4 Reaction Mechanisms Part (i) Pericyclic Reactions By R. S. ATKINSON Department of Chemistry University of Leicester Leicester LEI 7RH 1 Electrocyclic Reactions A helical transition state (I) is suggested for the 877 -+ 677 conversion of diazo- alkadiene (2) into the diazepine (3).' This geometry (reminiscent of the [1,7]sig-matropic rearrangement of hydrogen) it is claimed requires less distortion of the diazoalkane and accounts for the alternative pathway followed (67r -B 47r cycliza-tion) when R2 = Me. (65-9 3 % ) More compelling evidence for helicity involvement in an electrocyclic reaction comes from thermolysis of (E)-and (2)-2-butenedioates (4)and (5) respectively.* In each case two substituted pyrrolizine stereoisomers are formed by [1,6] sigmatropic rearrangement of deuterium followed by 677 -B 477 ring-closure of the 1,5-dipole.There is stereospecificity in the formation of (6)-(9) which is revealed by the different chemical shifts of the CHDC02Me protons as indicated and the logical conclusion is that there is no equilibration of the clockwise and anti-clockwise helices from which the [1,6] sigmatropic rearrangement has taken place. The authors assume that electrocyclic ring-closure from these helices is invariably disrotatory and to account for the formation of (6) and (8) postulate that stereomutation within the 1,5-dipole [ fi in (lo)] takes place without interconversion of the helices. This seems remarkable and these results could perhaps be better accommodated by assuming competitive disrotatory ring-closure and direct carbanion-iminium cation combination within the I $dipole (but still without interconversion of the two helices involved).' I. R. Robertson and J. T. Sharp J. Chem. SOC.,Chem. Commun. 1983 1003. ' D. N. Reinhoudt G. W. Visser W. Verboom P. H. Benders and M. L. M. Pennings J. Am. Chem. Soc. 1983. 105. 4775. 47 R. S. Atkinson E D D (4) (5) E = C0,Me 1) b 6 CHDE (4) R'= E R2 = H + (6) 6 2.77 + (7) 6 3.12 (5) R'= H R2= E (8) 6 3.99 + (9) 6 2.97 Comparison of electrocyclization rates for the donor-acceptor substituted trienes (1 1) with that of 1,2-divinylcyclohexene shows that the donor-acceptor properties of the substituents have very little influence on the rate of cyclization.' R COzEt (1 1 ) R = H Ph or p-MeOC,H4 2 Cycloaddition Reactions Without doubt this is the age of the intramolecular cycloaddition and the intramolecular [47r + 27~1 in particular.Ingenious and delightful syntheses of com- plex natural products or models for natural product synthesis using intramolecular Diels-Alder and intramolecular 1,3-dipolar cycloaddition reactions continue to appear in profusion. There has been little evidence of a sktckening of interest in the inter-molecular Diels-Alder reaction in the past year either. The ideal diene (or set of dienes) for the Diels-Alder should of course possess the following attributes (a) be regio- specific (in either sense as required) (b)be endo (or exo?) stereospecific (c) be perispecifically reactive as the 47r component under the mildest stimulation with least reactive dienophiles (d)offer versatility for functional group interconversion in the cycloadduct (e)yield only one diastereoisomer when reacted (in chiral form) with a prochiral dienophile.The ideal matching set of dienophiles would have E. N. Marvell C. Hilton and M. Cleary J. Org. Chem. 1983 48 4272. Reaction Mechanisms -Part (i) Pericyclic Reactions identical attributes mutatis mutandis. A set of dienes/dienophiles is required not least to satisfy the inherently different requirements of the normal and inverse Diels-Alder reactions. Much of present work in this area is in practice an examination of regioselectivity effects [(a) above] resulting from changes in diene/dienophile catalysis or reaction conditions.Although prediction of regioselectivity has been available for some years using frontier molecular orbital (FMO) theory it has also been recognized that neglect of secondary orbital interactions could lead to erroneous conclusions. For certain Diels-Alder reactions notably (12) with methyl vinyl ketone it has been shown that regioselectivity is dominated by secondary orbital interaction^.