4 Reaction Mechanisms Part (i) Pericyclic Reactions By R. J. BUSHBY Department of Organic Chemistry The University Leeds LS2 9JT 1 Introduction The pericyclic reactions of singlet oxygen' and of the photoexcited states of organic anions2 have been reviewed. The effect of substituents on pericyclic reactions has long remained a source of difficulty. This year two interesting approaches to the problem have been described. Carpenter and Wilcox3 have used a simple HMO model. They have shown that for electrocyclic reactions 1,5-hydrogen shifts cyclopropane stereomutations and reactions involving carbon-carbon bond homolysis there is a linear relationship (1) between AAH* (the measured effect of the substituent on the enthalpy of activation in kcal mol-l) and AAE (the calculated difference between the effect of the substituent on the HMO .rr-energy of the substrate and that of a suitable model for the transition state both in units of p.Mobius cyclobutadiene is taken as a model for the transition state in the conrotatory opening of cyclobutene). AAP = 19.31AAE (1) In most cases deviations from linearity are small. For example the effects of phenyl substituents on the enthalpy of activation for opening the cyclobutenes (2) (3) and (4)[relative to the parent system (l)] are calculated from equation (1)to be -7.0 -12.0 and +7.0 kcal mo1-l respectively whereas the measured values are -6.3 -11.2 and +6.4 kcal mo1-l. The treatment is limited to hydrocarbon systems and breaks down for reactions such as 3,3-sigmatropic rearrangements where the substituents themselves drastically alter the position and nature of the transition state.This variable nature of the transition state in Cope/Claisen rearrangements is 4 phj-yph A. A. Frimer Chem. Rev. 1979,79,359. M. A.Fox Chem. Rev. 1979,79,253. C. F. Wilcox and B. K. Carpenter,J. Amer. Chem. SOC.,1979,101 3897. R. J. Bushby deliberately built into the model developed by Gaje~ski.~ He makes use of the simplest equation for an energy surface with a saddle point; namely equation (2) in which for 3,3-sigmatropic shifts x and y refer to the fraction of 1,6-bond formation and 3,4-bond breaking and a b c and d are constants. AG = ax +by +cxy +d (2) Application of suitable boundary conditions and solution for the position of the saddle point gives rise to equation (3) in which AG* is the desired free energy of activation AG’(BB) and AG’(BM) are the calculated free energies for forming the (appropriately substituted) bond-broken and bond-made species (5) and (6) AGr is the free energy of reaction and p is an empirically derived parameter which is found to be constant for a given series of reactions.For a value of p = 1.5 this equation leads to predicted free energies of activation for the 3,3-sigmatropic rearrangements of the dienes (7) (8) and (9) of 41.2 36.3 and 30.1 kcal mol-’ respectively whereas the experimental values are 41,35.5 and 31 kcal mol-’. A similar treatment was applied successfully to the Diels-Alder reaction of cyano-substituted dienophiles.0 ;c; w (5) (6) (7) (8) Ph (9) 2 Cycloadditions and Cycloreversions Charge-transfer complexes are frequently formed between compounds which undergo cycloaddition reactions but it is difficult to decide whether these are intermediates [equation (4)] or just a dead end [equation (5)]. Reactants $Charge-transfer complex +Cyclo-adducts (4) Charge-transfer complex ++Reactants -+Cyclo-adducts (5) Hence one study of the addition of tetracyanoethylene to vinyl ethers suggests that the charge-transfer complex is a true intermediate5 and another very similar study that it is Perhaps the best evidence for the intermediacy of a charge-transfer complex comes from the reaction of tetracyanoethylene with 9,lO-dimethylanth- racene where the observed ‘overall’ enthalpy of activation is negative.’ This can only be reconciled with equation (4) and a more recent study of the reaction of tetracyanoethylene with a range of anthracene derivatives has shown a correlation J.J. Gajewski J. Amer. Chem. SOC.,1979 101,4393. M. Sasaki H. Tsuzuki and M. Okamoto J. Org. Chem. 1979,44,652. J. von Jouanne H. Kelm and R. Huisgen J. Amer. Chem. SOC.,1979,101,151. ’V. D. Kiselev and J. G. Miller J. Amer. Chem. SOC.,1975 97 4036. Reaction Mechanisms -Part (i) Pericyclic Reactions between the 'overall' free energy of activation and that for formation of a charge- transfer complex. This has also been interpreted as evidence that the charge-transfer complex is a true intermediate.8 The formation of zwitterionic intermediates in certain cycloaddition reactions has continued to attract attention and Moore9 has discussed the use of furanone azides for the independent generation of such intermediates.For example the furanone (10) can be used to generate the zwitterion (ll),which is thought to be an intermediate in the addition of cyanochloroketen to benzaldehyde." Evidence has also been provided for a zwitterionic intermediate in the addition of tetra-cyanoethylene to thioenol ethers," and the zwitterionic intermediate (12),formed by the addition of bromoketen diethyl acetal to an electron-poor olefin is trapped internally to give (after work-up) the cyclopropane (13).'* 0-CO),Et N3 cl)j$ Ph C0,Et (13) Several investigations have been reported of the 2 +2 Lewis-acid-catalysed addition of propiolate esters to alkene~.'~ Whilst the mechanism of this reaction is still uncertain the observed stereospecificity as well as the parallels with keten reactivity suggest a concerted 7~2s+7~2a process.[Perhaps the keten analogy is best seen if the intermediate complex is written as in formula (14)].However the reaction with norbornene gives both normal (15) and rearranged (16)products showing that a zwitterionic intermediate can be formed when the carbonium ion is sufficiently stable. Some 2 +4 cycloaddition reactions are also catalysed by Lewis acids; when the chiral menthol derivative (17)is employed quite high asymmetric induction can be ~btained.'~ RO ,OAlCI II &C0,Me C C /I +CH M.Lofti and R. M. G. Roberts Tetrahedron 1979,35 2131 2137. H. W. Moore Accounts Chem. Res. 1979,12,125. lo H. W. Moore F. Mercer D. Kunert and P. Albaugh J. Amer. Chem. SOC.,1979,101,5435; but compare 0.Krabbenhoft,J. Org. Chem. 1978,43,1305 and E. Schaumann and J. Ehlers Chem. Ber. 1979,112 1000. l1 R. Huisgen and H. Graf J. Org. Chem. 1979,44 2594 2595. l2 H. K. Hall A. B. Padias A. Deutschmann and I. J. Westerman J. Org. Chem. 1979,44,2038. l3 B. B. Snider and D. M. Roush J. Amer. Chem. SOC.,1979,101,1906; B. B. Snider D. J. Rodini R. S.E. Conn and S. Sealfon ibid. p. 5283; R. D. Clark and K. G. Untch J. Org. Chem. 1979 44 248; H. Fienemann and H. M. R. Hoffmann ibid p. 2802. l4 S. Hashimoto N. Komeshina and K. Koga J.C.S. Chem. Comm. 1979,437.R. J. Bushby The energetics for the gas-phase retro-Diels-Alder reactions of 3,6-dihydro-2H- pyrans seem to exclude the possibility that biradicals are intermediates." For example the observed energy of activation for the parent compound (18) is 49.7 kcal mol-l whereas formation of biradical (19) would require ca. 66.0 and of the biradical(20) ca. 69.3 kcal mol-'. OAc 1 The stereochemistry of the product (2 