4 Reaction Mechanisms Part (i)Pericyclic Reactions By G. B. GILL Department of Chemistry University of Nottingham Nottingham NG7 2RD 1 Introduction Pericyclic reactions continue to be an extremely popular and profitable area of study. Major preoccupations of much of this work have been the synthesis of natural products or exploration of synthesis methodology as in the study of tandem sigmatropic rearrangements. Details of such applications are to be found elsewhere in Annual Reports. Ene and Diels-Alder reactions of singlet oxygen with olefins and 1,3-dienes have been reviewed.' The zwitterionic peroxide mechanism is the model whereby the regioselectivity of the hydroperoxidation of tetra-substituted olefins by '02can be rationalized.2 However ab initio MO (4-3 1G) calculations on the '02-propene reaction affords results that are interpreted as a preference for a concerted mechan- ism involving a transition state such as (l).3Both ab initio and semi-empirical calculations predict that perepoxides are too high in energy to qualify as reaction intermediates as are zwitterions for weakly polar alkenes.Although 1,4-diradical intermediates are calculated to be more stable reactions of such species should be non-stereospecific yet should show significant regioselectivities contrary to experi- mental observations for the '02-olefin reactions Hence these calculations appear to exclude all but the concerted mechani~m.~ Evidence has been presented that reactivity and regioselectivity in these reactions may be the subject of conforma- tional control through differences in rotational barriers.' The desirable perpen- dicular conformation (2) with <1234 = 90" is intermediate in energy between the more stable eclipsed conformation (3) <1234 = O" and the more energetic staggered conformation (4) <1234 = 180".Experimental and calculated rotational barriers for Me groups substituting propene are increased by gem-Me substitution (Me2C=CH2) unchanged by trans-Me substitution [(E)-MeCH=CHMe] and decreased for cis-Me substitution [(Z)-MeCH=CHMe].For 2-methylbut-2-ene (5) the percentage H abstraction and rotational barriers (in parentheses kcal ' H. H. Wasserman and J. L. Ives Tetrahedron 1981,37 1825;A.A. Gorman and M. A. J. Rodgers Chem. SUC.Rev. 1981,10 205.C. W.Jefford Helv. Chim. Acta 1981,64 2534. K.Yaniaguchi T.Fueno I. Saito T. Matsuura and K. N. Houk Tetrahedron Lett. 1981,22 749. K.Yamaguchi S.Yabushita T. Fueno and K. N. Houk J. Am. Chem. Suc. 1981,103,5043. ' K. N. Houk J. C. Williams jun. P. A. Mitchell and K. Yamaguchi J. Am. Chem. Suc. 1981,103,949. 51 G. B. Gill 7-4 H--0 Q Me 53(0.47) MeAMe 40(0.61) 7(2.22) (5) mol-’) are as indicated. Thus the greater reactivity of alkyl groups on the disub- stituted side may arise from the relative ease of achieving the necessary perpen- dicular conformations; since all groups lower the rotational barrier of a cis-methyl this explanation of the ‘cis-eff ect’ is quite general. Chiral prosthetic groups have been employed as direct probes of the geometry of the transition state of the Diels-Alder reaction and co-operativity in asymmetric induction is demonstrated to be a direct result of the concertedness of the reactiom6 The relative rate of enantiomer formation (k,/k,) in the presence of two chiral groups will be the product of the rates in the presence of one chiral group that is the linear free-energy corre,lation has the form k,/kp = kalka2/kBlkD2.This relationship is demonstrated by the measured product ratios for the quantitative cycloaddition of 1,3-diphenylisobenzofuranto dialkyl fumarates (6) to give the adducts (7) (R’,R2 = Me,Me Me,l-bornyl or I-borny1,l-bornyl). (6) (7) Ab initio SCF-MO calculations utilizing a STO-3G basis set have been applied for example to 7-hydroxynorbornadiene in which it is demonstrated that the olefinic C-H bonds are bent out of the C-1-C=C-C-4 plane in the endo direction (1.3” for the syn-H’s and 0.9” for the anti-H’~).’