4 Reaction Mechanisms Part (i) Pericyclic Reactions By C.I.F. WATT Department of Chemistry University of Manchester Manchester M 13 9PL UK 1 Diels-Alder Reactions Mechanistic Studies.-Rate Product and Stereochemical Studies. Secondary deuterium kinetic isotope effects have been calculated for concerted and stepwise pathways of [4+ 21 cycloadditions and cycloreversions using ab initio methods up to MCSCF/6-31G* levels. The expected effects for the two pathways are almost always sufficiently different to expect that experiment would distinguish between them. Available experimental data on a number of symmetrical or near symmetrical reactions have been collected and the concerted pathways give an excellent fit to the data. 14C kinetic effects for butadiene reacting with ethylene or acrolein were also calculated.' Complementary studies of the stereoselectivity and pressure dependence2 in the thermal dimerization of buta-l,3-diene (1) have demonstrated the value of activation volumes in distinguishing concerted and stepwise cycloadditions (Scheme 1 ).For formation of vinyl cyclohexene (2) the [4 + 21 product AV* is 13.3 cm3 mol- less than that for the competing [2 + 21 cyclization leading to trans-1,2-divinylcyclobutane (3). Studies with (2,2)-1,4-dideuteriobuta-l,3-dieneshow that the formation of the vinylcyclohexenes occurs with only 3% loss of stereochemistry at 1 bar and less than 1% at 7 kbar providing good evidence that formation of the [4+ 2) adduct does indeed proceed by a concerted mechanism with a small amount of competing stepwise reaction which is suppressed at high pressure.A similar study carried out with chloroprene and (E)-1-deuteriochloropreneyielded AV* = -22 cm3 mol- for for- mation of the isomeric divinylcyclobutanes (4)and one of the [4+ 2) adducts (5) which is formed non-stereospecifically. The conclusion is reasonable that these three products devolve from the same biradical intermediate. For the remaining two [4+ 21 adducts products (6) and (7) A V* = -29 and -3 1 cm3 mol- and these are formed by concerted cycloaddition. Activation volumes have also been determined for reaction of N-phenylmaleimide and isoprene in the presence of aluminium chloride or lithium per~hlorate.~ These are A V* = -42 and -45 cm3 mol- 'respectively and markedly more negative than the J.W. Storer L. Raimondi and K.N. Houk J. Am. Chern. Soc. 1994 116 9675. F.-G. Klarner B. Krwaczyk B. Ruster and U. K. Deiters J. Am. Chem. SOC. 1994 116 7645 N. S. Isaacs L. Maksimovic and A. Laila J. Chem. SOC. Perkin Trans. 2 1994 495. 51 C.I. F. Watt P \ Scheme 1 corresponding uncatalysed reaction which has A V = -36 cm3 mol- ’.The results are in accord with predictions assuming prior coordination of Lewis acid and the dienophile. The activation volume for reaction of N-ethylmaleimide and anthracene- 9-methanol is more negative in water than in non-aqueous medium. Medium and Substituent Eflects. Exo-endo equilibrium ratios but not kinetic selectivities of reactions in benzene of N-phenylmaleimide with a set of p-substituted 6-phenyl-6-methylf~lvenes~ show a linear free energy relationship with 0’ substituent parameters (p = -0.701).Reactivities gave a reasonable correlation with 6-with p = -0.684 but only when N(Me) and OMe are excluded from the substituent set. Solvent effects on reactivity and selectivity were small and not notably dependent on substituent. Solvent effects have also been examined in the reactions of 5-substituted naphthoquinones with cyclopentadienes.’ Substituent effects are attenuated in the more reactive solvents and give no indication that transition state charge separation in water differs from that in other solvents. However plots of activation energy against solvent E,(30) for reactions of 5-methoxynaphthoquinone gave indications that the slope of the LFER for a set of hydroxylic solvents including water was larger than for non-hydrogen-bonding solvents.Reactions of methyl vinyl ketone and methyl vinyl sulfone in the same set of solvents were also compared and medium effects separated into those on initial state and activated complex. Stabilization of the complex by 2,2,2-trifluoroethanol and destabilization of the ground state by water were notably larger for the ketone. The effects of pressure on Diels-Alder reactions of furans are higher in dichloromethane solution than in aqueous medium.6 Exo-endo ratios and regioselectivities in Diels-Alder additions of cyclopentadiene and isoprene to methyl vinyl ketone and methyl acrylate have been determined7 in eighteen pure solvents and in aqueous mixtures including some highly fluorinated alcohols.Correlations with a number of solvent parameters show that the endo+xo M. M. Gugelchuk P.-C.-M. Chan and T.J. Sprules J. Ory. Chem. 1994 59 7723. S. Otto W. Blokzijl and J.F.B. Engberts J. Org. Chem. 1994 59 5373. J. Jenner Tetrahedron Lett. 1994 35 1189. ’ C. Caticiela J. I. Garcia J.A. Mayoral and L. Salvatella J. Chem. Soc. Perkin Trans. 2 1994 847. Reaction Mechanisms -Part (i) Pericyclic Reactions selectivity is related mainly to solvophobic parameter (Abraham's S,) and donor bonding properties (a) while regioselectivity is linked strongly to hydrogen-bond donor ability. The importance of hydrogen bonding is also indicated by ab initio MO calculations' of the transition states for cyclopentadiene reacting with methyl vinyl ketone or acetonitrile in the presence of water molecules.Hydrogen bonding to oxygen or nitrogen of the dienophile is enhanced by about 1.5-2.0kcalmol-' over the ground-state interaction. Contributions from hydrophobic interactions are more modest. The effects of added salts on rates of Diels-Alder reactions in water correlate with their effects on the internal pressure of the medium Pi,and it has been pointed out that in reactions with negative activation volumes increases in the cohesive energy of the medium as measured by Pi are indeed expected to increase rate.' Chiral Processes.-Control of stereochemistry at new chiral centres in cycloadducts is a focus of synthetic interest and can be achieved either by use of chiral dienes and dienophiles or more elegantly by use of achiral components with a chiral catalyst.Developments in both areas are reported. Chiral Components and Auxiliaries. Chiral dienophiles include esters of 2-cyanocin-namic acid with ethyl (S)-lactate or (R)-pantolactone which react with butadiene in presence of titanium tetrachloride with high and complementary diastereoselectivi- ties.' A number of chiral2-nitro-1-sulfinylalkenes undergo stereoselective Lewis acid catalysed Diels-Alder reactions with cyclopentadiene,' ' with 2-sulfinyl dienophiles generally showing higher diastereo and endo selectivity. Tetra-substituted dienophiles required high pressure for action. Diacrylate esters of a C symmetrical chiral auxiliary give Diels-Alder adducts with a range of cyclic and acyclic dienes with high stereoselectivity in ethylaluminium dichloride catalysed reactions.I2 Amongst chiral dienes used were homochiral esters of 2-pyrone-3-carboxylic acids which react with enol ethers in presence of catalytic amounts of some lanthanide shift reagents to give adducts with high >95% d.e.13 Additions of (R)-l-(p-tolysulfinyl)-1,3-8 J.F. Blake D. Lim and W. L. Jorgenson J. Org. Chem. 1994 59 803. 