ito K.Ueno A. Mitarai and K. Sasaki J. Chem. SOC., Perkin Trans. 2 1993 255. '09 A. H. Abdourazak A. Sygula and P. W. Rabideau J. Am. Chern. SOC. 1993 115 3010. 'lo P.W. Rabideau Z. Marcinow R. Sygyula and A. Sygyla Tetrahedron Lett. 1993 34 5351. 170 A. P. Chorlton Reagents FVP 850 "C lo-* Torr Scheme 29 last step" (Scheme 29). Plater has suggested the synthesis of C, from suitable polycyclic aromatic hydrocarbon (PAH) precursors. A number of appropriate PAHs have been syn-thesized towards this aim the most complex king 1,3,5-tri(benzol[c]phenanthren-9-y1)benzene (66),which could be envisaged under suitable gas-phase dehydrogenation conditions to close up like the petals of a Bower to yield C,,.2'* (66) Cydopentene-fused PAHs are related to C, in that they are constructed of fused hexagonai and pentagonal arrays of carbon atoms.The reactivity of these nonalternate 'I' G. Mehta S. R. Shtah and K. Ravikurnar J. Chem. Soc. Chem. Commun. 1993,1007. M.J. Plater SYNLETT. 1993 405. Aromatic Compounds PAHs is frequently different from alternate PAHs. A detailed study of the electronic behaviour of a series of nonalternate PAHs has been accompIished using heavy atom perturbation effects.213 Methylene bridged PAHs are ubiquitous environmental pollutants often formed by incomplete combustion of fossil fuels. These PAHs have been shown to exhibit potent tumourigenic activity. However surprisingly little is known concerning their chemistry or biological properties. This situation has been remedied by the synthesis of these compounds by standard te~hniques.~’~-~l~ The electrophilic substitution and the catalytic reduction of a number of these PAHs has been studied.218-220 Th e carcinogenic properties of PAHs are thought to be due to oxidation of the bay region to give diol epoxides (67) which are implied as the ultimate carcinogenic metabolites.Evidence for this is the identification of its metabolic precursor trans-3,4-dihydrodiol (68). To permit biological study of these systems a number of workers have disclosed synthetic routes to these -224 Flash vacuum pyrolysis has proved to be useful in the synthesis of acenaphthylene and its derivatives (Scheme 30).225-227 The simple and rapid production of complex PAHs has been demonstrated; a number of the more interesting examples are highlighted in Scheme 31.2281230 Non-benzenoid Aromatics-l,6-Methano[ lO]annulene (69) a l0x-electron system can also exist in the less stable bisnorcaradiene form (70).Neidlein has demonstrated that bridging between the C-2and C-10 positions shifts the equilibrium in favour of the bisnorcaradiene structure (71).231 ’I3 B. F. Plummcr L. K.Steffen,T.L. Braley W. G. Recse K.Zych G.Van Dyke,and B. Tully J. Am.Chem. Soc. 1993 115 11542. 214 C. Yang and R.G.Harvey 3. Org. Chem. 1993.58,4155. 215 P. P. J. MuIdcr B. B. &re J. Comelisse and Lugtenburg Red. Trau. Chim. Pays-Bas 1993 112,255. 216 T. Gimisis J. W. Kampt and M. Koreeda J. Org. Chem. 1993,sS 5858. 217 M.J. Tanya and J. E. Bupp J. Org. Chem.1993,58,4173. B. P.Cho M. Kim,and R.G.Harvey J. Org. Chem. 19!43,58 5788. 219 M.Minabe R.Nishimura T. Kimura and M. Tsubota BuU. Chem. SOC.Jpn. 1993 66 1248. ”* M.Minabe S. Urushibara F. Mishina T. Kimura and M. Tsubota Bull. Chem.Soc. Jpn. 1993,66,670. ’” P. K.Sharma Synth. Cummun. 1993 23 389. 222 R.J. Young,C. Cortez E. Luna H. Lee and R.G.Harvey J. Org. Chem. 1993 58 356. 223 R. Agarwal and D. R. Boyde 3. Chem. Soc. Perkin Trans. 1 1993 2869. 224 Y.4. Wu J.-S.hi and P.P. Fu J. Org. Chem. 1993 58 7283. ’’’ R. F.C.Brown F. W. Eastwood and N. R. Wong Tetrahedron Lett. 1993 34 1223. 