~From parallels of molecular distortions and .n-facial stereoselectivities the following general rule has been propo~ed:’~ ‘attack of a reagent at an unsaturated site occurs such as to minimize antibonding secondary orbital interactions between the critical frontier molecular orbital of the reagent and those of vicinal bonds’.Restricted Hartree- Fock calculations on the fragmentation of carbenadioxolane (8) indicate that the L. M. Tolbert and M. B. Ali J. Am. Chem. Soc. 1981,103,2104. (a)N. G. Rondan M. N. Paddon-Row P. Caramella and K. N. Houk J. Am. Chem.Soc. 1981,103 2436; (b) ibid. p. 2438. Reaction Mechanisms -Part (i) Pericyclic Reactions (8) diradical formed by cleavage of just one C-0 bond lies at least 8.8 kcal mol-' below the transition state for concerted fragmentation and it is concluded that the cleavage of one C-0 bond in (8) is a lower-energy process than concerted fragmentation.8 E (9) E = C02Me (10) Deuterium substitution confirms that cis-transfer of two endo-hydrogen atoms occurs in the thermal rearrangement of (9) at 130-160°C. The product (10) was isomerized to (9) when isolated and heated separately.' Thermochemical factors appear to rule out a free-radical mechanism and thus (9) + (10) is an example of the rarely observed concerted hydrogen-transfer rearrangement process k = (2.0 f 0.1) x lop6s-' at 130°C with AH' = 35-39 kcal mol-' and AS*= 2-1 1e.u.Dyotropic rearrangements are likewise comparatively uncommon. The lactones (11;X Y = 0)and lactols (11;X Y = H OH) underwent the indicated formal [2,2] dyotropic rearrangements upon thermolysis at 350 "C (n = 1or 2).1° 2 Cycloadditions and Cycloreversions A further review of intramolecular cycloaddition reactions as applied to the total synthesis of steroids has appeared." Although the stereoselectivities of the additions of acrylic acid derivatives (H,C=CHR; R = CHO C02Me or CN) to cyclopenta- diene in homogeneous solution are largely insensitive to changes in solvents and many catalysts the endo exo ratios are altered by the presence of a heterogeneous carrier substance.'* Thus for example the homogeneous thermal addition of acrolein (R = CHO) to cyclopentadiene affords a ca. 75 :25 mixture of endo exo D. Feller E. R. Davidson and W. T. Borden J. Am. Chem. Soc. 1981,103,2558. J.-P. Hagenbuch B. Stampfli and P. Vogel J. Am. Chem. SOC.,1981,103 3934. lo K. Satb Y. Yamashita and T. Mukai Tetrahedron Lett. 1981,22 5303. T. Kametani and H. Nemoto Tetrahedron 1981 37 3. '* H. Parlar and R. Baumann Angew. Chem. Znt. Ed. En& 1981,20 1014. G.B. Gill (4 + 2) adducts; in the presence of neutral alumina the ratio is altered to ca. 51 :49. In the related reaction of methyl acrylate (R=C02Me) the ratio for the homogeneous reaction ca. 75 :25 is altered to ca. 97 :3. In no case however was the endo preference overturned.Although (i) Lewis acid catalysis of Diels-Alder reactions is well documented (ii) the improvements in stereo- and regio-selectivities thus gained have found wide use in synthesis and (iii) the ca. lo6 rate accelerations have enabled many such processes to be conducted at relatively low temperatures the inherent need for specific complex formation between the Lewis acid and the dienophile does introduce a limitation the catalysed reactions being largely limited to those involving oxygen-bearing electron-deficient dienophiles. Alternative methods for providing rate enhancements are now available. The first of these utilizes the 'hydrophobic effect'; the results obtained for the rates of the (4 + 2) cycloaddition of N-ethyl maleimide to 9-hydroxymethylanthracene are i1lu~trative.l~ At 45 "C the rate con- stants (x lo5M-' s-') obtained for the reaction in various solvents were isoctane (796),butan-1-01 (666),methanol (344),acetonitrile (107),and water (22 600).The decrease in rate with increasing solvent polarity with a large increase for the heterogeneous aqueous system seems to implicate molecular aggregation due to the hydrophobic effect.With less bulky dienes/dienophiles the addition of p-cyclodextrin to provide a hydrophobic cavity provides an enhancement of rate over that of the water reaction; likewise the addition of lithium chloride to increase the hydrophobic effect also provided a rate enhancement (in this case however it is not clear from the data provided if the effect of LiCl may not at least in part be due to Lewis acid catalysis