9 A. Kumar J. Org. Chem. 1994 59 230. 10 C. Cativiela A. Avenoza M. Paris J. Org. Chern. 1994 59 7774. 11 K. Fiji K. Tanaka H. Abe K. Matsumoto T. Harayama A. Ikeda T. Taga Y. Miwa,and M. Node J. Org. Chem. 1994 59 2211. 12 B. C. Bezuidenhoudt G. H. Castle J. V. Geden and S.V. Ley Tetrahedron Lett. 1994 35 7451. 13 I. Marko G. R. Evans J.-P. Declerq Tetrahedron 1994,50,4557;I. Marko and G. R. Evans Tetrahedron Lett. 1994 35 2767. C.I. F. Watt butadienes (8) with N-methyl maleimide14 are stereospecific (Scheme 2). Only one endo adduct (9) is formed under thermal or catalytic conditions. With excess NMA the adducts suffer [2,3]-sigmatropic rearrangement yielding enantiometerically pure all-cis cyclohexenols (10). Chiral Catalysts. For Diels-Alder reactions with conventional electron imbalance it is complex formation between dienophile and chiral catalyst that differentiates dienophile faces. Where structural studies of complexes have been undertaken it is clear that no single structural feature of the catalyst or indeed of the reactants can deliver the desired reactivity patterns.Nevertheless transition state models for some catalysed reactions are being developed and it is to be hoped that these will have some predictive power. Enantiomeric excesses of 95% have been achieved in the additions of 2-methoxybutadiene to the C,,-symmetric maleimide (1 l) catalysed by the di-azaluminolidine (12) (Scheme 3). An o-substituent in the dienophile" is essential for high e.e. (95% when R = CH and 62% when R = H). With maleic anhydride completely racemic material is produced. In the catalyst the aryl groups are 3,5-dimethylphenyls and the rn-substituents seem essential for high e.e. The structure of a complex formed between the dienophile (with R = But) and the diazaluminolidine has been deduced from 'H NMR experiments and NOE measurements and a transition state assembly which leads to the observed stereochemistry has been proposed.Scheme 3 Chiral catalysts prepared from scandium or ytterbium trifluoromethanesulfonate (R)-(+)-l,l'-bi-2-naphthol and tertiary amines produce high yields and good diastereo- and enantioselectivities in reactions between cyclopentadiene and acyl- 1,3- oxazolidin-2-ones.'6 The structure of this catalyst has been examined also" and it is believed that the axial chiralty of the binol is transferred via hydrogen bonds to the amines which in turn shield one face of the coordinated dienophile. Stable chiral (acy1oxy)boranes can be prepared by mixing a hindered monoester of tartaric acid with arylboronic acids.' These catalyse hetero-Diels-Alder reactions of l4 E.Arce C. Carreno M. B. Cid and J. L. G. Ruano J. Org. Chem. 1994 59 3421. E.J. Corey S. Sarsher and D.-H. Lee J. Am. Chem. SOC. 1994 116 12089. l6 S. Kobayahsi M. Araki and I. Hachiya J. Org. Chem. 1994 59 3758. l7 S. Kobayashi H. Ishitani M. Araki and I. Hachiya Tetrahedron Lett. 1994 35 6325. Is Q. Gao K. Ishihara T. Maruyama M. Mouri and H. Yamato Tetrahedron 1994 50 979. Reaction Mechanisms -Part (i) Pericyclic Reactions 55 Danishefsky dienes with carbonyl compounds to provide dihydropyrones in high optical purities. A chiral amino-alcohol-derived boron complex similarly catalyses additions of glyoxalate in high enantioselectivity and cis (endo) diastereoselectivity. Chiral bidentate Lewis acids based on 1,8-naphthalenediylbis(dichloroborane)and chiral amino acids or diols show some promise as catalysts of enantioselective Diels-Alder reactions.,' Chiral catalysts for cycloadditions with inverse electron demand have also been described.Silica gel effectively catalyses addition of the electron deficient 3-methoxycarbonyl-2-pyrone to butyl or benzyl vinyl ether to yield bicyclic adducts and titanium(rv) based Lewis acid catalysts incorporating either a tartrate based ligand,2 or more effectively a binol ligand, yield single product diastereoisomers in modest to excellent e.e. The combination of Yb(OTf) and binol described by Kobayashi et a!. also gives good e.e.s for addition of 3-methyloxycarbonyl-2-pyronewith both vinyl ethers and vinyl sulfides.23 The use of these chiral catalysts is not restricted to [4 + 21 cycloadditions.A C,-symmetric bis-sulfonamide-trialkyl aluminium complex for example catalyses asymmetric [2 + 21 addition of ketene with aldehydes affording optically active 4-substituted oxetan-2-ones with up to 74% e.e.,24 and the carbonyl ene reaction of methyl glyoxalate with trisubstituted alkenes can be catalysed by chiral titanium complexes derived from 6,6'-dibromobinol and diisopropoxytitanium dihalide~.~~ Syn-Diastereoisomers are produced with an e.e. of between 60 and 90%. Asymmetric cycloadditions of nitrones to ketene acetals is catalysed by chiral oxazaborolidines derived from N-tosyl-L-a-aminoacids. Best selectivities (e.e. <74%) were achieved with tyrosine-(OBzl) derived catalysts and a working model of the catalyst has been developed.26 Various Dienes and Dienophi1es.-Dienes.In contrast to the behaviour of isodicyc- lopentadiene (13) the dienes (14) (1 5) and (16) all show a preference for reaction from the top face additions to reactive dienophiles. The pattern of selectivities cannot be rationalized in terms of steric effects alone and is taken as a demonstration that the behaviour of isodicyclopentadiene arises from orbital tilting at the diene termini which can overcome steric effects such as torsional strain along the developing bonds.27 Dienes (17) and (18) incorporating the 7-oxabicycloC2.2. llheptenones and their ethylene ketals react with electron-deficient alkynes and sulfur dioxide with high selectivity for the less hindered exo face of the bicycle.28 With N-phenylmaleimide two adducts were formed differing in stereochemistry at the dienophile but both of which were the result of exo attack on the diene.With unsymmetrical alkenes regioselectivi- ties were low. Cyclodimerizations of the dienes were also highly stereo~elective.~~ l9 Y. Motoyama and K. Mikami J. Chem. Soc. Chem. Commun. 1994 1563. 2o M. Reilly and T. Oh Tetrahedron Lett. 1994 35,7209. 21 G.H. Posner J.-C. Carry J. K. Lee D. S. Bull and H. Dai Tetrahedron Lett. 1994 35 1321. 22 G.H. Posner F. Eydoux J. K. Lee and D. S. Bull Tetrahedron Lett. 1994 35,7541. 23 I. Marko and G.R. Evans Tetrahedron Lett. 1994 35 2771. 24 Y. Tamai H. Yoshiwara M. Someya J. Fukumoto and S.Miyano J. Chem. Soc. Chem. Commun. 1994 228 1. 25 M. Terada Y. Motayama and K. Mikami Tetrahedron Lett. 1994 35 6693. 26 J.