4 Reaction Mechanisms Part (i) Pericyclic Reactions By D. W. JONES Department of Organic Chemistry The University Leeds LS2 9JT 1 General The two most cited reviews published in Angewandte Chemie (ht. Ed. Engl.) over the twenty-five years of its existence both deal with pericyclic reactions. In first place with 1821 citations comes Woodward and Hoffmann's famous review 'The Conservation of Orbital Symmetry'.'" Huisgen's article '1,3-Dipolar Cycloadditions -Past and Future'lbSC follows with 1449 citations. It is a tribute to Woodward and Hoffmann that not only their theory but the language they invented to describe it have largely survived the test of time. One troublesome point of semantics not discussed by them arises for concerted (one-step) but asynchronous reactions in which at the transition state (TS) not all bond-making and bond-breaking processes have proceeded to the same extent.It has been suggested that the term two-stage be used when some of the changes in bonding take place mainly before the TS and the remainder between the TS and the The description of such TS's as biradicals is inappropriate if there is interaction between the formal radical centres which confers a degree of cyclic conjugation; the term biradicaloid TS is preferable." 2 Cycloaddition Reactions Evidence for the concertedness of the addition of butadiene to ethylene has been obtained by addition of (1) to cis-dideuterioethylene (2) which gives the cis-adduct (3) and less than 1 % of its trans-isomer.2a Since the barrier to rotation in a biradical intermediate (4) would be expected to be only 0-0.4 kcal mol-' extensive loss of stereochemistry would have been expected if (4) were an intermediate.The reverse Diels-Alder reaction of an adduct derived from two aromatic molecules should most closely approach the ideal synchronous reaction.2b In such adducts both addends lack the two singly occupied p-orbitals required for aromaticity and only simultaneous generation of these allows the TS to acquire part of the aromatic ' (a) R. B. Woodward and R. Hoffmann Angew. Chem. Znt. Ed. Engl. 1969 8 781; (6) ibid. 1986 25 A-3; (c) R. Huisgen ibid. 1963 2 565; (d) M. J. Goldstein and J. L. Thayer J. Am. Chem. Soc. 1965 87 1925; (e) M. J. S. Dewar S. Olivella and J. J. P. Stewart ibid.1986 108 5771. '(a) K. N. Houk Y.-T. Lin and F. K. Brown J. Am. Chem. SOC.,1986 108 554; (6) A. Bertsch W. Grimme and G. Reinhardt Angew. Chem. Znt. Ed. Engl. 1986 25 377; (c) R. Engelke J. Am. Chem. SOC.,1986,108,5799; (d) F.-G. Klarner B. M. Dogan 0.Ermer W. von E. Doering and M. P. Cohen Angew. Chem. Znt. Ed. Engl. 1986 25 108; (e) H. D. Roth M. L. M.Schilling and C. J. Abelt J. Am. Chem. Soc. 1986 108 6098; Tetrahedron 1986 42 6157; (f)S. D. Kahn C. F. Pau L. E. Overman and W. J. Hehre J. Am Chem. Soc. 1986 108 7381. 29 D. W. Jones D stabilization. For a series of five adducts made up from two arenes e.g. (5) and (6) the reduction in the TS state energy for cycloreversion was 43% of the resonance energy gained. The activation free-energy for the cycloreversions extended over a range of 13 kcal mol-'.Since rate-determining single bond cleavage to a biradical would result in a variation of only 2kcalmol-' in the resonance energies of the intermediates a synchronous mechanism is indicated. A theoretical study on the other hand predicts an asynchronous mechanism for the formation of (5) from two benzene molecules.2c The thermal dimerization of 1,3-cyclohexadiene gives the endo (7) and em (8) Diels-Alder dimers as well as the syn (9) and anti (lo) (2 + 2)-dimers and the threo (6 + 4) ene product (1 1). The activation volumes and energies for the formation of these products suggest concerted mechanisms for (7) and (11) and two-step mechanisms for (8) (9) and (10). Here the concerted processes are less than 4 kcal mol-' more favourable than the two-step processes.The novel (6 + 4)-ene process (12; arrows) showed a KIE (kH/kD) of 2.42 similar to that found for the normal (4 + 2) ene reaction.2d Spiro[2,4]heptadiene undergoes easy (4 + 2)-dimerization to (13) via photo-chemical electron-transfer to strong electron acceptors. Time-resolved CIDNP effects Reaction Mechanisms -Part (i) Pericyclic Reactions 4 -4 ,+; indicate the radical cation (14) is present during the addition2' so that at least a part of the reaction is two-step. Whilst the FMO model correctly predicts the major regioisomer from the reaction of mono-substituted dienes with mono-substituted dienophiles the theory overesti- mates the directing ability of a 2-substituent on the diene in competition with a 1-substituent.Experimentally even strong donors like alkoxyl at C-2 are dominated by weak donors like methyl at C-1 and if the same group is present at both C-1 and C-2 of the diene it is the C-1 substituent which directs the addition. An alternative approach which partly overcomes this problem uses complementary reactivity sur- faces for the diene and dienophile.2f The electrophilic surface of an electron-poor dienophile and the nucleophilic surface of an electron-rich diene are derived by calculating the interaction of hydride ion and a proton with the respective surfaces; the results are displayed in colour code for matching. It is still not possible to predict accurately which diastereotopic face of a diene will be preferentially involved in a Diels- Alder addition; the undesired arrangement (15)dominated in an approach to actinobolin although related allylically oxygenated dienes had shown the opposite facial ~electivity.~" The solid-state conformation (16) ZHN-/=+ I -SiO+ 7 I ' CHzOAcAcO H H- (15) (a) A.P. Kozikowski T. Konoike and T. R. Nieduzak J. Chem. SOC.,Chem. Commun. 1986 1350; A. P. Kozikowski and T. R. Nieduzak Tetrahedron Lett. 1986 27 819; (b) R. C. Gupta A. M. Z. Slowin R. J. Stoodley and D. J. Williams J. Chem. Soc. Chem. Commun. 1986 1116; (c) S. D. Kahn and W. J. Hehre Tetrahedron Lett. 1986 27 6041; (d) G. H. Posner and D. G. Wettlaufer J. Am. Chem. Soc. 1986 108 7373; Tetrahedron Lett. 1986 27 667; (e) D. L.Boger and M. Patel Tetrahedron Lett. 1986 27 683; (f)T. R. Kelly A. Whiting and N. S. Chandrakumar J. Am. Chem. Soc. 1986 108 3510; K. Maruoka M. Sakurai J. Fujiwara and H. Yamamoto Tetrahedron Lett. 1986,27,4895; (8)S. G. Davies and J. C. Walker J. Chem. SOC.,Chem. Commun. 1986 609; (h) J. W. Herndon J. Org. Chem. 1986 51 285; (i) P. G. Lenhert C. M. Lukehart and L. Sacksteder J. Am. Chem. SOC.,1986 108,793; (j)K. Furuta K. Iwanaga and H. Yamamoto Tetrahedron Lett. 1986 27 4507. D. U? Jones is consistent with an approximately sp2-hybridized 0-1 whose lone pair can both conjugate with the diene system and participate in an exo-anomeric effect with the C-1'-0-1' bond. Diene attack from above upon the cisoid conformer of (16) derived by the 180" bond rotation shown accounts for the useful facial selectivity exhibited by this diene.,' Vinyl sulphoxides add dienes via the cisoid conformer shown in (17).Electron-rich dienes select the face opposite the sulphur lone pair even at the expense of steric clash with a bulky R group.3c The enol ether (18) reacts with the electron-deficient diene (19) with good diastereoface selectivity despite the separ- ation of the stereogenic centre in (18) from the double bond by a freely rotating ether link.," Both butadiene and 1-methoxy-3-trimethylsilyloxybutadiene add exclusively syn to the heteroatom bridge of the olefins (2O).," Diels- Alder additions to naphthoquinones like (21) proceed with high asymmetric induction when conduc- ted in the presence of chiral Lewis acids prepared in sitw31 The (S)-( + )-acryloyl complex (22) adds cyclopentadiene in the presence of zinc chloride to give mainly (23) derived by addition to the face of the double bond away from the PPh ligand.Oxidative removal of the iron (Ce'") gave endo-norbornene-2-carboxylicacid characterized as the optically pure iod~lactone.~~ The related acyl-iron complexes (24; R = Hor Me) add smoothly to dienes at 25 "C under ethylaluminium dichloride catalysis.3h Formulation of the reacting species as (25) agrees with the known dienophilic reactivity of related Fischer carbene complexes like (26) which react 0-A1C1 E t OMe / C' H~C=CH' +cr(co) (a) M. E. Jung and K. R. Buszek Tetrahedron Lett. 1986,27 6165; (b) S. J. Danishefsky and C. Vogel J.Org. Chem. 1986 51 3915;(c) P. A. Grieco S. D. Larson and W. F. Fobore Tetrahedron Lett. 1986 27 1975; (d) P. A. Grieco and S. D. Larsen J. Org. Chem. 1986,51,3553; (e) P. G. Gassman and D. A. Singleton J. Org. Chem. 1986 51 3075; (f)K. Hayakawa S. Ohsuki and K. Kanematsu Tetrahedron Lett. 1986,27,947; K. Hayakawa T. Yasukouchi and K. Kanematsu ibid. 1986,27,1837; (g)R. Sigrist M. Rey and A. S. Dreiding J. Chem. SOC., Chem. Commun. 