1)obtained by allowing 1-acetoxybutadiene and dimethyl fumarate to react had been explained in terms of secondary orbital interactions. However investigation of addition reactions of a range of fumaric acid derivatives shows exceptions to the expected stereochemical pattern. It has there- fore been concluded that if the secondary orbital effects are ever significant in these systems then they are small and easily over-ridden by other factors.16 On the other hand the preference of N=N dienophiles for the syn face of propellane (22) [leading to adducts such as (23)] and of C=C dienophiles for the anti face [leading to adducts such as (24)] has been plausibly explained in terms of a secondary orbital interaction between the antisymmetrical combination of the lone-pair orbitals of the N=N and the .;rr*-orbitals of C=O which attracts this dienophile to the syn side." 0 (22) X = 0,NH or NR (23) 0 (24) Two investigations of the Diels-Alder reaction have been made in which it is claimed that reactivity is related to the C-1-C-4 distance in the diene as well as to the ionization potential of the diene.'* Similar studies of 1,3-dipolar cycloadditions have nicely illustrated how the electron-rich/-poor nature of the 1,3-dipole influences the relationship between ionization potential and reactivity of the alkene.Whereas diazomethane is of 'type 1'in Sustmann's classification (reaction being controlled by the HOMO of the 1,3:dipole and the rate increasing roughly as the ionization potential of the alkene increases) in diazoacetic ester (25b) 'type 2' behaviour is H. M. Frey R. Pottinger H. A. J. Carless and D. J. Lingley J.C.S.Perkin II,1979,1460; H. M. Frey and S. P. Lodge ibid. p. 1463. W. B. T. Cruse I. Fleming P. T. Gallagher and 0.Kennard J. Chem. Res. (3, 1979,372. l7 M. Kaftory M. Peled and D. Ginsburg Helv. Chim. Acta 1979,62 1326.H.-D. Scharf H. Plum J. Fleischhauer and W. Schleker Chem. Ber. 1979,112,862;R. Sustmann M. Bohm and J. Sauer ibid. p. 883. l9 (a) J. Geittner R. Huisgen and R. Sustmann Tetrahedron Letters 1977 881; (b) W. Bihlmaier R. Huisgen H.-U. Reissig and S. Voss ibid. 1979 2621. Reaction Mechanisms -Part (i) Pericyclic Reactions observed [interactions with the HOMO and the LUMO of the 1,3-dipole are both important leading to a U-shaped plot of log (rate) vs. (ionization potential of the alkene)] and the introduction of further electron-withdrawing groups as in dimethyl diazomalonate (25c) or methyl diazo(phenylsulphony1)acetate (25d) leads to behaviour intermediate between ‘type 2’ and ‘type 3’”’ (Sustmann ‘type 3’ behaviour involves domination by the LUMO of the 1,3-dipole and a rate of reaction which increases as the ionization potential of the alkene decreases).A similar difference is seen between benzene nitrile oxide (26a) which shows ‘type 2’ behaviour and the more electron-deficient benzenesulphonyl nitrile oxide (26b) which shows behaviour intermediate between ‘type 2’ and ‘type 3’.20 R’ \-+ O-&fC-R R2/c-N=N (25) a; R’=R2=H (26) a; R=Ph b; R’ =H R2 = C02Me b; R=SO;?Ph c; R’ = R2= C02Me d; R’ = C02Me R2= S02Ph Retro- 1,3-dipolar additions2’ and the cycloaddition reactions of triazines2* have been reviewed. Katritzky and co-workers have continued their extended studies of aromatic ring 1,3-dipoles. 