-P.G. Sneerden A. W. A. Scholte op Reimer and H. W. Scheeren Tetrahedron Lett. 1994 35 4419. 27 E. R. Hickey and L. A. Paquette Tetrahedron Lett. 1994 35 2309 and 2313. 28 L. Meerpool M.-M. Vrahmi B. Deguin and P. Vogel Heh. Chim. Acta 1994 77 869. 29 L. MeerpooI M.-M. Vrahmi J. Ancerewicz and P. Vogel Tetrahedron Lett. 1994 35,11 1. C.I. F. Watt (13) Despite its electron-deficient nature l-(buta-1,3-dien-2-yl)pyridiniumbromide enters into Diels-Alder reaction3' with a range of electron-deficient alkenes and norborene. It is more reactive than isoprene and with unsymmetrical alkenes reactions show the usual para regioselectivity.The ortho-quinomethide (19) generated in situ in refluxing toluene [Scheme 4(a)] reacts in Diels-Alder fashion with both C70 and C,,.31 Three of four possible C, monoadducts and one C, monoadduct were isolated. The adducts were characterized by a combination of NMR spectroscopic methods and shown to have been formed by selective reaction at the poles of the fullerene where there is high local curvature. Additions at the equator were not observed. Benzocyclobutenol or its methyl ether react with C,,in refluxing toluene presumably via their quinine methide forms to give 1 ,g-dihydrofullerene add~cts.~~Furan-based o-quinodimethanes (20)dimerize readily affording high yields of [4 + 41 cycloadduct [Scheme 4(b)].33 Rates are only slightly retarded by alkyl substitution at the 5-position (kH/kButx 4),and it is suggested that this is consistent with a two-step cyclization via an initially formed biradical.Synthesis of an enediyne unit which occurs in many DNA-cleaving antibiotics has been achieved34 by Diels-Alder reaction of 3,4-bis(methylene)- 1,Shexadiyne (21) and reactive dienophiles including maleic anhydride (Scheme 5). With benzoquinone a bis-adduct was formed. Styrene and styrenes carrying alkoxy or thioalkyl a substitu-ents will react with benzoquinone to give modest yields of 1,4-~henanthrenediones.~' 3,5-di-t-butyl-o-quinone behaves as a heterodiene in additions with a range of acyclic dienes yielding vinyl- 1,4-benzodioxines. 36 According to calculations at the MP4SDQ/6-3 lG*//MP2/6-3 lG* level cycloaddi- tion of ethyne and 1H- 2H- and 3H-phosphole all proceed through the concerted [4 + 2) mechanism with quite synchronous bond changes.37 Calculated activation 30 S.-J.Lee C.-J. Chien C.-J. Peng and T.S. Chou J. Org. Chem. 1994 59 4367. 31 A. Herrmann F. Diederich C. Thilgen H.-U. ter Meer and W. H. Muller,Helu. Chim.Acta 1994,77,1689. 32 X. Zhang and C. S. Foote J. Org. Chem. 1994 59 5235. 33 W.S. Trahnovsky C.-H. Chou and T. Cassidy J. Org. Chem. 1994 59 2613. 34 H. Hopf and M. Theurig Angew. Chem. Int. Ed. Engl. 1994 33 1099. 35 N. D. Willmore D.A. Hoic and T.J. Katz J. Org. Chem. 1994 59 1889. 36 V. Nair and S. Kumar J. Chem. SOC.,Chem. Commun. 1994 1341. 37 S.M. Bachrach J. Org. Chem. 1994 59 5027. Reaction Mechanisms -Part (i) Pericyclic Reactions (20) R = H Me But Scheme 4 (21) Bu or SiMe3 Scheme 5 energies of 30.62 17.93 and 28.14 kcal mol- respectively support an earlier sugges- tion that other phospholes undergo rearrangement to the 2H isomer before participa- ting in cycloaddition.Dieneophiles. Cyclopropenone reacts with 1,3-diphenylisobenzofuran (Scheme 6) X-ray crystallography has confirmed that the sole observable Diels-Alder adduct (22) has the exo config~ration.~~ This was expected to equilibrate with its endo isomer (23) whose absence has been rationalized in terms of relative stabilization of the exo adduct by an attractive etherxarbonyl interaction. In the crystal structure r(O. . * C) = 2.54 A and the carbonyl is distinctly pyramidal with the carbonyl carbon displaced by 0.035 A from the plane of its ligands towards the ethereal oxygen.Signals assigned to a transiently formed exo adduct have been observed in NMR monitoring of a reacting mixture of cyclopropenone and 1,3-diphenylisobenzofuran at -30 "C. These rapidly disappear (tl,2 z 1 hour) at -20 "C so that cyclopropenone shows a preference for exo orientation with this particular diene that appears to be kinetic as well as thermodynamic. Diels-Alder reactions of cyclopropenone a~etals~~ have been used in a new tropolone annulation. 2-Azaallenium salts (24) enter into [4 + 21 cycloadditions at low temperature with dienes such as anthracene 1,3-~yclohexadiene or 2-trimethylsilyoxyhexadiene,to yield the cyclic salts (25) with stereoisomeric exocyclic iminium residues [Scheme 38 J.H.Cordes S. De Gala J. Berson J. Am. Chem. SOC.,1994 116 11 161. 39 D.L. Boger and Y. Zhu J. Org. Chem. 1994 59 3453. C.I. F. Watt Ph Ph Scheme 6 7(a)],40 Ene additions compete with cyclization in reactions with dienes in which s-cis conformations are less readily available. With alkenes such as cyclohexene ene addition occurs. Allenes carrying trichlorosulfonyl (26) or sulfinyl substituents are reactive dienophiles and yield Diels-Alder adducts41 with a range of dienes including furan at 70 "C [Scheme 7(b)]. Endo adducts predominate and with y-methylallenyl trichloromethyl sulfone E/Z mixtures are formed. E-vinylboronic esters carrying electron-withdrawing groups at the j-position react with buta- 1,3-diene and 2,3- dimethylbuta- 1,3-diene to give Diels-Alder ad duct^.^^ Ar Ar OTMS X 0 + 'I SO& cI Thiobenzophenone and thiofluorenone are reactive dien~philes~~ with the fluorenone being ca.lo4 times more reactive. Both reactions appear to be concerted 40 A. Geisler and E.-U. Wurthwein Tetrahedron Lett. 1994 35 77. 41 S. Braverman and Z. Lior Tetrahedron Lett. 1994 35 6727. 42 C. Rasset and M. Vaultier Tetrahedron 1994 SO,3397. 43 J. Schatz and J. Sauer Tetrahedron Lett. 1994 35 4767. Reaction Mechanisms -Part (i) Pericyclic Reactions showing only a small solvent dependency and having large and negative entropies of activation. For series of para-substituted benzophenones cycloadditions with 2,3- dimethylbuta-l,3-diene gave a reasonable Hammett correlation with p = 2.4.The reactions of sulfur dioxide behaving as a heterodienophile with buta-l,3-diene and isoprene have been studied at an ab initio leve144*45 Solvent effects are predicted to be important in controlling the exolendo and regiosele~tivities.~~ Intramolecular Diels-Alder Reactions. Intramolecular Diels-Alder reaction of the phenylsulfonyl bearing dienes (27) requires high temperatures (>180"C) and pro- longed reaction times,47 but acceptable yields of hydroindenes and hydronaphthalense (28) are produced. [Scheme 8(a)]. For both chain lengths the bicycles are predomi- nantly trans. The major product of reaction of (29) and (30) by Diels-Alder addition extrusion of sulfur dioxide and intermolecular Diels-Alder addition48 is the all-cis tricyclic ketone (31) [Scheme 8(b)].PhS02q U (27) n =30r4 X =H,SiMe3,PhS (29) (30) Scheme 8 2-Benzopyranones (32) undergo intramolecular cycloadditions with preferred endo addition.49 Rates and cis-stereoselectivities of intramolecular Diels-Alder reactions of trienonenes (33) are enhanced by lithium perchlorate :diethyl ether and camphorsul- fonic acid.50 2 [2 +21 Cycloadditions and Reversions Exposure of crystals of the syn-tricyclo[4.2.0.02~5]octane derivative (34) to X-rays converts it in the solid state into the cis,cis-cycloocta- 1,5-diene derivative (35) without disruption of the crystal structure [Scheme 9(a)].51 44 D. Suarez J. Gonzalez T. L. Sordo and J.A.Sordo J. Org. Chem. 1994 59 8058. 