^ The corollary which follows from the above that there should be a direct link between regioselectivity and endo-stereoselectivity [(a)and (b)above] has also been recognized for some time but not explored. Dienes (13) are ambident reacting both Me0 8-20 kbar PhSfi CO,R1 - OR2 rl-" '"* with dienophiles substituted with electron-accepting (A) and electron-withdrawing (D) groups.It has been found that application of high pressure brings about reaction at room temperature and that the (thermally unstable) adducts are formed with high regioselectivity and endo-~electivity.~ NHC0,R (14) X = SPh (15) X = SOPh (16) X = S0,Ph x The acylamino group in the new (stable and crystalline) dienes (14)-( 16) has been found to exercise powerful regio-control in reactions with a#-unsaturated carbonyl compounds dominating the effects of a sulphur substituent at position 4 whether this be sulphenyl sulphinyl or sulphonyl endo-stereospecificity is also high.6 It is claimed that this dominance by the acylamino group is not rationalized by conven- tional FMO considerations.The cycloadducts from (14)-( 16) and e.g. acrolein score well on (d) above -versatility in functional-group interconversion in the cyclohexene adduct. P. V. Alston M. D. Gordon R. M. Ottenbrite and T. Cohen J. Org. Chem. 1983 48 5051. G. Revial M. Blanchard and J. d'Angelo Tetrahedron Lett. 1983 24 899. ' L. E. Overman C. B. Petty. T. Ban. and G. T. Huang J. Am. Chem. Soc. 1983. 105. 6335 R. S. Atkinson In contrast the regioselectivity of addition of (17) to glyoxylate esters can be reversed by the apparently slight modification as in (1 8). This reversal of regioselec-tivity has been exploited in a synthesis of uranicine (19).7 o-Quinodimethanes will always be popular because of their reactivity [(c) above] and the route for their generation as in (20) has been extended to obtain (21)8 and (22).' F -3 SiMe R' I SiMe CsF -SiMe Additional dienes which have been prepared with a view to their use in Diels-Alder reactions include (23)-(26).10-13 (PhSe) (23) Hal = C1 or Br R = H or C1 ' R.R. Schmidt and A. Wagner Tetrahedron Lett. 1983 24 4661. ' Y. Ito Y. Amino M. Nakatsuka and T. Saegusa J. Am. Chem. Soc. 1983 105 1586. ' Y. Ito E. Nakajo M. Nakatsuka and T. Saegusa Tetrahedron Left. 1983 24 2881. lo A. J. Bridges and J. W. Fischer Tetrahedron Lett. 1983 24 445. " T. Minani H. Sako T. Ikehira T. Hanamoto and I. Hirao J. Org. Chem. 1983 48 2569. '' A. V. Rama Rao G. Venkatswamy S. M. Javeed V. H. Deshpande and B. Ramamohan Rao J. Org. Chem. 1983 48 1552.E. Negishi and F.-T. Luo J. Org. Chem.. 1983 48 1560. Reaction Mechanisms -Part ( i) Pericyclic Reactions R' Z ,c=c, \/ + C5H11y Pd(PPh,) H M X Z Z = OEt SEt or SiMe R' M = ZnC1 AIR, or BR,Li (26) X = Br or I Regiospecific preparation of 3-or 4-substituted 2,6-dimethylbenzoates is accom- plished by reaction of the pyrone (27) with morpholinoenamines. By using the appropriate enamine either of the isomeric benzoates may be obtained as a single pr~duct.'~ 0 CO,R (27) (50%) "'0"' Ph One of the sternest challenges in (C=C) dienophile design is to find surrogates for alkyl-substituted alkenes (which are notoriously unreactive in the intermolecular Diels-Alder). Synthons for ethylene or 1-alkenes and acetylene or monosubstituted alkynes are (28) and (29) respecti~ely.'~ Phenyl vinyl sulphone is a moderately reactive dienophile is particularly effective in regio-control and after [4~ + 2~1 cycloaddition is easily reductively removed (29) is an alkyne synthon since treatment of its adducts with 4~ systems with fluoride ion restores a double bond with elimination of trimethylsilicon and sulphonyl groups.Me,Si -SO,Ph -SO,Ph (28) (29) Introduction of the sulphonyl group likewise increases the dienophilicity of other alkenes and this is accomplished using phenylseknenyl benzene sulphonate (Scheme l)." MeoJ+ SO,R Reagents i PhSeSO,Ph hv; ii H,OI; iii OSiMe iv H,Of; v Zn-HOAc Scheme 1 j4 H. L. Gingrich D. M. Roush and W. A. Van Saun J. Org.Chem. 1983 48 4869. l5 R. V. C. Cam R. V. Williams and L. A. Paquette J. Org. Chem. 1983 48 4976. '' W. A. Kinney G. D. Crouse and L. A. Paquette J. Org. Chem. 1983 48 4986. R. S. Atkinson The compound trans-1,2-disulphonyletheneis also reactive in normal Diels-Alder reactions and an ethylene synthon." Surprisingly high dienophile reactivity is exhibited by Fischer carbene complexes (30) which react at rates 104-timesgreater than methyl acrylate. The potential of the metal complex residue iii the cycloadducts for conversion into other functional groups is considerable.'8 (70%) A number of new chiral dienophiles (31)-(33) have been introduced which with cyclopentadiene yield adducts with high enantiospecificity [(e)ab~ve].'