1-Substituted-3-oxido-pyridiniums (27)give adducts (28) with alkenes and it has been shown that reactivity and selectivity can be rationalized in terms of FMO Ab initio MO calculations (STO-3G and 4-31G) on the thermal elimination of nitrogen from A’-pyrazolines suggest a non-synchronous breaking of the two carbon-nitrogen bonds and (probably) a nitrogen-containing biradical inter- mediate.24 The pyrolysis of tetrahydropyridazines (29) and N-pyrrolidine nitrenes (30) as well as the thermal rearrangement of cyclobutanes has generally been interpreted in terms of a common 1,4-biradical although there is also evidence for a direct retro-(2+2 +2) fragmentation of the dia~ines.~’ 2o P.A. Wade and H. R. Hinney Tetrahedron Letters 1979 139. ” G. Bianchi C. De Micheli and R. Gandolfi Angew. Chem. Internat. Edn. 1979,18,721.22 J. Bourgois M. Bourgois and F. Texier Bull. SOC. chim. France 1978,1I 485. 23 A. R. Katritzky N. Dennis M. Chaillet C. Larrieu and M. El Mouhtadi,J.C.S. Perkin I 1979,408 and related papers. 24 P. C. Hiberty and Y. Jean J. Amer. Chem. SOC. 1979,101,2538. 2s P. B. Dervan T. Uyehara. and D. S. Santilli J. Amer. Chem. Soc. 1979,101,2069; P. B. Dervan and T. Uyehara ibid. p. 2076; P. B. Dervan and D. S. Santilli ibid. p. 3663. R. J. Bushby 3 Sigmatropic Rearrangements The stereochemistry of 2,3-sigmatropic rearrangements has continued to attract and has been reviewed,28 as has anchimeric assistance by silicon and its relevance to the mechanism of dyotropic rearrangement^.^' The phototranspositions of cyano-thiophens [for example the conversion of compound (31) into its isomer (32)] have been shown to involve 5-thiabicyclo- [2.1.0]pent-2-ene intermediates [(33) and (34) in the example given] which Me CN MP MeMcNMe interconvert via a sulphur ‘walk’.In some cases it has been shown that these intermediates can be trapped as their 2+4 furan adducts or as in the case of compound (33) isolated from the reaction mixture so that the sulphur ‘walk’ can be studied in i~olation.~’ An interesting related carbon ‘walk’ [bicyclopentene (35) to its isomer (36)] has also been reported.31 This thermal 1,3-shift involves inversion at the migrating centre as expected for an orbital-symmetry-controlled process. However the 1,3-shift in compound (39 the related 1,5-shifts in compounds (37) and (38) 32 and the 1,7-shift in compound (39)33 all apparently involve inversion at the migrating centre whether this is ‘allowed’ or not.The simplest view of these results is that the stereochemistries are determined by ‘least motions’ factors and that the distinction between ‘allowed’ and ‘disallowed’ processes is found not in the stereochemistries but in the activation energies which are 21.7 37.1 ca. 35 and 28.8 kcal mol-’ for compounds (33 (37) (38) and (39)respectively. However by using a specifically deuteriated 3,7-dimethyl-7-methoxymethylcycloheptatriene Baldwin claims to have shown that the 1,5-shift occurs by a two-step (C-7 epimerization) + (1,5-shift with retention) ‘allowed’ It is also found that ($C02Me -Ma#co2Me R2Me / & Me Me 26 E.Vedejs M. J. Arnost and J. P. Hagen J. Org. Chem. 1979,443230; V. Cert C. Paolucci,S. Pollicino E. Sandri and A. Fava ibid. p. 4128. ’’ E. Vedejs M. J. Arco D. W. Powell J. M. Renga and S. P. Singer J. Ore. Chem. 1978.43.4831; V. Cer6 C. Paolucci S. Pollicino E. Sandri and A. Favo ibid. p. 4826. 28 R. W. Hoffmann Angew. Chem. Internat. Edn. 1979,18,563. 29 M. T. Reetz Angew. Chem. Internat. Edn. 1979,18 173. 30 J. A. Barltrop A. C. Day and E. Irving J.C.S. Chem. Comm. 1979 881 966. 31 F.-G. Klarner and F. Adamsky Angew. Chem. Internat. Edn. 1979,18,674. 32 (a)F.