226 R.F.C. Brown,F. W. Eastwood and N. R. Wong Tetrahedron Lett. 1993 34 3607. U. E. Wiersum and L. W. Jeneskens Tetrahedron Lett. 1993 34 6615. G. Dyker J. Korning P.G.Jones and P.Bubenitschek Angew. Chem. Int. Ed. En& 1993,32 1733. 229 F.M. Raymo M. F. Pans and F. H. Kobnke Tetruhedron Lett. 1993 34 5331. 130 A. Ghanirni and J. Sirnonet Tetrahedron Lett. 1993 34 6893. 231 R. Neidlein and U. Kux Angew. Chem. Int. Ed. Engl. 1993,32 1324. A. P. Chorlton Scheme 30 Azulenes with systems that have a peripheral 14z-electron (72) and an 18n-eIectron (73)conjugation have been synthesi~ed.~~~.~~~ These systems show little contribution from the extra conjugation but rather are composed of two separate azulene-type n systems as in (73) and azuIene and fulvene systems as in (72). A series of methano-bridged-tetrahydro[2U-j- -[24]- -[25]- -[28]- -[30]- and -[32]annulenediones (74a)-(74f) have been synthesized.These compounds were expected to show the ring-current effect for the [4n + 21. or [4n]n-electron system arising from polarization of the two carbonyl groups. However contrary to these expectations the annulenediones showed weak tropicity presumably due to a low planarity of their molecular skeleton. The dication from the tetrahydrornethano[24]- annulendione (74b) is strongly diatropic due to possession of a 22n-electron aromatic system.234A similar dication of the methano[24]annulenedione (75) exhibits the strongest diatropicity recorded for a 22~-electron system.235 In an analogous study methanohomoC1 Slannulene (76) and methanohomo[ Wlannulene (77) were prepared. Protonation of these species should yieId the corresponding 1471 and Mz-electron 232 M.Yasunami J. Hoioki Y. Kitamori I. Kikuchs and K.Takase Bull. Chem. SOC.Jpn. 1993,66,2273. 233 M. Nitta K. Nishimura and Y. Ino Tetrahedron Lett. 1993 34 2157. 234 H. Higuchi K. Asano K. Nakafuku Y.Takai J. Ojima,andG. Yamamota,J. Chem.Suc. Perkin Trans. I 1993 89. ”’ G.Yamamoto H. Hignchi K. Asano and 1. Ojima Chem. Lett. 1993 1829. Aromatic Compounds jI OR OR OR OR Reagents:i 1,%-diiodonaphthalene;ii 1-iodonaphthaIene;iii mthracene xylene; iv HCIO, EtOH; v -&- -6H' Scheme 31 174 A. P. Chorlton OD OD (74a) [m]; m = n = 0 (74b)[24]; m = n = 1 (74c) pq m = 1; n = 2 (744 [28]; m = n = 2 (748) (3UJ; m = 2; n = 3 (740 1321;TI = n = 3 systems respectively. Attempts at the protonation of (76) and (77)were unsuccess- fu1.236 Hay coupling of the tetraethynylethene (78) gives the t12lannulene (79) and the [18]annulene (80); spectral examination of (79) and (80) confirms the expected antiaromatic character of the 12x-electron system and the aromatic character of the 18 n-electron It has been demonstrated that resonance stabilization in [25]annulene (81) is nut sufficient to stabilize the molecule in a planar conformation with aromatic properties.However if this 26~-electron perimeter incorporates four pyrrole units as in the L261porphyrin (82) then sufficient stabilization is present and the expected aromatic character is exhibited.' 38 6 Cyclophanes The strain and distortion imposed upon the benzene ring in cydophanes imparts an 236 H.Higuchi T. Hashimoto K. Nakafuku,J. Ojima and G.Yamamoto Bull. Chem.Soc. Jpn. 1993,66,294. 