by Li+).In a quite different approach Diels-Alder re- actions have been accelerated by converting dienophiles into their corresponding cation radicals the particularly useful feature here being that neutral and electron- rich dienophiles are those that are most readily ionized to cation radi~a1s.l~ Thus treatment of cyclohexa-1,3-diene with tris(pbromopheny1)aminium hexachloro-stibnate [(~-Brc~&)~Nt SbC16-] in CH2C12 at 0 "C afforded in 15 min a 70% yield of the (4 + 2) adducts (endo:em = 5 :1); the thermal addition proceeds poorly (30%) giving a 4 1 product mixture in 20 h at 200°C. Similar reaction of cyclohexa-1,3-diene with 2,5-dimethylhexa-2,4-dienein the presence of the cation- radical salt gave the adducts (12; endo:exo = 4 :3).This result indicates a prefer- ence for the formation of the cation radical from the more alkylated diene and an unusually low sensitivity of the (4 + 2)t process to steric effects. A possible reaction mechanism is DP + Ar,Nt +Ar,N + DPt DPt + D +At At + DP +A + DP? (D = diene DP = dienophile and A = adduct). l3 D. C. Rideout and R. Breslow J. Am. Chem. Soc. 1980 102,7816. *' D. J. Bellville D. J. Wirth and N. L. Bauld J. Am. Chem. Soc. 1981 103 718. Reaction Mechanisms -Part (i) Pericyclic Reactions The reluctance of 1-azadienes to undergo cycloaddition reactions is emphasized by the work of two groups. l5 Reaction of the pentachloro-1 -azacyclopentadiene (13)with vinyl acetate gave only the (4 + 2) adduct resulting from the participation of the 2-azacyclopentadiene (14) a result ascribed to a less favourable enthalpy change for the 1-relative to the 2-azadiene Diels-Alder reactions.15a Whereas (13) functions as a dienophile in the addition to cyclopentadiene it reacts predominantly as a diene with cyclohexa-1,3-diene and with acyclic dienes such as trans-pipery- lene and then by way of the valence isomer (14).15’ As the HOMO energies of the hydrocarbon dienes are very similar the change in role of the azacyclopen- tadiene system from two- to four-electron cycloaddition component is thought to be determined largely by steric factors.The intramolecular (4 + 2) addition of N-acyl-1-aza- 1,3-dienes to olefinic double bonds has been successfully employed in the preparation of endocyclic enamines for example (15; n = 1 or 2).“ Asymmetric induction in Diels-Alder reactions has obvious synthetic applications and therefore continues to attract attention (see also ref.6). The observed asym- metric induction for (4 + 2) additions to (E)-buta-1,3-dienyl (S)-0-methylmande- late is a function of the dienophile and may be due to the importance of charge transfer intermediates in the r-stacking arrangement (16). The addition of juglone to this diene under B(OAc) catalysis proceeds with virtually quantitative enan- tioselectivity.” The results of (4 + 2) cycloadditions of anthracene to chiral dienophiles in which the functional groups are at ‘concave sites’ as in (17) have been compared with literature data for the corresponding menthyl methyl fumarates (functional groups at a ‘convex site’) stereoselectivities being appreciably greater for the former dienophiles (R = CH,Ph or CONPh) in both thermal and AlC1,- catalysed reactions.l8 The preferred topography for the transition states involves bonding with the diene on the side of the dienophile C=C in (17) remote from the methyl group at C-1. Chiral induction in the Diels-Alder addition of the menthyl acrylates (18; R = H or Ph) to cyclopentadiene has been found to depend upon the auxiliary chiral group and particularly the Lewis acid used to catalyse the reacti~n.’~ The adducts formed from the thermal (4 + 2) addition of unsymmetrical electron- rich dienes and methoxy benzoquinones or naphthoquinones are those in which the more nucleophilic diene terminus becomes bonded to the non-methoxylated l5 (a) M.E. Jung and J. J. Shapiro J. Am. Chem. Soc. 1980 102 7862; (b)B. Kh. Rammash C. M. Gladstone and J. L. Wong J. Org. Chem. 1981,46 3036. l6 Y.