-G.Klarner S. Yaslak and M. Wette Chem. Ber. 1979,112 1168; (b) J. E. Baldwin and B. M. Broline J. Amer. Chem. SOC.,1978,100 4599. Reaction Mechanisms -Part (i) Peric yclic Reactions 51 the photochemical rearrangements of compounds (37) and (38) like their thermal analogues involve overall inversion of the migrating Here epimerization at C-7 certainly competes with the 1,5-shift and the results have been interpreted in terms of a triplet biradical intermediate (40) which can either close or in which rotation about the C-6-C-7 bond occurs.Me 7 X Y (39) (40) X = C02Meor CN Migratory aptitude in 1,5-sigmatropic shifts seems to be determined by a number of factor^.^'-^^ Dolbier and his co-workers have shown that the isoindenes (41) [normally encountered as short-lived intermediates in the rearrangement of indene~~~] can be generated by eliminating N,O from the corresponding bicyclo- azoxy-system (42).35*39 They have studied the relative migratory aptitudes of the substituents R in these compounds seeking for evidence of a radical-pair mechanism.Whilst on quantitative grounds they demonstrated that the extent of radical development cannot be very great they did find a correlation between migratory aptitude and the stability of the radical (R). In other systems secondary orbital interactions seem to be important; for example in the migration of carbonyl groups. Whereas 1$shifts of alkyl groups in cyclopentadienes frequently require temperatures above 300 "C the rate of rearrangement of the formyl-substituted compound (43)is rapid (k= 90 s-l) at room tempe~ature.~' Here the transition state can be stabilized by an interaction between (1/3 of the pentadienyl system and T*of the formyl group (44).A complementary situation is seen in the rapid 1,5-shift of the carbanionic centre in compound (49 where a similar interaction may be written between t,h4 of the pentadienyl system and a filled p-orbital of the carbanion (46).38 33 F.-G. Klarner and M. Wette Chem. Ber. 1978,111 282. 34 F.-G. Klarner and S. Yaslak Chem. Ber. 1979,112 2286. 35 W. R. Dolbier K. E. Anapolle L. McCullagh K. Matsui J. M. Riemann and D. Rolison J. Org. Chem. 1979,44,2845. 36 D. J. Field and D. W. Jones J.C.S. Perkin I 1979 1273. 37 R. J. Bushby and D. W. Jones J.C.S. Chem. Comm. 1979,688. 38 G. Boche and D. Martens Chem. Ber. 1979,112 175. 39 W. R. Dolbier K. Matsui H. J. Dewey D. V. Horik and J. Michl J. Amer. Chem. Soc. 1979,101,2136.R. J. Bushby Li CN CN There have been several attempts to demonstrate carbon analogues (47) of the Claisen rearrangement.4043 Such reactions can be facilitated by incorporating a cyclopropane ring into the system as in compound (48).41 The general difficulty of these reactions and the need to add a base catalyst had been attributed to a mechanism in which the rate-determining step is prototropic rearrangement of the intermediate (49). However the lack of scrambling of the isotopic label in compound (50) has been taken to indicate that the first step (3,3-shift) and not the second step (prototropy) is rate-determini~~g.~~ Evidence for a 1,4-diyl(52) in the Cope rearrangement of the en-yn-ene (51)has been provided by isolating products from the 1,2-silicon shift shown in (52).44 However secondary isotope effects for and aliphatic46 Claisen rear- rangements do not support the notion of a 1,4-diyl in these reactions.Rather they suggest a non-synchronous concerted process in which bond breaking is in advance of bond making. As expected they indicate that the transition state comes early in the more exothermic aliphatic rearrangement but later in the aromatic case. 40 G. Maas and M. Regitz Angew. Chem. Internat. Edn. 1977,16,711. 41 E. N. Marvell and C. Lin J. Amer. Chem. SOC., 1978 100 877; E. N. Marvell and S. W. Almond Tetrahedron Letters 1979,2777 2779. 42 J. B. Lambert D. M. Fabricius and J. A. Hoard J. Org. Chem. 1979,44 1480. 