45 D. Suarez T. L. Sordo and J.A. Soedo J. Am. Chem. SOC. 1994 116 763. 46 D. Suarez X. Assfeld J. Gonzalez M. F. Ruiz-Lopez. T. L. Sordo and J. A. Sordo J. Chem. SOC.,Chem. Commun. 1994 1683. 41 S.S.P. Chou C.S. Lee M.-C. Cheng and H.-P. Tai J. Org. Chem. 1994 59 2010. 48 J. D. Winkler S. Kim K. R. Condroski A. Asensio and K.N. Houk J. Org. Chem. 1994 59 6879. 49 E. J. Bush D. W. Jones and F. M. Nongrum J. Chem. SOC. Chem. Commun. 1994 2145. 50 P.A. Grieco S.T. Handy and J. P. Beck Tetrahedron Lett. 1994 35 2663; P.A. Grieco J. P. Beck S. Handy N. Saito and J. F. Daeuble Tetrahedron Lett. 1994 35 6783. 51 A. Mori N. Kato H. Takeshita Y. Kurahashi and M. Ito J. Chem. SOC.,Chem. Comrnun. 1994 869.C.I. F. Watt 0 \ \o (33)n = 1 or2 R=HorMe K R2 0 K 150 "C ox R2FE I R' R' (36)R = H Me But (37) (38) Scheme 9 Ab initio calculations (/6-3 lG*//HF/6-3 1G*)show that the cycloaddition of ketenes and carbonyl compounds52 is both concerted and synchronous. With mono-substituted ketenes exo transition states are preferred. With a Lewis acid catalyst bonding changes are no longer synchronous and the catalyst is also exo with respect to the ring. A level of theory with configuration interaction is required to reproduce the observed regio- and stereoselectivities in calculation of the cycloaddition between methoxyketene and a conjugated imine.53 On heating the readily available methylenecyclopropanes (36) rearrange to the ketene acetals (37) which yield [2 + 21 cycloadducts with range of electron deficient alkenes [Scheme 9(b)].54 The adducts are hydrolytically unstable with cleavage of the four-membered ring occurring readily at the masked b-ketoester bond.With maleate both cis-and trans-cyclobutane dicarboxylates (38) are formed indicating a stepwise process for their formation. The ketene acetals also react with C,* providing another useful route to substituted fullerenes. *' B. Lecea A. Arrieta G. Roa J. M. Ugalde and F. P. Cossio J. Am. Chem. SOC. 1994 116 9613. 53 I. Arrastia A. Arrieta J. M. Ugalde F. P. Cossio and B. Lecea Tetrahedron Lett. 1994 35 7825. 54 S. Yamago A. Takeuchi and E. Nakamura J. Am. Chem. Soc. 1994 116 1123. Reaction Mechanisms -Part (i) Pericyclic Reactions 1,l-Dicyano-2,2-bistrifluoromethylethylene55 is an alkene comparable to TCNE in its electron deficiency and like TCNE reacts with conjugated dienes to yield both [4 + 21 and [2 + 21 adducts.Dichloroneopentylsilene reacts with 1,4-~ycloheptadiene to yield a mixture of [2 + 21 and [4 + 21 addition products.56 With cyclohepta-1,3,5- triene mixtures are again formed but of [2 + 21 and [6 + 21 adducts neither of which can arise by thermally allowed pathways. The [2 + 21 adducts are not stable but rearrange on heating to exo- and endo-silabicyclo[4.2. llnonadienes (39) presumably uia the indicated dipolar intermediate which links all the products (Scheme 10). Photolysis of hexa-t-butyltrisilene produces both di-t-butylsilene and tetra-t-butyl- disilene.The former reacts with alkenes and dienes by insertion yielding siliranes. The latter yields [4 + 21 adducts with dienes but a [2 + 21 adduct has been found in reaction with o-methyl~tyrene.~~ Cl + Scheme 10 3 Cheleotropic Reactions The term 'coarctate' has been coined to describe reactions in which two or more bonds at a single centre are made or broken at the same time.58 Examples include insertions or extrusions of carbenes. These are notoriously difficult to analyse in terms of the familiar topological probes for transition state aromaticity but these have now been extensively reviewed and an appropriate model described. Phenylacetoxycarbene generated by diazirine phot~lysis,~~ shows reactivity similar to phenylmethoxycarbene and phenylchlorocarbene in additions to electrophilic alkenes.However (phenoxymethy1)acetoxycarbene yields the hydride shift product cis-l-acetoxy-2-phenoxyethene, while (phenoxymethy1)methoxycarbene yields none of the corresponding product. Singlet t-butylchlorocarbene generated at low tempera- ture by photolysis of t-butylchlorodiazirine in an N,matrix decays by carbene insertion into a C-H bond at 11K.60 Temperature dependence of rates of this 55 R. Bruckner and R. Huisgen Tetrahedron Lett. 1994 35 3285. 56 W. Ziche C. Seidenschwarz N. Auner E. Herdtwick,and N. Sewald Angew. Chem. Int. Ed. Engl. 1994,33 71. 57 M. Weidenbruch E. Kroke H. Marsmann S. Pohl and W. Saak J. Chem. SOC.,Chem. Commun. 1994 1233. 58 R. Herger Angew.Chem. Int. Ed. Engl. 1994 33 245. 59 R.A. Moss S. Xue and W. Liu J. Am. Chem. SOC. 1994 116 1582. 60 P.S. Zuev and R.S. Sheridan J. Am. Chem. SOC.,1994 116,4123. C.I.F. Watt (43) (41) X = CH2,0,CH=CH or CH2CH2 Me0 (46) (47) Scheme 11 insertion yield curved Arrhenius plots and deuterium isotope effects are large with apparent complete inhibition of reaction at the lowest temperatures. Quantum mechanical tunnelling is suggested to account for the observations. Sulfur dioxide adds slowly (8 days at 25 "C) in homocheleotropic fashion61 to 3,3-dimethylpenta-l,4-diene to yield the bicyclic sulfone (40)[Scheme 11(a)]. Rates are only weakly sensitive to the presence of acid catalysts and unaffected by added radical scavengers.With the bicyclic dienes (41) homocheleotropic addition yielding sulfones (42) competes with cheleotropic addition yielding the sulfolenes (43) which can add a second equivalent of sulfur dioxide [Scheme ll(b)]. In all cases the sulfolenes are the thermodynamic products but the nature of the bridge X has a marked effect on rates and equilibria. Thus when X = CH, homocheleotropic addition is favoured and the sulfolane is formed at -20 "C.At higher temperatures the sulfolene is formed. With X = (CH=CH) the modes compete kinetically. When X = 0 or CH,CH, only sulfolene formation is observed. J.-M. Roulet B. Deguin and P. Vogel J. Am. Chem. SOC.,1994 116 3639. Reaction Mechanisms -Part (i) Pericyclic Reactions Thermolysis of dimethyl- 1,3,4-0xadiazolines affords an entry to carbenes and thermolysis of the butynyloxymethoxyoxadiazoline (44) affords a tricycle array (45) whose formation can be rationalized by a cascade of carbene and other reactions [(Scheme 11 (c)] .62 Thermolysis of spiro-fused p-lactam oxadiazolines (46) appears to yield P-lactam-4-ylidines (47) which can cyclopropanate alkenes [Scheme 11 (d)] .63 Experiments with maleate or fumarate show that the additions are stereospecifically cis with respect to the alkene component.4 1,3-Dipolar Cycloadditions 0xyallyl.