-S. Cheng F. W. Fowler and A. T. Lupo jun. J. Am. Chem. Soc. 1981,103,2090. l7 B. M. Trost D. O’Krongly and J. L. Belletire J. Am. Chem. Soc. 1980 102 7595. G. Helmchen and R. Schmierer Angew. Chem. Znt. Ed. Engl. 1981 20 205. l9 W. Oppolzer M. Kurth D. Reichlin and F. Moffatt Tetrahedron Lett. 1981 22 2545; see also W. Oppolzer M. Kurth D. Reichlin C. Chapuis M. Mohnhaupt and F. Moffatt Helu. Chim. Acru 1981 64 2802. G.B. Gill (16) (17) (18) carbon for example (19) + (20) +(21) through the minimization of repulsive steric eff ectsS2' Experimental results bear out the expected high dienophilic reac- tivities of the benzoquinone derivatives (22; X = 0or NPh).21 MNDO calculations indicate that C-2 and C-3 have the largest LUMO coefficients while the coefficients at C-1 and C-4 are larger than those at C-9 and C-11.The adducts are found to possess structures in accord with the predicted regioselectivity (addition to C-2 C-3) and stereoselectivity (endo with respect to the benzoquinone moiety). (19) (20) (21) @; 0 (22) A very unusual stereospecific addition of tetracyanoethylene to substituted cyclo- propanone thioacetals has been uncovered.22 Because of the observation of the formation of a coloured charge-transfer complex when the co-reactants are mixed it is suggested that TCNE approaches the cyclopropane ring in (23) at the face where the SMe group is situated.The two products formed from (23) and TCNE namely (24) and (25) could arise from the two alternative HOMO/LUMO combi- nations indicated that is by a formal [,2 + ,2,] cycloaddition. Among the very many examples of the application of cycloaddition reactions to synthesis that have been published this year a paper by Wender and Ho~bert~~ deserves specific mention since it breaks relatively new ground. It concerns the use of intramolecular 1,3-~hotoaddition of olefins to arenes in synthesis leading to the formation of three new rings and up to six new stereocentres. The paper provides an important analysis of the stereoelectronic features of these photo-cycloadditions 2o I.-M.Tegmo-Larsson M. D. Rozeboom and K. N. Houk Tetrahedron Lett. 1981 22 2043; I.-M. Tegmo-Larsson M. D. Rozeboom N. G. Rondan and K. N. Houk ibid. p. 2047; M. D. Rozeboom I.-M. Tegmo-Larsson and K. N. Houk J. Org. Chem. 1981,46 2338. 21 K. Kanematsu S. Morita S. Fukushima and E. dsawa J. Am. Chem. SOC., 1981,103,5211 ;S. Yoshino K. Hayakawa and K. Kanernatsu J. Org. Chem. 1981,46 3841. 22 P. G. Wiering J. W. Verhoeven and H. Steinberg J. Am. Chem. SOC.,1981 103 7675. 23 P. A. Wender and J. J. Howbert J. Am. Chem. SOC. 1981 103 688. Reaction Mechanisms -Part (i) Pericyclic Reactions NC CN NC CN Me CN CN OMe SMe bearing upon their potential use in synthesis and the validity of the arguments presented is demonstrated by an elegant four-step synthesis of (*)-a-cedrene from a simple benzoid precursor.3 Ene Reactions Regio- and stereo-selective syntheses of cyclic natural products by intramolecular cycloadditions and ene reactions have been reviewed.24 The stereoselective introduction of steroid side chains at C-17 and C-20 has been achieved by two groups with the aid of Lewis acid-catalysed intermolecular ene additions to the A17‘*O’ ster~id.~~**~ Thus for example the Et,AlCl-catalysed addition of methyl propiolate to the (17Z)-ethylidene steroid proceeds as expected by a-attack as shown in (26) and sets the stereochemistry of the C-20 carbon in the natural onf figuration.^^ Other enophiles can be added similarly and reaction at a prochiral unsaturated centre in the enophile proceeds with good stereoselectivity.26 The transfer of axial chirality into kentral chirality is observed in the thermal intramolecular ene reaction of the optically active y-allenic aldehyde (27) by way of the endo transition-state geometry indi~ated.~’ 24 W.Oppolzer Pure Appl. Chem. 1981 53 1181. 25 W. G. Dauben and T. Brookhart J. Am. Chem. SOC.,1981,103,237. 26 A. D. Batcho D. E. Berger S. G. Davoust P. M. Wovkulich and M. R. UskokoviC Helv. Chim. Acta 1981,64 1682. 