43 J. B. Lambert D. M. Fabricius and J.J. Napoli J. Amer. Chem. SOC.,1979,101 1793. 44 G. C. Johnson J. J. Stofko T. P. Lockhart D. W. Brown and R. G. Bergman J. Org. Chem. 1979,44 4215. 45 K. D. McMichael and G. L. Korver J. Amer. Chem. SOC., 1979,101,2746. 46 J. J. Gajewski and N. D. Conrad J. Amer. Chem. SOC.,1979 101 2747,6693. Reaction Mechanisms -Part (i) Pericyclic Reactions 53 Me3s$3Bu Bu‘ Stereochemical and regioselective aspects of the photochemical di-T-methane rearrangement have continued to excite interest:’ and the interconversion of compounds (53)and (54) has provided the first example of a thermal reaction of this type.48 D 4 Electrocyclic Reactions The electrocyclic reactions of 1,5-dipoles have been reviewed49 and those of radical cations discussed in some detail.50 The 16~-electron vinylogous heptafulvene (55)51cyclizes thermally in a conro- tatory manner to give compound (56).Whilst this is the stereochemistry expected for an ‘orbital-symmetry-controlled’ process the related l4r-electron and 12~-elec- tron compounds (57)52and (58)53also cyclize in a conrotatory sense despite the fact (57) (58) 47 H.E. Zimmerman and D. R. Diehl J. Amer. Chem. SOC.,1979 101 1841; H. E. Zimmerman T. P. Gannett and G. E. Keck J. Org. Chem.,1979,44,1982;R. L. Coffin,W. W. Cox R. G. Carlson andR. S. Givens J.Amer. Chem. SOC.,1979,101,3261;L. A. Paquette A. Y. Ku C. Santiago M. D. Rozeboom and K. N. Houk ibid.,p. 5972; A. Y. Ku L. A. Paquette M. D. Rozeboom and K. N. Houk ibid. p. 5981; A. Padwa and T.Brookhart J. Org. Chem. 1979,44,4021. 48 M. Demuth U. Burger H. W. Mueller and K. Schaffner J. Amer. Chem. SOC.,1979 101 6763; M. Demuth C. 0.Bender S. E. Braslavsky H. Gorner U. Burger W. Amrein and K. Schaffner Helu. Chim. Actu 1979,62 847. 49 E. C. Taylor and I. J. Turchi Chem. Rev. 1979,79 181. E. Haselbach T. Bally and Z. Lanyiova Helu. Chim. Actu 1979 62 577; E. Haselbach T. Bally Z. Lanyiova and P. Baeryschi ibid.,p. 583. 51 H. Bingmann L. Knothe D. Hunkler and H. Prinzbach Tetrahedron Letters 1979 4053. ’* H. Prinzbach H. Babsch and D. Hunkler Tetrahedron Letters 1978,649. 53 H. Prinzbach H. Sauter and B. Gallenkamp Chem. Ber. 1977,110 1382. R. J. Bushby that compound (57) ‘should’ cyclize in a disrotatory manner. Since all three sub- strates probably adopt a spiral conformation the products obtained in each case are those expected on a ‘least motions’ basis.Probably the stereochemistries of these reactions are therefore the result of ‘least motions’ rather than ‘orbital symmetry’ control. There may however be some evidence for a weak alternation between what is ‘allowed’ and what ‘disallowed’ in the Arrhenius activation energies which are 20.0 24.4 and 22.1 kcal mol-’ for compounds (55)’ (57),and (58)respectively. It has been claimed that the cyclopropyl anion opens photochemically in a disrotatory manner.54 However the tendency of the products to undergo (photo- chemical) cis-trans isomerization renders the result open to some doubt. Similar problems have frustrated attempts to observe directly the stereochemistry of the thermal ring-opening The apparently ‘disallowed’ cyclization product (60) obtained by allowing the cyclononatetraenyl anion (59) to react with elec- trophiles RX has now been shown to arise in an ‘allowed’ manner from the trans-isomer of the anion.56 (59) 54 1979,101,4008.M. A. FOX,J. Amer. Chem. SOC. 55 G. Boche K. Buckl D. Martens D. R. Schneider and H.-U.Wagner Chem. Ber. 1979,112,2961. 56 G. Boche M. Bernheim D. Lawaldt and R. Ruisinger Tetrahedron Letters 1979,4285.