237 J. Anthony C. 3. Knobler and F. Diederich Angew. Chem. Znt. Ed. Engl. 1993,32,406. "* T. Wessel B. Franck M.Moller U. Rodewald and M. Lage,Angew. Chem. Int. Ed. Engl. 1993,32,1148. Aromatic Compounds R' x* R3 (78) Ff CuCl TMEDA I R RlR R + enhanced reactivity which can subsequently lead to unusual reactions. [6]Paracyc- lophanes undergo nucleophilic addition with Bu"Liand Bu'Li and formal nucleophilic substitution with Bu'Li. This is an example of nucleophilic substitution being effected under mild conditions considering that the benzene ring is not activated by strongly electron-withdrawing groups. This result is ascribed to the release in strain on the formation of the initial adduct (Scheme ?2).''' C2.2)Metacyclophanes undergo a novel Lewis-acid catatysed transannular cycliz- ation.The cyclization is attributable to the different Ir-electron densities of the two benzene rings which are separated from each other by two ethylene units (Scheme 33).240 Similar transannular cycIizations have been observed in the bromination of &substituted [2)metacyclo[2]( 1,3)pyrenophane~.~~' Transannular interactions in [2.2Jmetacyclophanes aIso affect the selectivity of the tricyanovinylation reaction with 239 Y.Tobe M.limbo S. Saiki K. Kakiuchi and K. Naemura J. Org. Chem. 1993.58 5883. 240 T. Yamato J.4. Matsumoto M. Shigekuni T. Ishili and M. Tashiro J. Chem. Res.(S) 1993,272.241 T. Yamato A. Miyazawa and M.Tashiro 1.Chem. Soc. Perkin Tram. I 1993 3127. A. P. Chorlton Reagents i RLi Scheme 32 Scheme 33 tetracyanoethylene (TCNE). In addition to the normal N-tricyanovinyl product 4-arnino[2.2]metacyclophane reacts with TCNE to give oxaziridine derivatives (Scheme 34).242 Scheme 34 The highly strained Adamantanophane (83)renders the benzene ring susceptible to dienophile addition in a Diels-Alder reaction.243 Similar Diels-Alder reactions with the mono-(Dewar benzene) isomer of [l .l]metacyclophane have also been observed (Scheme 35).244 The intramolecular interaction between the aromatic rings of small cyclophanes has been the subject of a number of investigations. 8,16-Dimethoxy[2.2]metacyclophane (84) undergoes the diazo coupling reaction easily in one ring but never in both.The absorption maxima of a series of azo compounds was found to be bathochromically shifted from those of model reference compounds. When the A,, values of the azo compound that carries a functional group in the couter (C-13) position are plotted 14' A.A. Aly A. A. Hassan and A.-F.E. Mourad Can. .I.Chem. 1993,71 1845. 2A3 R. Lernmen M. Nieger and F.Vogtle J. Chem. SOL Chem. Comun. 1993,1158. "* G.W. Wijsman D. S. Van Es W. B.de Wolf and F. Bickelhaupt Angew. Chem. Inr. Ed. Engl. 1993,32 726. Aromatic Compounds Reagents MeO,CCECCO,Me; ii 0 Scheme 35 against the substituent Hammett constants (a,p) a straight line is obtained. These results establish that the electronic effects of the functionaI group are transmitted between the two aromatic rings in [2.2]metacyclophanes by a through-space interaction (Scheme 36).245 (W Reagents PhNl Scheme 36 Through-space interactions have also been observed in the stabilization of the naphthyl- 1-tropylium ion by [2.2]paracycIophane fixed at the position (C-8-C-5') face-to-face to the tropylium ring (85).246 The electronic properties of benzoannelated C22lparacyclophane (86) have been studied; such rnoIecuIes are found to be highly efficientelectron acceptors.The unusual geometry of the carbon framework alIows reversibk acceptance of four to six electrons thus making it an attractive model for a charge-storage system.247 The last and most 245 A. Tsuge,T. Moriguchi S.Mataka and M.Tachiro J. Chem. Soc. Perkin Trans. I 1993,2211. ''' K. Kornatsu R. Tsuji Y. Inouc and K. Takeuchi Tetrahedron Lett. 1993,34,99. '" 0.Reiser B. Konig K. Meerholz J. Heinze T. Wtllauer F. Gerson R.Frim M. Ravinovitz and A. de Meijere J. Am. Chern. Soc. 1993 115 3511. A. P. Chorlton strained [2.2]cyclophane (87) has been synthesized; the thermal isomerization of the Dewar benzene valence isomer (88) is the key step.248 248 Y.Tobe M.Kawaguchi K.KakiuLhi and K.Naemura J. Am. Chem. Soc.,1993,115 1173.