1986,944. Reaction Mechanisms -Part (i) Pericyclic Reactions with simple dienes ca. lo4 times more rapidly than methyl acrylate with improved regio- and stereo-~electivity.~' For the addition of dimenthyl fumarate to several dienes Et2AlC1 is much superior to AlC13 in the diastereoisomeric excesses ~btained.~' ,Other novel dienophiles include the vinylpyridinium salts (27; Z = CN CO,Me H) which react with cyclopentadiene in MeOH-H,O to give exclusively the adducts (28) with endo-pyridinium and the imine (29) which reacts with (30) (BF,.Et,O catalyst) as a key step in the synthesis of ipalbidine!b Iminium salts derived from a number of a-dicarbonyl compounds e.g.(31) react with cyclo- pentadiene in water at 25°C to give good yields of adducts e.g. (32):' The intramolecular version of this process is also successful; heating (33) with aqueous MeNH,.HCl gives (34).4d Ally1 cations can be regarded as double bonds made strongly dienophilic by attachment to a carbonium ion centre. In agreement with this view the allylalcohol (35) and CF3S03H at -23°C give (36) (77'/0).~~Allenes appear to be reactive dienophiles in intramolecular addition^.^^ A particularly pleasing example4g involves reaction of the mixture of allylic bromides (37) with (38) to give (39) en route to sativen.H' (35) (36) (37) D. W Jones Although the intramolecular Diels- Alder reaction commands extremely wide use in synthesis' there are few systematic studies which reveal useful general information about the effect of changes in the 'handle' between diene and dienophile upon the ease and stereoselectivity of the process. The influence of the length of the carbon chain connecting diene and dienophile has been explored for the intramolecular additions depicted in (40) for values of n from 5-11.6" When n = 6 z.e.the new left-hand ring was 6-membered addition occurred at 20 "C but when n = 10 or 11 the thermal reaction failed and catalysis by Me,AlCl was required. For n = 5 and 7 heating at >140 "Cwas needed. The failure of (40; n = 5) to undergo catalysed addition is attributed to the preference of the aluminium complex for an s-trans conformation unsuitable for the addition. Only the addition of (40; n = 5 or 6) showed high stereoselectivity (for a cis ring-junction) and here the stereoselectivity was greater than for the intermolecular reaction. 0 The now well recognized beneficial effect of running some Diels-Alder reactions in water is not accounted for by well established solvent parameters; the accelerating effect of water is too great. However a new solvophobicity parameter set Sp based on the energy changes of noble gases alkanes etc.for transfer from gas to a given solvent successfully correlates the rate of addition of dimethyl fumarate with cyclo- pentadiene in a range of solvents including water.6b The same authors note that whereas P-cyclodextrin inclusion strongly promotes the addition of diethyl fumarate to cyclopentadiene the addition of ethyl acrylate to the same diene is actually retarded by P-cyclodextrin; the result may be due to preferred binding of two molecules of either the diene or the dienophile. Pools of water in clays accelerate additions to furans,6c and the addition of butyl acrylate and acrylonitrile to cyclopen- tadiene is speeded in micelles with accompanying increased endo-selectivity.6d Aqueous Diels- Alder reaction in the presence of P-cyclodextrin provided a vital rate enhancement in the intramolecular addition (41;arrows) allowing preparation of the kinetic product (42) in 96% yield.6' The hetero-Diels-Alder reaction in natural product synthesis has been reviewed.6f Two conditions might be expected to give rise to two-step 1,3-dipolar cycloaddi- tion.When both HO-LU interaction energies are similar the addition is slowest and e.g. P. A. Brown and P. R. Jenkins J. Chem. Soc. Perkin Trans. 