27 M. Bertrand M. L. Roumestant and P. Sylvestre-Panthet Tetrahedron Lett. 1981 22 3589. G.B. Gill R R I R I ~I (28) R = Me OAlR,,Cl,-, (291 2 equiv. Me,AICI "x"' OAl R,,Cl,-, OAlR .C12 -,, (31) b=/d (30) (32) The use of alkylaluminium halides as Lewis acids (with Brgnsted base reactivity) for promoting ene reactions has been further explored by Snider's group.28a The precise choice of alkylaluminium halide its quantity and the reaction temperature can have an important bearing upon the reaction pathway.Thus for example treatment of 2,6-dimethyl-5-heptenal (28) with 1equivalent of Me2AlC1 at -80 "C affords the ene adduct (29) presumably by the concerted mechanism indicated.28b With 2 equivalents of Lewis acid the more electrophilic aldehyde-(Me2A1C1)2 complex can form and the production of the chloro-alcohol (31) implicates the intermediacy of the carbonium ion (30). Use of the more acidic Lewis acid MeAlCl at -80 "C on the other hand afforded mainly (32) which is probably formed from (30) by way of two 1,2-hydride shifts.The methyl a-cyanoacrylate-Me,AlCl com-plex reacts with alkenes to give ene adducts dihydropyrans and cyclobutanes by way of the initially formed zwitterion (33); 2 1adducts are formed by the intercep- tion of (33) with another molecule of methyl a-cyanoacrylate.28C The proton- scavenging action of the alkylaluminium halides is frequently crucial. It allows for example observation of the ene-type addition of aryl sulphinyl chlorides to alkenes (Et ,AlC1 catalysis). 28d Kinetic hydrogen-isotope effects have been studied in order to determine any differences in mechanism between thermal and SnC1,-catalysed ene reactions of oxomalonic esters (34; E = C02Me or C02Et).29 Primary isotope effects are high (kH/kD = 3.3) in the thermal reactions (130°C) and negligible (kH/kD = 1.1)in the catalysed cases (25 "C) even where intramolecular H/D competitions are available.Concerted mechanisms with variations in C-C bond formation and C-H(D) bond breaking are proposed. The pressure dependence (1-1325 bars) of the rate constant (1.39 -5.75 x 1 m-'s-') for the ene addition of dimethyl oxomalonate (34; E = C0,Me) to hex-1-ene reveals that AV' = -28 to 28 (a)B. B. Snider D. J. Rodini M. Karras T. C. Kirk E. A. Deutsch R. Cordova and R. T. Price Tetrahedron 1981 37 3927; (b) M. Karras and B. B. Snider J. Am. Chem. SOC.,1980 102 7953; (c) B. B. Snider and G. B. Phillips J. Org. Chem. '-981 46 2563; (d) B. B. Snider J. Org. Chem.1981,46,3155. 29 L. M. Stephenson and M. Orfanopoulos J. Org. Chem. 1981,46 2220. Reaction Mechanisms -Part (i) Pericyclic Reactions 59 -31 cm3 mol-' (with hV = 27.0 f 0.5 cm3 mol-') confirming that the reaction is entirely ~oncerted.~' The thermal (120 "C) reactions of diethyl oxomalonate (34; E = C0,Et) and butyl N-(ptoluenesulphony1)iminoacetate (15)with enolizable ketones have been in~estigated.~~" The y-0x0-a-hydroxy-diestersand y-oxo-a- tosylamino-esters thus obtained may be regarded as arising from the formal ene additions of the above enophiles to the ketone enolates; there are precedents for such processes in the chemistry of 1,2,3-tricarbonyl systems (e.g. alloxan). The full paper on the thermal and Lewis acid-catalysed additions of (35) to olefins has now appea~ed;~" simple routes to a-amino-acids and y,S-unsaturated a-amino acids are outlined.Acylnitroso compounds (RCONO) are conveniently generated in situ by the decomposition of their (4 + 2) adducts with 9,lO-dimethylanthracene and are potent ene- and dien-~philes.~~ Thus formation of MeCONO in refluxing cyclo- hexene (an olefin of very moderate ene reactivity) afforded the hydroxamic acid ene adduct (36) in 85% yield.32" The reactions follow the expected regiochemistry of ene additions and appear to be kinetically controlled processes. An intramolecular variant of the affords a general approach to the cis-fused octahydroindole skeleton of Amaryllidaceae alkaloids and a synthesis of (f)-crinane is Reaction of diphenylphosphinodithioicacid with nitriles takes place in two steps the first being a formal ene reaction involving four heteroatoms as indicated by (37).33 Treatment of ethyl a-methylsulphinylacetate with trifluoroacetic anhydride OAIMe2CI fo2Bu N 0 EKE Tos/ R3 (1equiv.) in trifluoroacetic acid solution affords the Pummerer reaction intermediate (38) which may be intercepted by added alkenes to give ene adducts for example (39) from ~ent-l-ene.