-Debromination of cis-1,Sdibromo-1,5-dimethylcyclopentanone can be carried out at low temperature in aprotic solvents using [Cr(CO),NO]- as its (PPh3)N+ salt (Scheme 12).64 Even at -120 "C the expected 2,5-dimethylcyclo- pentyloxyallyl was not observable by NMR spectroscopy.Dimers are formed with the major product being the cis-dioxane compound (48) which has only one of four connectivity patterns possible from union of two oxyallyl units. This compound is thermally labile yielding the isomers (49) and (50). 0 \I Diazoa1kanes.-The reaction of diazomethane with allene has been reexamined and found to be regioselective rather than regiospecific as earlier work had indicated. The regioisomers 4-methylene- 1 -pyrazoline and 3-methylene- 1 -pyrazoline are formed in 93 :7 ratio at 25 0C.65 The new experimental data can be reproduced qualitatively at least by high level ab initio theory but not by semiempirical methods nor indeed by small basis set ab initio methods.Cycloreversion and nitrogen extrusion are competing thermal reactions in the decomposition of the 1-pyrazoline (51) (Scheme 13). Rates and product ratios are only weakly solvent dependent but the cycloreversion is more sensitive than the nitrogen 62 K. Kassam and J. Warkentin J. Org. Chem. 1994 59 5071. 63 M. Zoghbi S.E. Horne J. Warkentin J. Org. Chem. 1994 59 4090. 64 A. P. Master M. Parvez T.S. Sorensen and F. Sun J. Am. Chem. SOC. 1994 116 2804. 65 A. Rastello M. Bagatti and R. Gandolfi Tetrahedron 1994 50 5561. C.Z.F. Watt 0 Scheme 13 extrusion. Non-polar solvents give higher reactivity and larger amounts of cyclorever- sion. Nitrones and Nitrile Oxides.-The homoadamantane incorporated nitrone (52) shows unusual reactivity in adding to nitrileP to give A4-1,2,4-0xadiazoline derivatives albeit under high temperature and with long reaction times [Scheme 14(a)].With acrylonitrile a 55:45 mixture of C=C and C-N cycloadducts is formed. This reactivity pattern is probably evident with this particular compound only because competing modes of nitrone decomposition are blocked by the adamantyl framework. N-alkylhydroxylamines can be formed from ‘normal’ nitrones under cycloaddition conditions and some unexpected losses in stereoselectivity in cycloadditions have now been shown to arise from interconversion of dipolarophiles such as dimethyl maleate and dimethyl fumarate induced by small amounts of such corn pound^.^^ In toluene solvent the additions of C-methyl-N-phenylnitrone (53)with substituted styrenes yields adducts (54) in which cis/trans ratios are all ca.65 :35 except when there is an o-hydroxyl group in the dipolarophile [Scheme 14(b)].68 Then only the cis isomer is produced showing the importance of the hydrogen bonding in the TS. (53) (54) Scheme 14 66 Y. Yu M. Ohno and S. Eguchi J. Chem. SOC.,Chem. Commun. 1994 331. 67 H.G. Aurich G. Frenzen and M.G. Rohr Tetrahedron 1994 50 7417. U. Chiacchio F. Casuscelli A. Corsaro A. Rescfina G. Romeo and N. Uccella Tetrahedron 1994 50 667 1. Reaction Mechanisms -Part (i) Pericyclic Reactions 1,3-Dipolar cycloadditions of pyrazol-4-one-N,N-dioxides (55) show a kinetic preference for formation of exo adducts with wide range of alkenes (Scheme 15).69 With polar asymmetrically substituted alkenes the observed orientations of addition are in agreement with the predictions of perturbation theory with bonding of the oxygen of the nitrone and C of the alkene occurring where the coefficient of the interacting frontier is largest.Acrylonitrile oxide has been generated in situ by dehydration of 1-nitropropene and adds as a 1,3-dipole to norbornene to yield both exo and endo 2-isoxazoline adducts in 3 :1 ratio7' in only moderate overall yield. (55) (a) R' = R2= C02Me (b) R' = Me; R2= C02Me Scheme 15 Others.-The pyrroles (56) and (57) are formed in a 54 :47 ratio from 1,3-dipolar addition of the isotopically labelled munchones (58)with methyl pr~piolate,~' showing that there is little inherent electronic imbalance between their carbon termini (Scheme 16).Regioselectivities in a reaction with a series of arylthio alkyl and phenyl substituted munchones are also reported and selectivities are only greater than 80% when one or other of the reacting carbons carries hydrogen. The contributions of frontier interactions to the selectivities seems to be minimal. (58)(a) R' = CH3 R2= CH3 (b) R' = 13CH3 R2 = CH3 (57) Scheme 16 5 [3,3] Sigmatropic Shifts These remain by far the commonest of molecular rearrangements. Both Cope and Claisen processes are used in many guises in important synthetic reactions. Detailed descriptions of transition state geometries and bonding arrangements therein continue to challenge experimentalists and theoreticians. 69 M.Eto Y. Yoshitake K. Harano and T. Hisano J. Chem. SOC.,Perkin Trans. 2 1994 1337. 'O P.W. Ambler R. M. Paton and J. M. Tout J. Chem. SOC.,Chem. Commun. 1994 2661. " B. P. Coppola M.C. Noe D.J. Schwarz R. L. Abdon and B. M. Trost Tetrahedron 1994 50 93. C.I. F. Watt Cope Rearrangements.-CASSCF-MP2 calculations on the Cope rearrangement using large basis sets predict a single aromatic transition A semiempirical of the Cope rearrangement of singly annelated semibulvalenes (59) with n = 2-5 (Scheme 17) yields qualitatively similar results with MNDO AM1 and PM3 methods. Trends if not absolute values in available experimental rate and equilibrium measurements were reproduced. When n = 2 the ground state of the molecule is predicted to be a symmetrical homoaromatic species (60).Scheme 17 Von Doering et a/. have determined activation parameters (AH* = 29.9 kcal mol- ' and AS = -15.0e.u.) for Cope rearrangement of [6-'3C]-(E)-1,4-diphenylhexadiene (Scheme 18).74 In this compound (61) phenyls are at active positions in any allyl radical formed by C-3-C-4 homolysis (62) yet the parameters and a negative activation volume (AV* = -13.4cm3 mol-') point to ring formation in the transi- tion state. These should be compared with AH* = 21.2 kcal mol- ' and AS* = -20.8 e.u. for rearrangement of 2,5-diphenylhexa-1,5-diene(63) where the phenyl groups would be at the nodal position of an allyl radical. The relative reactivities are more consistent with reaction with initial C-1-C-6 formation via a cyclohexa-l,4-diyl radical (64).New measurements of rates and equilibria for the cis-trans isomerism of 1,l'-bi-3-phenylcyclohex-2-enylidenes provide an estimate of the stabilization in the cinnamyl radical and thermochemical analysis of these reactions and other phenyl substituted hexadienes is presented. Relative to the appropriate non-interacting diphenylcyclohexa- 1,4-diyl radicals (65) estimated ener- gies of concert are 15.9 and Okcalmol-' respectively for the isomeric diphenyl- hexadienes. Other molecules with structural features which might promote a stepwise Cope in rearrangement by a cyclohexane- 1,4-diyl intermediate include octa- 1,2,6-triene~,~ which one of the radical centres would be allylic and an estimate using Benson's group increments suggest that the biradical could lie as much as 17.6 kcal mol- ' below a concerted transition state.Pyrolysis of (E)-5-methylocta-l,2,6-triene(66) yields (E)-4-methyl-3-methylene-1,5-heptadiene (67)(Scheme 19) with activation parameters AH+ = 30.9kcalmol-' and AS* = -12.7eu. With optically active material the rearrangement occurs with 68 % retention of enantiomeric purity corresponding to a 72 D.A. Hrovat K. Morokuma and W.T. Borden J. Am. Chem. SOC. 1994 116 1072. 