1 1986 1303; H. Dyke R. Sauter P. Steel and E. J. Thomas J. Chem. Soc. Chem. Cornmun. 1986 1447; H. J. Reich E. K. Eisenhart R. E. Olson and M. J. Kelly J. Am. Chem. Soc. 1986 108 7791; M. Ladlow P. M. Cairns and P. Magnus J. Chem.Soc, Chem. Cornmun.,1986 1756; S. Handa K. Jones and C. G. Newton ibid. 1986 1797; D. L. Boger and R. S. Coleman J. Org. Chem. 1986 51 3250; K. Shishido K. Hiroya Y. Ueno K. Fukumoto T. Kametani and T. Honda J. Chem. Soc. Perkin Trans. 1 1986 829; K. Fischer and S. Hunig Chem. Ber. 1986 119 2590 3344; K. J. Shea and J. J. Svoboda Tetrahedron Lett. 1986,27 4837. (a) D. A. Smith K. Sakan and K. N. Houk Tetrahedron Lett. 1986,27,4877; H.-J. Schneider and N. K. Sangwan J Chem. Soc. Cbem. Cornmun. 1986 1787; (c) P. Laszlo Acc. Chem. Res. 1986,19,121; (d) R. Brown F. Schuster and J. Sauer Tetrahedron Lett. 1986 27 1285; (e) W. M. Grootaert and P. J. DeClerq Tetrahedron Lett. 1986 27 1731; (f)R. R. Schmidt Acc. Chem. Rex 1986 19 250. Reaction Mechanisms -Pert (i) Pericyclic Reactions a biradical path is expected in the presence of stabilizing substituents.Alternatively if the HO (1,3-dipole)-LU (dipolarophile) interaction is very dominant the other FMO interaction will be very weak and in the extreme it should be overcome by the more favourable entropy of a two-step process. The 1,3-dipole (43) has a high energy HO due to the absence of electronegative atoms and steric effects favour two-step addition. Addition of (43) to the very electron-deficient dipolarophile (44) (low energy LUMO) shows marked non-stereospecificity which increases with sol- vent polarity. The zwitterion (45) is suggested as intermediate and the related zwitterion from (43) and tetracyanoethylene can be trapped with methan01.~" H 'OH (411 (42) (431 Me02C ,CN NC Ji C02Me COzMe (44) (45) Reaction between CD2N and CH20 has been carried out both thermally and phot~chemically.~~ Both reactions give CD20 which is believed to arise via the 1,3-dipole (46).The related dipoles (47) are generated by heating arylchlorodiazirines in acetone and are trapped in the presence of acetylenic ester^.'^ Although secondary interaction would be expected to favour endo-addition of dipolarophiles to nitrones only maleates behave in this way. The exo-adducts are the main products of the kinetically controlled addition of cyclic nitrone (48) to mono-substituted dip~larophiles.~~ Related additions provide useful routes to simple alkaloids7' '(a)R. Huisgen G. Mloston and E. Langhals J. Am.Chem. SOC.,1986,108,6401; R. Huisgen E. Langhals and H. Noth Tetrahedron Lett. 1986 27 5475; (b) G. K. S. Prakash R. W. Ellis J. D. Felberg and G. A. Olah J. Am. Chem. SOC.,1986 108 1341; (c) T. Ibata M. T. H. Liu and J. Toyada Tetrahedron Lett. 1986 27 4383; (d)J. J. Tufariello and J. M. Puglis ibid. 1986 27 1265; (e)J. J. Tufariello and K. Winzenberg ibid. 1986 27 1645; J. J. Tufariello H. Meckler and K. Winzenberg J. Org. Chem. 1986 51 3556; (f)D. L. Boger and C. E. Brotherton J. Am. Chem. SOC.,1986 108 6695; 1986 108 6713; Tetrahedron 1986,42 2777; (g) E. Vedejs and J. W. Grisson J. Am. Chem. SOC.,1986 108 6433; (h) A. Padwa and J. R. Gasdanska ibid. 1986 108 1104; (i) A. Padwa J. R. Gasdanska M. Tomas N. J. Turro Y. Cha and I. R. Could ibid.1986 108 6739. D. W. Jones The fascinating species formulated as (49) arises upon heating the cyclopropenone acetal (50) at 75 "C.In the presence of ketones adducts of type (51) are formed and the related adduct (52) is obtained from dimethyl methoxymethylenemalonate. With methyl acrylate on the other hand the product (53) of carbene-type addition is observed. As befits a highly strained olefin (high energy HO and low energy LUMO) (50) adds 1,4 to dienes substituted with either donor or acceptor groups. Steric effects are held responsible for the failure of (50) to add to a-pyrones at sufficiently low temperature to avoid addition of the ring-opened form (49) which leads to adducts of the type (54) from the Eschenmoser intermediate (55) in the synthesis of colchicine.High-pressure stimulated addition of (50) to a-pyrones proceeds without the intervention of (49).7f A The dihydrooxazolines (56; R" = H) open spontaneously to the azomethine ylides (57). In contrast if R = alkyl aryl etc. eclipsing effects in the planar dipole inhibit ring-opening; the heating of aziridines (58) then gives (56) as stable products.7g With silver fluoride the indoles (59) are believed to give the 1,3-dipoles (60) which can be trapped e.g. with acrylonitrile to give the adducts (61) which then lose Ago and a proton (61; In related work" the nitrile ylide (62) has been generated by AgF-induced elimination of PhSSiMe from the silylthioimidate (63). R RwAkR' 0 R"' (58) (57) R I CH2SiMe CHY Reaction Mechanisms -Part (i) Pericyclic Reactions Pha Me CH,-CAI-CH The bromonitrile oxide (64) can be slowly generated from (65) using solid sodium hydrogen carbonate in ethyl acetate.Trapping is consequently efficient e.g. (66) and its regio-isomer are formed in a CQ. 4 :1 ratio in 86%yield. Even trisubstituted olefins react well8" The method has been used to make epipodophyllotoxin.8b 0-h X-Ray structure determination shows that protonated Ruhemann's purple is the stable N-protonated 1,3-dipole (67) which reacted with several dipolarophiles to give the expected adducts in high yield.8' Reaction of ninhydrin with a-amino-acids in the presence of N-phenylmaleimide gives the adduct type (68) of the N-protonated 1,3-dipole (69) providing evidence for such 1,3-dipoles in the ninhydrin reaction.Sulphinylaminomethanide anions (70) rather than protonated species like (69) are believed to be intermediates in the reaction of thionylaniline with a-amino-acids.8d Ph *(a)P. Caldirola M. Ciancaglione M. DeAmici and C. DeMichaeli Tetrahedron Lett. 1986 27 4647; (b) D. M. Vyas P. M. Skonezny T. A. Jenks and T. W. Doyle ibid. 1986 27 3099; (c) R. Grigg J. F. Malone T. Mongkolaussavaratana and S. Thianpatanagul J. Chem. SOC.,Chem. Commun. 1986 421; (d) R. Grigg M. Dowling and V. Sridharan ibid. 1986 1777; (e) E. Vedejs and C. K. McClure J. Am. Chem. SOC.,1986,108,1094; (f)K. N. Houk,H.-Y. Duh Y.-D. Wu and S. R. Moses ibid. 1986,108,2754. D. W Jones Hyperconjugative effects of allylic substituents were found to be unimportant in determining facial selectivity in the osmylation of allylic silanes sulphones sul- phides silyl ethers and acetates.8e Osmium ligand effects are suggested as being important and for 2-double bonds an alkoxy-anti alkyl-outside conformation is preferred.These results conflict with earlier suggestions made by Houk about the preference of an alkoxy-group for the inside position in addition TS's. The latter group have now studied the addition of nitrile oxides to the olefins (71) where R' is larger than R2;the adduct (72) was more important than (73). If (71) reacted in its ground-state conformation (shown) this would require preferred approach to the more hindered face and increasing selectivity for this face as the size of R' increased.The major product is therefore believed to arise via the staggered TS (74) with the largest group (L) anti and the medium-sized.group in the inside position. The minor product arises via TS (75). For allylic ethers the alkoxy-group takes the place of M in (74) although this probably occurs to minimize electron repulsion between the allylic oxygen and the nitrile oxide oxygen rather than to reduce electron withdrawal from the double bond as postulated earlier.*J y-/H R' H-C R2 The formal (4 + 4)-dimerization of (76; R = R' = H) to (77) is probably a two-step process with a biradical (78) as intermediate; (76; R = D R' = H) dimer- izes ca. six times more slowly than (76; R = H R' = D).9a A similar biradical intermediate is proposed for formation of both the formal (4 + 2)-and (4 + 4)-dimers of 0-q~inodimethane.~' Intramolecular (6 + 4)-addition to the tropone nucleus has been studied with a view to the synthesis of Ingenane diterpenes.Like the intermolecular reaction the intramolecular one is exo-selective (79) giving (SO)." Both intramolecular (6 + 4)-9d and (8 + 6)-addition9" can be observed with fulvenes as 67r components. Vinylogous urethanes like (81) lose ethanol upon FVP at ca. (a)C. H. Chou and W. S. Trahanovsky J. Am. Chem. SOC., 1986 108,4138; (b)W. S. Trahanovsky and J. R. Macias ibid. 1986 108 6820; (c) R. L. Funk and G. L. Bolton ibid. 1986 108 4655; J. H. Rigby T. L. Moore and S. Rege J. Org. Chem. 1986 51 2398; (d) Y. N. Gupta R. T. Patterson A. Z. Bimanand and K.N. Houk Tetrahedron Lett. 1986 27 295; (e) C.