~~ The HOMO energy of 1,l'-bicyclopropylidene is about 0.59 EV higher than that of the (very ene reactive) parent methylenecyclopropane.30 M. Papadopoulos and G. Jenner Tetrahedron Lett. 1981 22 2773 31 (a)0.Achmatowicz jun. and M. Pietraszkiewicz Tetrahedron Lett. 1981 22,4323; (b)J.Chem. SOC. Perkin Trans. 1 1981 2680. 32 (a)G. E. Keck R. R. Webb and J. B. Yates Tetrahedron 1981 37 4007; (b)G. E. Keck and R. R. Webb J. Am. Chem. SOC.,1.981 103 3173. See also P. Horsewood G. W. Kirby R. P. Sharma and J. G. Sweeny J. Chem. SOC.,Perkin Trans 1 1981 1802 and G. W. Kirby and J. G. Sweeny ibid. p. 3250. 33 S. A. Benner Tetrahedron Lett. 1981 22 1855. 34 Y. Tamura H.-D. Choi H. Maeda and H. Ishibashi Tetrahedron Lett. 1981 22 1343 60 G.B. Gill + + MeSCHC0,Et +B MeS=CHC02Et + Addition to tetrachlorocyclopropene occurs at 80 "C to give (41) which is presum- ably derived from (40) the product of an ene-type addition involving chlorine-atom transfer.35 4 Sigmatropic Rearrangements The [ 1,5] shifts of H and substituent groups primarily in cyclic unsaturated systems have been reviewed.36 A [1,5] shift of a silyl group from oxygen to carbon has been observed; on heating (42) to 120 "C (1h) smooth rearrangement occurred to give (40) (41) (42) the a,P-unsaturated ester." The normal direction of the [1,5] homodienyl H shift (43a) (44a) in which strain effects shift the equilibrium to favour the acyclic diene can be reversed if the allylic C atom from which the H-transfer occurs in (43) is substituted by an OH group i.e.(43b) $ (44b) $ (45).38 Thermochemical calculations reveal that (43b) -+ (45) is exothermic (AAH = -8.8 kcal mol-') whereas for (43a) + (44a) the process is endothermic (AAH = +6.4 kcal mol-'). The procedure can be employed for stereoselective cyclopropane synthesis.(43) a; X = H (45) b;X=OH Substituent effects in aliphatic Claisen rearrangements have been studied and the results rationalized in terms of HMO For the rearrangement of a monosubstituted ally1 vinyl ether (46) the predictions are that the rearrangement should be accelerated (relative to the unsubstituted case) for a donor substituent at positions 1 2 or 3 and an acceptor substituent at positions 2 3 or 4. A chair conformation is assumed except in the case of an acceptor substituent at position 4 when a half-chair conformation is predicted to lower AH' for reaction. The 35 W. Weber U. Behrens and A. de Meijere Chem. Ber. 1981,114 1196. 36 V.A.Mironev A. D. Fedorovich and A. A. Akhrem Usp. Khim. 1981,50 1272. 37 G. Anderson D. W.Cameron G. I. Feutrill and R. W. Read TetrahedronLett. 1981,22,4347. 38 F.-G. Klarner W. Rungeler and W. Maifeld Angew. Chem. Int. Ed. Engl. 1981 20 595. 39 C. J. Burrows and B. K. Carpenter J. Am. Chem. SOC., 1981 103,6983,6984. Reaction Mechanisms -Part (i) Perk yclic Reactions regioselectivities of the photochemical [1,7] sigmatropic shifts and electrocycliz- ations of substituted cycloheptatrienes can be explained in terms of an excited singlet-state model in which a 90" rotation about a terminal bond is accompanied by 'sudden polarization' to form a zwitterionic species.4o Thus for a 2-substituted cycloheptatriene the presence of a pentadienyl anion-stabilizing substituent (accep- tor) favours polarization as indicated in (47) hence leading to 1,4-electrocyclization and 7 + 1sigmatropic shift.On the other hand a donor 2-substituent destabilizes the pentadienyl anion thereby favouring the cross-conjugated polarization of (48); this should lead to 3,6-electrocyclization and 7 + 6 sigmatropic shift. Secondary kinetic hydrogen-isotope effect at the side-chain p carbon atom in phenyl allyl sulphide and the effect of para-substituents on rate have been examined in a study of nucleophilic catalysts of the thio-Claisen rearrangement.41 The results (k,/k = 1.05 and log kpPx/kH = 0.250') support the mechanism involving nucleophilic triggering of the sigmatropic rearrangement. (46) (47) (48) The recently (1980) reported (PhCN),PdCl,-catalysed Cope rearrangement of acyclic 1,5-dienes by way of complexed cyclohexyl carbonium ion as the proposed intermediate is now thought instead to occur by way of the bis(q3-allyl) complex (49).42Thus treatment of hexa-1,5-diene vapour with an aqueous solution of (PhCN),PdCl, CuCl, and CuCl at 60°C in a stream of excess oxygen gave substantial catalytic conversion to acetone (Wacker oxidation).The organo- aluminium reagents Et,AlSPh or Et,AlCl-PPh have been found to be effective for promoting the Claisen rearrangement of allyl vinyl ethers to y,&unsaturated aldehydes and ketones without competing nucleophilic addition to the carbonyl carbon atom. With Et,Al for example both Et and H addition to the aldehyde carbon atom occur.43 The Cope rearrangement of 1,5-dienes possessing an acyl group at the 2-position is strongly accelerated by protonic and Lewis acids e.g.