73 T.V. Williams and H.A. Kurz J. Chem. SOC.,Perkin Trans. 2 1994 147. 74 W. von E. Doering L. Birladeanu K. Sarma J. H. Teles F.-G.Klarner and J.-S. Gehrke J. Am. Chem. SOC. 1994 115 4289. 75 T. A. Wessel and J. A. Berson J. Am. Chem. SOC. 1994 116 493. Reaction Mechanisms -Part (i) Pericyclic Reactions R or (a) R = H and R’ = Ph (b) R = Ph and R’= H R R (64) (62) Scheme 18 15.5% contribution that is antarafacial with respect to the ally1 subunit.The simplest explanation of this result is that the anticipated diversion from a concerted to a two-step pathway has occurred with a conformationally mobile biradical intermedi- ate. Scheme 19 Anionic oxy-Cope rearrangement of (R)-(E)-1-phenylhexa- 1,5-dien-3-01 (68) yields the rearrangement product (69) with 30% e.e.76 [Scheme 20(a)]. This result and similar ones with other simple substrates suggest a preference for the anionic oxygen to adopt the pseudo-axial orientation on the chair-like transition state. The preference however is clearly not strong and it is easily overcome by additional steric constraints in more highly substituted arrays.l6 E. Lee Y. R. Lee B. Moon 0.Kwon M.S. Shim and J.S. Yun J. Org. Chern. 1994 59 1444. C.I.F. Watt Cope rearrangements which usually require T > 200 "C in acyclic 1,5-diynes occur readily in cycloocta-l,5-diynes.77 Thus the bicyclic alcohol (70) yields the bis-allene (71)with tl,* z 6.4hrs at 50 "C [Scheme 20(b)]. Absence of the exocyclic double bond renders the rearrangement faster yet. 0- OH Ph Scheme 20 Claisen Rearrangements.-Transition states have been located and kinetic isotope effects calculated for the prototype Claisen rearrangement7' of ally1 vinyl ether. There are significant discrepancies between experimental and RHF/6-3 lG* and MP2/6-3 lG* calculated values.Complete active space CASSCF calculation using the 6-31* basis set gives a single transition structure with more bond breaking and the calculated heavy atom effects are in better agreement with experiment. Bond orders of 0.31 (C-0) and 0.18 (C-C) are found using the modified Pauling bond order relationship compared with estimates from experiment of 0.33 and 0.17 respectively. Transition states energetics and kinetic isotope effects in both Cope and Claisen rearrangements have also been calculated using density functional theoretical methods.79 Non-local spin density approximations are necessary for good agreement between experimental and calculated activation energies. These DFT methods then provide descriptions of transition state geometries and associated kinetic isotope effects for comparison with experiment which are on a par with correlated MO theory.Two independent high level MO studies of the conversion of chorismic acid into prephenic acid have been reported."." These predict a loose transition state with appreciably elongated breaking C-0 bonds and a long developing C-C bond in contrast to the results of 77 K. Iiada and M. Hirama J. Am. Chem. SOC. 1994 116 10310. '' H.Y. Yo0 and K.N. Houk J. Am. Chem. SOC. 1994 116 12047. 79 0.Weist K. A. Black and K.N. Houk J. Am. Chem. SOC. 1994 116 10336. 0. Weist and K.N. Houk J. Org. Chem. 1994 59 7582. M. M. Davidson and I. Hillier J. Chem. SOC. Perkin Trans. 2 1994 1415. Reaction Mechanisms -Part (i) Pericyclic Reactions semiempirical methods.Comparisons with allyl ether suggest that rate enhancements in the chorismate rearrangement follow from both ground state destabilization and transition state stabilization involving electron delocalization into the ring. (72) X = OTMS or COOMe (74) Scheme 21 I4C kinetic isotope effects have been measuredg2 for the C-1 C-2 C-4 and C-6 positions in the rearrangements of 2-(trimethylsily1oxy)- and 2-(methoxycarbonyl)-3- oxahexa-1,5-dienes (72) [Scheme 21(a)]. The data together with earlier C-4 and C-6 dueterium isotope effects were fitted to transition structure models using the Bebovib method. The only models yielding reasonable fits agree that bond breaking at C-4 is greater than 70% while bond making is less than 20%.If a recent suggestion that conversion of an alkene radical into an allyl radical loosens C-N bending motions is incorporated then the imbalance between bond breaking is reduced but not eliminated. In the Claisen rearrangements of the 5-substituted adamantylidene compounds (73) and (74) the new bonds are formed mainly at the alkene face syn to the 5-substituent (1.33 < syn/anti < 1.56) [Scheme 21(b)].g3 Replacement of hydrogen by phenyl or oxyanion at the alkylidene terminus in the latter does not alter the preference. These and related oxy-cope and allyl vinyl sulfoxide rearrangements show a remarkably 82 L. Kupczyk-Subotkowska W. H. Saunders H. J. Shine and W. Subotkowska J.Am. Chem. SOC.,1994,116 7089. 83 A. Mukherjee Q.Wu and W. J. le Noble J. Org. Chem. 1994 59 3270. C.I.F. Watt constant face selectivity. It is suggested that newly forming bonds are always electron deficient and stabilized through hyperconjugation with antiperiplanar vicinal bonds. The isomeric aryl4,6-di-O-acetyl-dideoxy-~-erythro-hex-2-ene pyranosides (75) and (76)rearrange at 170 "C to the expected Claisen products (Scheme 22).84 Surprisingly the a-anomer in which the migrating group is expected to be quasi-axial is ca. 100 times less reactive than its anomer. AM calculations and 'H NMR coupling constants however showed that both anomers adopted conformations with axial aryloxy groups. The optimized transition state for the rearrangement of the a-anomer has a chair form for the reacting atoms and for the unsaturated sugar moiety.For the p-anomer the sigmatropic unit again adopts a chair but the sugar moiety adopts the ring B form. Both can benefit from anomeric stabilization. & rrn = 35hours * ' O R (75) &-o-.-AcO D rlR = 0.5 hours R \ AcO8-0 OH AcO (76) AcO Scheme 22 The Claisen rearrangement of aryl allenylmethyl ethers (77) to 2-(o-hy-droxyary1)buta- 1,3-dienes cannot be induced thermally nor are they catalysed by protic acids [Scheme 23(a)]. However with tris(4-bromopheny1)aminiumin acetonit- rile [3,3] shifts occur at room temperature in the first example of a cation radical induced Claisen reaction.85 The thio-Claisen reaction is poorly characterized compared to its oxygen analogue but has been put to good synthetic use as the basis of a stereocontrolled construction of vicinal tertiary centres.86 Semiempirical calculations (MNDO) on the 3-aza-Claisen rearrangement favour reaction via a spin paired chair transition state and predict enhanced rates for a variant with the nitrogen carrying an anionic s~bstituent.