-Y. Liu D. A. Smith and K. N. Houk ibid. 1986 27 4881; (f)F. Arya J. Bouquant and J. Chuche ibid. 1986,27 1913; (g) J. Mann Tetrahedron 1986 42 4611; (h) H. R. Seikaly and T. T. Tidwell ibid. 1986 42 2587; (i) H. D. Roth Editor ibid. 1986 42. Reaction Mechanisms -Part (i) Pericyclic Reactions R 400 "C to give vinylketenes which undergo intramolecular (2 + 2)-addition (82; arrows).9f The synthetic utility of oxyallyl cationsgg and the addition reactions of ketenesgh have been reviewed and the structure and reactivity of organic radical cations has been the subject of a Symposium in Print.g' 3 Sigmatropic Reactions A non-randomized biradical intermediate (83) in the thermolysis of deuterium labelled ( -)-(S)-a-pinene (84) will explain the D-distribution in the products [( f )-limonene alloocimene and a little (R)-a-pinene] as well as the effect of the label in reducing the quantity of ( * )-limonene formed whilst not slowing the disappearance of (84).''' Biradical intermediates have also been suggested for D3cr D3C CH3 0 several other apparent 1,3-shifts.lob Although walk rearrangement in the bicyclo[2.1 .O]pentane system proceeding with inversion at C-5 could involve a biradical intermediate (85) this would have to be different from the biradicals generated by photolysis of pyrazolines like (86); the biradical (87) formed from the latter undergoes bonding between C-5 and both C-1 and C-3 and in both cases the side of C-5 originally bonded to nitrogen is (a) J.J. Gajewski and C. M. Hawkins J. Am. Chem. SOC., 1986 108 838; (b) J. W. Barton and M. K. Shepherd J. Chem. SOC.,Perkin Trans. 1 1986 961; X. Creary and M. E. Mehrsheikh-Mohammadi J. Org. Chem 1986,51 1110; B. Miller and J. Bagdadchi J. Chem. SOC.,Chem Commun. 1986 1257; M. Christl C. Herzog and P. Kemmer Chem. Ber. 1986 119 3045; (c) F.-G. Klarner V. Glock and H. Frigge ibid. 1986 119 794; (d) R. M. Jarret M. Saunders S. Pikulin and J. A. Berson J. Am. Chem. SOC.,1986 108 2768; (e) P. de Mayo and G. Wenska J. Chem. SOC.,Chem. Commun. 1986 1626. D. W. Jones MeOCH2 D The cation (88) undergoes walk rearrangement (1,4-sigmatropy) much more rapidly than (89). This may be associated with a dicyclopropylcarbinyl cation (90) as intermediate or TS; the failure of (88) to give the benzyl cation is presumably due to the requirement of a conrotatory electrocyclic ring-opening.lod Irradiation (A > 420nm) of (91) and suspended CdS induces a 1'3-hydrogen shift to (92).loe This presumably involves the radical-cation of (91 ) produced by electron-transfer to a 'hole' photogenerated in the semi-conductor.dH2 Arrhenius parameters and a primary kinetic isotope effect (kH/kD = 6.3-7.6) for the fast 1'5-hydrogen shift to the central carbon of an allene (93; arrows) points the similarity of this process to simple 1,Shydrogen shifts."" The sulphone (93; R' = SO,Ph R = H) and the sulphoxide (93; R' = SOPh R = H) rearrange ca. 700 and ca. 100 times more rapidly than (93; R' = R = H).Moreover a But group and a sulphoxide favour migration of hydrogen to different faces of the allene double bond; the But group favours migration to the lower face [Hb migration in (93)] to give (94) whilst the SOPh group favours migration to the upper face (Ha migration) to give (95),llb Although generated at 0 "C (96) is not detectable. Instead (97) the product of an extremely easy 1,Sbenzyl shift is obtained.'lc The order of migratory aptitude RSO > RS -H > RS02 > RCO > C0,Et has been deter- mined for the 1,5-shift in e.g. the transient species (98).'ld In related carbocyclic systems formyl and acetyl groups migrate faster than hydrogen and direct conversion '' (a) S. A. Barrack and W. H. Okamura J. Org. Chem. 1986 51 3201; (6) W.H. Okamura G.-Y. Shen and R. Tapia J. Am. Chem. SOC.,1986 108 5018; (c) B. Miller and J. Baghdadchi J. Chem. Soc. Chem. Commun. 1986 511; (d) R. S. Gairns C. J. Moody and C. W. Rees J. Chem. SOC.,Perkin Trans. 