(50) +(51).44 pPd x-(yJ+(y-\/ /\ CI CI Me Me (49) (50) (5 1) 40 T. Tezuka 0.Kikuchi K. N. Houk M. N. Paddon-Row C. M. Santiago N. G. Rondan J. C. Williams jun. and R. W. Gandour J. Am. Chem. Suc. 1981,103 1367. 41 H. Kwart W. H. Miles A. G. Horgan and L. D. Kwart J. Am. Chem. Suc. 1981,103 1757. 42 R. Hamilton T. R. B. Mitchell and J. J. Rooney J. Chem. Suc. Chem. Commun. 1981,456;see also J. Muzart P. Pale and J.-P. Pete ibid. p. 668. 43 K. Takai I. Mori K. Oshima and H. Nozaki Tetrahedron Lett. 1981,22 3985. 44 W. G.Dauben and A. Chollet Tetrahedron Lett. 1981 22 1583. 62 G. B. Gill Removal of the development of repulsive interactions in a boat transition state for the Cope rearrangement leads to a marked reduction in the activation energy.Thus both (52)45 and (53)46 undergo [3,3] shifts with remarkably low activation energies; the rearrangement of (52) is reversible. (52) (53) The alkoxide-accelerated [1,3]migration (54) -+ (55) is 75% intramolecular and 25YO intermolecular. When allowance is made for the intermolecular process rearrangement is found to occur with at least 65% retention of configuration. Although fragmentation-recombination within a solvent cage cannot be ruled out the above observation is consistent with the hypothesis that 'any substituent will accelerate a forbidden pericyclic reaction more than it accelerates the corresponding allowed reaction' because of the strong interaction with the essentially antiaromatic orbital array at the transition state (i.e.high HOMO and low LUM0).47The fraction of the rearrangement of the cyclononatrienols (56; R = Me or Et) which passes through the oxy-Cope pathway increases (relative to [1,3] rearrangement) as the donor properties of the oxygen atom are decreased (K' -+Na' -+ H) with a reduction in rate of is~merization.~~ The Li' and K' salts of 2-vinylcyclobutanols undergo [1,3] rearrangement at 25-70 "C,giving cyclohexen-3-01 derivative^.^^ The suprafacial-inversion pathway predominates when the alkoxide substituent and vinyl group are trans whereas the (slower) suprafacial-retention mode is involved when these two groups are cis to one another.The means whereby ring expansion by eight carbon atoms can be achieved by alkoxide-accelerated [5,5] or two consecutive [3,3] shifts have been dis~losed.~" The [2,3] sigmatropic rearrangement of the cis-and trans-isomers of spirocyclic sulphonium ylides (57) gives respectively cis and trans doubly bridged S-heterocyclic ethylene~.~~ -)Ph .() 0-K+ -0:. ekY ?H K+-O ':LPh 0 tQ= H / (54) (55) (56) (57) 45 K.B. Wiberg M. Matturro and R. Adams J. Am. Chem. SOC.,1981,103,1600. 46 Y. Tobe F. Hirata K. Nishida H. Fujita K. Kimura and Y. Odaira J. Chem. SOC., Chem. Commun. 1981,786. 47 M. T. Zoeckler and B. K. Carpenter J. Am. Chem. SOC.,1981,103,7661. 48 G. D. Crouse and L. A. Paquette Tetrahedron Lett. 1981 22 3167. 49 R. L. Danheiser C. Martinez-Davila and H.Sard Tetrahedron 1981 37 3943. 50 P. A. Wender and S. McN. Sieburth Tetrahedron Lett. 1981 22 2471; P. A. Wender S. McN. Sieburth J. J. Petraitis and S. K. Singh Tetrahedron 1981 37 3967. 51 V. Cere C. Paolucci S. Pollicino E. Sandri and A. Fava J. Org. Chem. 1981 46 486; see also ibid. p. 3315. Reaction Mechanisms -Part (i) Pericyclic Reactions 5 Electrocyclic Reactions Replacement of an olefinic carbon atom in cyclobutene by an N-oxide imino function has a relatively small effect on the activation energy for ring opening without alteration of the stereochemical pathway; thus (58) + (59) with AH*= 27 f 1kcal mol-’ and AS* = -2 f3 e.u.” Dehydrochlorination of N-chloroazetidine in the vapour phase over silica-supported Bu‘OK at 94 “C affords Me 70 phF N<m 2 + PhXNyMe H Me H CO I NEt (58) (59) 1-azetine almost quantitatively which on flash vacuum pyrolysis is converted into 2-a~abutadiene.