~~ The y,h-unsaturated nitrile (78) equilibrates at room temperature with the N-allylketene (79) [Scheme 23(b)].88 Neither rates nor equilibrium compositions (ca.50 50) are strongly dependent of solvent and experiments with isotopically labelled material 84 K. K. Balasubramanian N. G. Ramesh A. Pramink and J. Chandrasekar J. Chem. SOC.,Perkin Trans. 2 1994 1399. 85 S. Dhanalekshimi C.S. Venkatachalam and K. K. Balasubramanian,J. Chem.SOC.,Chem.Commun. 1994 511. 86 P.N. Devine and A. I. Meyers J. Am. Chem. SOC.,1994 116 2633. J.C. Gilbert and K.R. Cousins Tetrahedron 1994 50 10671. R. Bruckner and R. Huisgen Tetrahedron Lett. 1994 35 3281. Reaction Mechanisms -Part (i) Pericyclic Reactions +* R’ --2R* 3R (77) NC !$:F3 (78) (79) Scheme 23 excludes dissociative pathways. The reaction is best described as a 3-aza Claisen rearrangement. 6 [1,3] Shifts The stereochemical requirements for concerted and allowed [1,3] shifts are usually sufficiently demanding that non-concerted pathways compete and often are followed exclusively. Nevertheless because pathways are competitive rearrangements of this type remain a valuable testing ground for the limits of pericyclic processes.Vinylcyclopropane Rearrangements.-The thermal isomerization of vinylcyclo-pro- pane to cy~lopentene~~ has been investigated using specifically deuteriated precursors syn-(E)- and syn-(Z)-2,3,2’-d3-vinylcyclopentene(80). At 300 “C k = 3.4 x s-’ the resultant three stereoisomeric 3,4,5-d3-cyclopentenes [Scheme 24(a)] have been identified and quantified by NMR to allow extraction of relative rates for the four stereochemically distinct combinations of supracacial and antarafacial at the ally1 array and of retention and inversion at the migrating carbon in the 1,3-migration. These are kSi = 4070 k, = 23% kai = 13% and k, = 2470 so that there is no significant kinetic preference for the formally allowed si and ar pathways and diradical intermediates seem obligatory.(1 R,2S)-trans-l-[(E)-l -propenyl]-2-phenylcyclop-ropane is reversibly equilibrated with its enantiomer and with enantiomers of cis-1-[ (E)-1-propenyl]-2-phenylcyclopropane.Isomers of 3-methyl-4-phenylcyclopen-tene form more slowly and kinetic and stereochemical measurements again show that all four distinct reaction pathways occur.9o Relative contributions are remarkably close to those found in the absence of the phenyl substituent and it seems that stereochemistry in these rearrangements has little to do with orbital symmetry or mass or the radical stabilizing abilities of substituents. The diphenylethenylidenecyclopropanes (81) rearrange thermally to 89 J. E. Baldwin K.A. Villarica D. I. Freedberg and F.A. L. Anet J. Am. Chem. SOC. 1994 116 10845 J. E. Baldwin and S. Bonacorsi J. Org. Chern. 1994 59 7401. c.I. F. Watt diphenylethenylidenylcyclopentenes(82) between lo2 and lo3 faster than vinylcyclo- propanes [Scheme 24(b)].9' With a stereochemically defined substrate for R3 = R4= Me and R' = R2 = H a mixture of cis and trans-3,5-dimethylcyclopen-tenes was formed. Reaction via a biradical intermediate rather than by 1,3-sigmatropic shift seems likely. Flash vacuum thermolysis of N-acyl cyclopropyl imines carrying phenyl or phenacyl substituents at C-1 or C-2 of the cyclopropane has yielded 2-p~rrolines.~~ Without these substituents only polymeric products were obtained. Vinylcyclobutane Rearrangements.-Rearrangements of 2-vinylcyclobutanol (83) to 3-cyclohexanolg3 are base catalysed (Scheme 25) proceeding via an anionically accelerated 1,3-shift and first order rate constants for the potassium salt in THF vary inversely with salt concentration suggesting that ion pair dissociation precedes rearrangement.The Z isomer epimerizes to the E isomer 36 times faster than the E isomer yields the ring-opened product. Secondary deuterium isotope effects are kHz/kD2= 1.34 at the vinyl terminal and k,/kD = 1.12 at the carbinol position and are consistent with an allyl anion/aldehyde intermediate (84). RHF ab initio computa-tional studies on sodium 2-vinylcyclobutoxide using a 3-21G basis set found four distinct energy minima corresponding to allyl anion/aldehyde species with oxygen coordinated metal ion two with trans,and two with cis geometries at the allyl residue.Bicyclic Arrays.-Thermolysis of 7,7-dimethylbicyc10[3.2.O]hept-2-ene~~at 275 "C yields none of the 1,3-carbon shifted product. Instead over 84% of reaction is fragmentation to cyclopentadiene and isobutylene. Of the remaining l6% the bulk could arise by a 1,5-hydrogen shift from the endo methyl to C-3.Reaction is one order of magnitude slower than in 2,2-dimethylvinylcyclobutane. 91 K. Mixuno H. Sugita T. Kamada and Y. Otsuji Chem. Letters 1994 449. " P.L. Wu and W. S. Wang J. Org. Chem. 1994,59 622. 93 N.J. Harris and J. J. Gajewski J. Am. Chem. SOC. 1994 116 6121. 94 T. E. Glass P. A. Leber and P. L. Sandall Tetrahedron Lett. 1994 35 2675. Reaction Mechanisms -Part (i) PericycIic Reactions (83)R = R2= H R = D; R2 = H R=H;R2=D Scheme 25 7 Electrocyclic Reactions A new route to 1,2-dihydrocyclobutylarenes95uses the double cyclization of ene-diallenes (85) [Scheme 26(a)].When the allenes substituents are phenyl the initially formed bismethylenecyclohexadiene rearranges thermally to the cyclo- butylarene. When the allenes carry terminal t-butyl groups the reaction does not occur. Benzylidenebenzocyclobutenones (86) suffer photoinduced E-2 isomerism [Scheme 26(b)]. A flash photolysis study has established the intermediacy of the ketene-allene (87) which has a lifetime of 26 ns in acetonitrile and can be trapped by water or methanol.96 Initial products of photoisomerization of highly alkylated butadienes (88) which cannot adopt a planar conformation are bicyclo[ 1.1 .O]butanes [Scheme 26(~)].~’ The photoproducts are not stable but rearrange to the cyclobutenes presumably by homolysis of the central bond and hydrogen atom migration.The completely substituted diene with R’ = R2 = methyl also yields the bicyclo[l.l.O]butane as the major product but surprisingly also 25% of the cyclobutene electrocyclic ring closure product. Solvent effect in disrotatory ring openings of cyclopropanone and 2,2-dimethylcy- clopropanone to the isomeric oxyallyls have been calculated by Monte-Carlo simulation^.^^ TS and ground state geometries were obtained by (4/4) CASSCF calculation with a 6-3 1G*basis set and charges determined for use in fluid simulations. The results are in good agreement with available experimental data and support the intermediacy of the oxyallyls in cyclopropanone stereoisomerizations.Transition states are close to the oxyallyls and have diradical rather than dipolar character. Reaction of chlorocarbene and arylchlorocarbenes with 2-vinylpyridine yields 3-substituted indolizine~,’~ by a mechanism believed to involve cyclization of an 9s F. Toda K. Tanaka I. Sano and T. Isozaki Angew. Chem. Int. Ed. Engl. 1994 33 1751. 