1 1986 501; (e) M. J. Collett D. W. Jones and S. J. Renyard ibid. 1986 1471; P. J. Battye and D. W. Jones ibid. 1986 1479; (f)J. J. Gajewski A. M. Gortfa and W. T. Borden J. Am. Chem. SOC.,1986 108 1083. Reaction Mechanisms -Purr (i) 'Pericyclic Reactions of (98; Y = H) into product (99) by prototropy rather than via 1,5-sigmatropy is a possible explanation. Full papers have appeared dealing with the very different relative migratory aptitudes of doubly and triply bonded groups about cyclopen- tadiene and cycloheptatriene systems.'le.Thermolysis of (100) gives first the products of formal 1,5-shift (101) and its C-7 epimer in a ratio of 3 1; (101) involving forbidden inversion of the migrating carbon is dominant. Accordingly it is proposed that rearrangement involves a biradical intermediate.' Substitution of deuteriums at the terminal methylene carbons of (102) allowed measurement of a bond-making KIE in the boat-like Cope process (102; arrows). This indicated 25% bond-making at the TS. This value compares with one of cu. 67% in chair-like acyclic rearrangement and rules out significant intervention of the biradical (103) as intermediate or TS.'*" Attempts to prepare sulphoxides of type (104) by oxidation of the related sulphides gave instead the sulphines (105) derived Me$T"2-j .-&/ & Me' f.-CH2 Me b (102) (103) (104 (105) (a) J.J. Gajewski and J. L. Jimenez J. Am. Chem. Soc. 1986 108 468; (b) E. Block S. Ahmad J. L. Catalfamo M. K. Jain and R. Apitz-Castro ibid. 1986 108 7045; J. R. Hwll and D. J. Anderson Tetrahedron Lett. 1986 4965; (c) K. J. Shea S. C. Greerley S. Nguyen P. D. Beauchamp D. H. Aue and J. S. Witzeman J. Am. Chem. Soc. 1986 108 5901; (d) N. Eisen and F. Vogtle Angew. Chem. Int. Ed. Engl. 1986 25 1026. D. W. Jones by rearrangement (104; arrows). Although (104) could use the accelerating effect of both the sulphonium salt and anionic oxy-Cope rearrangements it rearranges only 45 times faster than the sulphide in the absence of acid.'2b Cope rearrangement of systems of the type (106) where m is 1 or 2 and n is 3 or 4 provides a route to several meso-bridged dienes (107).The rearrangement rates do not correlate with relief of strain. More likely the high HOMO energy of the bridgehead bond when rn = 1 or 2 is an important factor.12' On the other hand ring-strain is believed to induce the Cope-rearrangement (108; arrows) converting an 11-membered into a 15-membered ring.'2d The stereochemistry of Claisen and related processes has been explored'3a and contrary to the general view some tertiary allylic alcohols participate in such rearrangements with good stereochemical contr01.'~ The Ireland-Claisen rearrange- ment (109; arrows) is a key step in a synthesis of q~adrone'~' and the use of large-ring lactones in these reactions has been explored'3d en route to dicotyl diterpenes.Amusingly the planned conversion of (1 10) into (1 11) via Claisen rearrangement failed. Instead (1 10) underwent reverse (4 + 2)-addition to (1 12) which then gave (1 11) by intramolecular (4 + 2) additi~n!.'~' RO,C 02 Ro2ca R3si0& IH'Et \ /i 'Et Et Whilst the lithium enolate (1 13; M = Li) undergoes 2,3-sigmatropic shift to (114) the silylketene acetals (1 13; M = SiMe,Bu') undergo 3,3-shift (1 13; The l3 (a) G. W. Daub and D. A. Griffith Tetrahedron Lett. 1986 27 6311; G. W. Daub P. L. Shanklin and C. Tata J. Org. Chem. 1986 51 3402; C. S. Wilcox and R. E. Babston J. Am. Chem. SOC.,1986 108 6636; (6) A. H. Davidson and I. H. Wallace J. Chem. SOC.,Chem. Commun. 1986 1759; (c) R. L. Funk and M.M. Abelman J. Org. Chem. 1986,51,3247; (d) N. J. Begley A. G. Cameron and D. W. Knight J. Chem. SOC.,Perkin Trans. 1 1986 1933; A. G. Cameron and D. W. Knight ibid. 1986 161; (e)S. D. Burke D. A. Armistead and K. Shankaran Tetrahedron Lett. 1986 27 6295. (a) S. Raucher and L. M. Gustavson Tetrahedron Lett. 1986 27 1557; (6) M. C. Pirrung and J. A. Werner J. Am. Chem Soc. 1986 108 6060; E. J. Roskamp and C. R. Johnson ibid. 1986 108 6062; (c) K. Mikami 0.Takahashi T. Tabei and T. Nakai Tetrahedron Lett. 1986,27,4511; (d)T. Takahashi H. Nemoto Y. Kanda and T. Tsuji J. Org. Chem. 1986 51 4315; J. A. Marshall T. M. Jenson and B. S. DeHoff ibid. 1986 51 4316; (e) M. Uchikawa T. Hanamoto T. Katsuki and M. Yamaguchi Tetrahedron Lett. 1986 27 4577 Reaction Mechanisms -Part (i) Pericyclic Reactions 0 oxygen ylides (1 15) generated by Rh" catalysed decomposition of the diazoketones (116) undergo 2,3-shift (115; arrows) to 5- 6- and 8-membered oxygen heterocycle^.'