~~ Eliminative processes have been employed to generate oxete and 3-phenyloxete both of which ring-open at 25°C to the corresponding a,@-unsaturated aldehydes (ti = ca.8.4 hand 14 h re~pectively).~~ Infrared multiphoton excitation has been employed successfully for the selective isomerization of 2- methyl- and 2,3-dimethylbuta-1,3-diene to the corresponding cyclobutenes (respec- tively AH = +10.6 and +9.6 kcal mol-1 and AS = -3.9 and -3.6 e.u.). By shifting the irradiating frequency the cyclobutenes can be efficiently and cleanly ring- opened.” Vibrational excitation of the gound electronic state of cis-3,4-dichloro- cyclobutene by an intense infrared laser leads to a substantial increase in the yield of the symmetry-forbidden products; precise mechanisms are not yet knowns6 Irradiation of the enedione (60) at 77 K in a hydrocarbon glass with light of wavelength 240-400 nm afforded CO and a labile compound identified from its spectral characteristics as norcaradiene (61).s7The kinetics of the isomerization of (61) into cycloheptatriene were measured at ca.100 K by monitoring the increase in optical density at 261 nm giving good first-order behaviour with k = (6.0 0.3) 1011e(-6500*1000)/RT . Estimates for the room temperature (25°C) isomerization give a rate constant of 1 x lo7s-’ with AS* = -4.5 e.u. and AG* = 7.2 kcal mol-’.Whereas 1,3,5-cyclo-octatriene is favoured with respect to its valence isomer cis,cis-l,3,5,7-octatetraene,the bicycle (62) is more stable than its tricyclic conrota- tion product (63). Presumably the inherent instability of the central cyclobutadiene ring in (63) is responsible for the differences in behavio~r.~’ Further details on the photochromic behaviour in the electrocyclization of substituted (E)-3-furylethyl- idene(isopropy1idene)succinic anhydrides (i.e. fulgides) have appeared,59 as have 52 M. L. M. Pennings D. N. Reinhoudt S. Harkema and G. J. van Hummel J. Am. Chem. SOC.,1980 102,7570. ” J. C. Guillemin J. M. Denis and A. Lablanche-Combier J. Am. Chem. SOC.,1981 103,468. ” L. E. Friedrich and P. Y.-S. Lam J. Org. Chem. 1981,46 306. ” J.L. Buechele E. Weitz and F. D. Lewis J. Am. Chem. SOC.,1981 103 3588. 56 C. R. Mao N. Presser L.-S. John R. M. Moriarty and R. L. Gordon J. Am. Chem. SOC.,1981 103 2105. 57 M. B. Rubin J. Am. Chem. SOC.,1981,103,7791. H. Meier T. Echter and 0.Zimmer Angew. Chem. Znt. Ed. Engl. 1981,20 865. 59 H. G. Heller and S. Oliver J. Chem. SOC.,Perkin Trans. 1 1981 197; P. J. Darcy H. G. Heller P. J. Strydom and J. Whittall ibid. p. 202. 64 G. B. Gill (60) (61) (62) (63) the results on the thermal isomerization of cyclic cis,truns,cis-trienes where it is demonstrated that there is a structure-reactivity correlation between the size of the ring and the type of product observed.60 Because of the coiled geometry the proximity of the Me group to the n-system in truns,cis,truns-cyclononatriene(64) has an acidifying effect on its H atoms.The HOMO of the derived anion (KH in THF containing 18-crown-6 at 20 "C)has an in-phase relationship with the closely located terminal p-IT lobes and the system is ideally set up for antarafacial electrocyclization which affords bicyclor4.3. lldeca- 2,4-diene by way of the bicyclic anion (65).61With the ethyl and benzyl analogues of (64) the exocyclic group at C-10 in the final product is syn to the diene unit. The vinylogous sesquifulvalene (66) underwent thermal electrocyclization (E = 100 kJ mol-' log A = 12.0) perispecifically in the symmetry-forbidden conrotatory mode to give (67) which is rapidly isomerized to aromatic [1,5] H-shift products. The trans-stereochemistry of (67) was verified by X-ray crystallographic analysis of its adduct with dimethyl acetylenedicarboxylate.62 6o W.G. Dauben D. M. Michno and E. G. Olsen J. Org. Chem. 1981,46,687. " L.A.Paquette and G. D. Crouse J. Am. Chem. Soc. 1981,103,6235. H. Prinzbach H. Bingmann A. Beck D. Hunkler H. Sauter and E. Hadicke Chem. Ber. 1981 114 1697.