96 R. Boch J. C. Tradley T. Durst and J.C. Scaiano Tetrahedron Lett. 1994 35 19. 97 H. Hopf H. Lipka and M. Tratteberg Angew. Chem. Int. Ed. Engl. 1994 33 204. 98 D. Lim D. A. Hrovat W. T. Borden and W. L. Jorgensen J. Am. Chem. SOC. 1994 116 3494. R. Bonneau Y. N. Romashin M. T. H.Liu and S. E. MacPherson J. Chem. SOC.,Chem. Commun. 1994 509. C.I.F. Watt 4Ar 'L (88)(a) R' = R~= H (b)R1= H R2= Me (c) R2 = R' = Bu' Scheme 26 initially formed pyridinium ylid and elimination of HC1 from the resulting dihydroin- dolizine. In presence of acid the equilibrating mixture of (89) and (90) cleanly forms a dimer (91) whose structure is confirmed by X-ray crystallography (Scheme 27).'0° 8 Miscellaneous Processes 1,9acyl Migrations.-In methanol solution 5-benzyl-l,2,3,4,5-pentakis(methoxycar-bony1)cyclopentadiene rearranges thermally by 1,5-migration of methoxycarbonyl groups."' Under the same conditions 5-p-methoxybenzyl-l,2,3,4,5-pentakis(methoxycarbony1)cyclopentadiene fragments presumably via an ion pair mechanism yielding 1,2,3,4,5-pentakis(methoxycarbonyl)cyclopentadiene7and p-methoxybenzyl methyl ether.Rearrangements of Vinyl Aziridines.-Optically active vinyl aziridines (92) are quantitatively transformed into allylic imines (93) by heating in refluxing benzene (Scheme 28).' O2 Reactions are stereospecific and product stereochemistries are loo J. B. Press K. L.Sorgi J. J. McNally and G. C. Leo J. Org. Chem. 1994 59 5088. E.A. Jefferson and J. Warkentin J. Org. Chem. 1994 59 463. lo* J. Ahman P. Somfal and D. Tanner J. Chem. SOC. Chem. Commun. 1994 2785. Reaction Mechanisms -Part (i) Pericyclic Reactions Scheme 27 / C02Bu' I Scheme 28 consistent with the indicated transition structure. With LDA an aza-[2,3] Wittig rearrangement occurs yielding only the cis-2,6-substituted tetrahydropyridine (94) and again the stereochemistry is consistent with the depicted transition structure.' O3 Stereoisomeric aziridines in which the vinyl group and alkyl substituent were cis on the cyclopropane gave no allylic imine under thermolysis and the aza-Wittig rearrange- ment yielded almost equal amounts of cis and trans-2,6-disubstituted tetrahydro- pyridine.In this case presumably there is steric interference to the nitrogen inversion which is required to place the participating homodienyl components in the cis arrangement necessary for concerted processes. Ene and Retro-ene Reactions.-Solvent effects in the ene additions of diethyl azodicarboxylate (DEAD) and N-phenyltriazolinedione (NPTAD) to 2-methyl-2-butene have been examined.lo4 In neither case is the dependence large but with DEAD rates seem to be most sensitive to solvent acidity while the reactions of NPTAD are related to solvent nucleophilicity.Excellent correlations are obtained in lo3 J. Ahman and P. Somfai J. Am. Chem. SOC. 1994 116 9781. '04 G. Desimoni G. Faiti P. P. Righetti A. Sfulcini and D. Tsygdnov Tetrahedron 1994 50 1821. C.I.F. Watt X (95) X = H,H 0,CH2 Y = CH2 C=C(CH3)2,C(CH2)2 (96) Y = CH2 or C(CH2)2 Scheme 29 both cases between reactivities of these are enophiles and dienophiles. The thermal decomposition of allylsulfinic acid is formally a retro-ene reaction yielding propene and sulfur dioxide. The activation volume has been found to be negative AV* = -5.5 cm3 mol- ' despite a large positive reaction volume AV* E 20cm3mol-' and is consistent with a fully concerted process as is a substantial deuterium kinetic isotope effect (kH/kD = 2.5 at 97 "C).lo5 Solvent effects are small.Hydrogen Transfer in syn-Sesquinorbornenes-A series of syn-sesquinorbornene disulfones (95) have been prepared and structures determined by X-ray crystallogra- phy.lo6 These rearrange thermally by transfer of the endo-a-sulfonyl hydrogens to the nearby norbornenyl double bond and relative rates at 160 "C have been determined and span a more than lo4 range. Compounds with the central cyclopropane (X = CH,) are most reactive and those in dihydro series (X = H,H) the least. Rates correlate poorly with geometric parameters such as intra-gap distances but it is clear that steric compression is important with non-bonded interactions particularly when X = CH, being transmitted via the 'wings' of the molecules to the hydrogen transfer site.For two of the series (96) with X = CH, singly and doubly deuteriated iso- topolymers have been prepared and primary kinetic isotope effects determined. When Y = C(CH,), kH,/kHD = 2.9 and kHH/k,D = 8.5 at 100"C. The ratios obey the rule of geometric mean and seem consistent with a concerted cZs+ c2s+ 7cZs shift of hydrogens from one site to the other. A computational study of this reaction was able to reproduce the experimental ratios without including tunnelling corrections. When Y = CH, the reaction is ca. lo3times slower and kHH/kHD = 2.1 and kHH/kDD= 11.2.lo5 S. D. Hiscock N.S. Isaacs M. D. King and D. J. Young J. Chem. SOC.,Chem. Commun. 1994 1381. lo' G.A. O'Dougherty R.D. Rogers and L.A. Paquette J. Am. Chem. SOC. 1994 116 10883. Reaction Mechanisms -Part (i) Pericyclic Reactions The rule of geometric mean is clearly not obeyed and furthermore Arrhenius plots give AHHIAH = 0.4 and A,,/A, = 0.004 suggesting the occurrence of quantum mechan- ical tunnelling possibly related to the higher reaction barrier in these compounds. Non-concerted pathways however cannot be excluded. Enediyne Cyc1izations.-Rates have been determined for Bergman cyclization of some simple aromatic enediyneslo7 and are not appreciably different from those of the corresponding acyclic non-aromatic arrays.Rates are however very sensitive to acetylenic terminal substitution; a single alkyl substituent raised the activation energy by 3 kcal mol- and a second by another 6 kcal mol- High level ab initio calculations on the prototype cyclization of hex-3-ene-1 ,5-diynelo8 to the singlet p-benzyne biradical predict a barrier of 25.0 kcal mol- for the cyclization and an enthalpy of reaction of 4.9 kcal mol- ' to be compared with experimental values of 32 and 14 kcal mol -respectively. The discrepancy between calculated and experimental reaction enthalpies is substantial but the experimental measurements assume the additivity of group energy increments and it is suggested that this assumption is not well founded. The calculations do not support Nicolaou's suggestion that the cyclization is initiated in enediyne-based anticancer agents by a compression of the C-3-C-3' distance from 3.6 to 3.2& lo' J.W.Grissom T.L. Calkins H.A. McMillen and Y. Jiang J. Org. Chem. 1994 59 5833. lo* R. Lindh and B.J. Persson J. Am. Chem. SOC. 1994 116 4963.