^^ Similar oxygen ylides may be intermediates in the reaction of the ally1 ethers (117) with trimethylsilyl triflate-Et,N which gives the Wittig rearrange- ment products (1 18).14' A 2,3-Wittig ring-contraction (1 19; arrows) has been explored in routes to cembranoids and cost~nolide.'~~ Asymmetric 2,3-rearrange- ments of the related amides (120) proceed with high syn-diastereo and diastereo-face ~e1ection.l~~ 0.!OMOM 4 Electrocyclic Reactions The preference of a wdonor substituent for outward rotation in cyclobutene ring- opening has been examined for (121).The conrotatory mode-1 [see arrows in (121)] involves inward rotation of only one fluorine atom whilst mode-2 involves inward rotation of two fluorine atoms. The first mode is favoured over the second by ca. 13 kcal mol-' in good agreement with a predicted value of 13 kcal mol-' for the activation energy difference for outward and inward rotation of a single fluorine High temperature equilibrium constants for the valence tautomerism of l5 (a) W. R. Dolbier H. Koroniak D. J. Burton and P. Heinze Tetrahedron Lett. 1986 27 4387; (b) M. E. Squillacote and A. Bergman J. Org. Chem. 1986 51 3910; (c) K. Schishido K. Hiroya K. Fukumoto and T. Kametani Tetrahedron Lett. 1986,27,971; (d) K. Schishido K. Hiroya H.Komatsu K. Fukumato and T. Kametani J. Chem. SOC.,Chem. Commun. 1986,904; (e)A. Hassner and S. Naidorf Tetrahedron Lett. 1986 27 6389; (f)L. S. Leibskind S. Iyer and C. F. Jewell J. Org. Chem. 1986 51 3065; S. T. Perri L. D. Foland 0. H. W. Decker and H. W. Moore J. Org. Chem. 1986 51 3067; (g) R. L. Danheiser S. K. Gee and J. J. Perez J. Am. Chem. Soc. 1986 108 806. D. W. Jones cyclo-octatetraene and bicycle[ 4.2.0loctatriene have been determined by rapid cool- ing of high temperature mixtures. Extrapolation of the results to 100 "Cgives a AGO value of 7.1 kcal mol-' in good agreement with an earlier indirect estimate (AGO 6.8 kcal m~l-').'~~ Heating (122) at 180 "C results in a fascinating sequence of electrocyclic ring-opening to (123) ring-closure to ( 124) and Claisen rearrangement to (125).lSc The general scheme has been used in alkaloid ~ynthesis.'~~ \ Me The thermal ring-opening of cyclobutenones to vinylketenes is well established.The corresponding photo-reaction has now been shown to have advantage^.'^^ Irradiation of (126) (A = 300 nm) gives the vinylketene (127) which is long-lived and may be efficiently trapped several minutes after irradiation has ceased. Trapping with isopropene is now successful whereas in the thermal process polymerization intervened. Adduction is regiospecific but mixtures of stereoisomers are formed. Whereas .rrf + 7:approach of ketene and olefin should give mostly cis-product e.g. (1 28) from cyclohexa- 1,3-diene the thermal reactions give mostly trans-products.The photogenerated ketene gave mostly (128) which was shown to be converted in c1 c1 C15 \ Ph Phb c15ph 0 o+C Reaction Mechanisms -Part (i) Pericyclic Reactions part into its 2,3-trans isomer on heating. Cyclobutenone ring-opening provides a useful route to q~inones.'~~ Thus the derivatives (129) ring-open with well preceden- ted outward rotation of the donor group (OH) to give the vinylketenes (130) which ring-close to (131); tautomerism and oxidation then gives naphthoquinones. The Ar group in (129) may be replaced by a vinyl group or a heterocyclic substituent. Pride of place for ingenuity in the use of vinylketenes must go to Danheiser and his collaborator^.'^^ The vinylketene (1 32) generated from the related cyclobutenone at 120 "C adds to the electron-rich acetylene (133) to give cyclobutenone (134) which ring-opens to (135).Electrocyclic ring-closure (135; arrows) and prototropy then gives (136) which can be readily converted into mycophenolic acid in 17-19'/0 overall yield. R 0 ,I,f II Me0I CH20CH20Me L+ CH,OCH,OMe (133) (132) (134) Me (135) (136) R = E-CH,CH=C(Me)(CH,),OSiMezBu'