~-~' 0-\ Bu' \ Ro (31) (32) K XJ,IY rrz or S0,Ph R = SO,NPr;orSO,Ph (33) Recent recognition of the carbonyl group as a useful dienophile under the influence of catalysis by Lewis acids has been exploited to good effect as the first step in a synthesis of amino-octose derivatives (iincosamine) (Scheme 2).23 I OMe Scheme 2 A remarkable observation in this heter~-Diels-Alder*~ reaction is that the role of the Lewis acid catalyst can be assumed by 'oxaphilic' shift reagents e.g.Eu(fod), " 0. De Lucci and G. Modena Tetrahedron Lett. 1983 24 1653. l8 W. D. Wulff and D. C. Yang J. Am. Chem. SOC.,1983 105 6726. l9 W. Oppolzer and C. Chapuis Tetrahedron Lett. 1983 24 4665. 20 W. Choy L. A. Reed and S. Masamune J. Org. Chem. 1983 48 1137; S.Masamune L. A. Reed J. T. Davis and W. Choy ibid. 1983 48 4441. 'I W. Oppolzer C. Chapuis and M. J. Kelly Helv. Chim. Acta 1983 66,2358. 22 See also D. Horton T. Machinami Y. Takagi C. W. Bergmann and G. C. Cristoph J. Chem. SOC. Chem. Commun. 1983 1164; P. A. T. W. Porskamp R. C. Haltiwanger and B. Zwanenburg Tetrahedron Lett. 1983 24 2035. 23 E. R. Larson and S. Danishefsky J. Am. Chem. SOC. 1983 105 6715. 24 For a review of the synthetic aspects of Diels-Alder additions with heterodienophiles see S. Weinreb and R. R. Staib. Tetrahedron. 1982 38 3087. Reaction Mechanisms -Part (i) Pericyclic Reactions 53 and asymmetric induction in the product is brought about when the ligands on the shift reagent are chiral e.g. E~(hfc)~.~~ Thioaldehydes are unstable species which are nevertheless well-behaved dienophiles in normal Diels-Alder reactions.Their regioselectivity of reaction with electron-rich dienes for Z = alkyl (Scheme 3 path a) is reversed with Z = acyl or cyano (path b).26 R= SiMe,Bu' Ib Z Scheme 3 A number of new routes to ethoxycarbonyl-substituted thioaldehydes (thio-oxa- acetates) have been devised.27 The importance of pressure effects on the Diels-Alder reaction is increasingly receiving recognition. Furan and benzoquinone react to give endo-and em-products under high pressure,28 but both of the latter are unstable at room temperature and pressure which explains why these adducts have not previously been obtained (Scheme 4). Increased pressure affects not only rates of reaction but also endo exo ratios in addition of benzoquinones to f~rans.~~ ST,12h.I bar + -8 "C I bar ov Scheme 4 25 M. Bednarski and S. Danishefsky J. Am. Chem. SOC.,1983 105,6968; M. Bednarski and S. Danishefsky ibid. 1983 105 3716; M. Bednarski C. Maring and S. Danishefsky Tetrahedron Lett. 1983 24 3451. 26 E. Vedejs D. A. Perry K. N. Houk and N. G. Rondan J. Am. Chem. SOC.,1983 105 6999. 27 G. M. Bladon I. E. G. Ferguson G. W. Kirby A. W. Lochead and D. C. McDougall J. Chem. Soc. Chem. Commun. 1983 423; G. W. Kirby and A. W. Lochead ibid. 1983 1325. 28 J. Jurczak T. Kozluk S. Filipek and C. H. Eugster Helv. Chim. Acta 1983 66 222. 29 J. Jurczak T. Kozluk M. Tkacz and C. H. Eugster Helu. Chim. Acta 1983 66 218.54 R. S. Atkinson In the Lewis-acid catalysis of the reaction of quinones with alkyl-substituted butadienes TiCI (at -78 "C)brings about the same regioselectivity as in the thermal reaction (at 200 "C) but BF3 catalysis gives the opposite regioselectivity. It is suggested that a different site in the quinone may be complexed in each case.3o Further striking examples of the accelerated rates of some Diels-Alder reactions in water have a~peared.~' Considerable efforts have been made to try to understand facial stereoselectivity of dienes (34)-(37) which are grafted on to a [2.2.1] skeleton. The face which is preferentially attacked by dienophiles is not necessarily that predicted on the basis of steric effects and the selectivity has been ascribed to r-lobe tilting of the sub-HOMOS (subjacent) resulting from u/T coupling.32 Other factors are held to be responsible in the case of (38).33 ,Me pJ (34) (35) (37) A number of cation radicals of some dienes show exceptional reactivity as dienophile components in the Diels-Alder reaction (Scheme 5).Though still in a primitive state of development this concept is intere~ting.~~ OMe A I 71% endo:exo = 2:l OMe Scheme 5 Heating the ring-fused oxazines (39) in xylene generates the corresponding nitroso- olefins whose Diels-Alder diene and/or 1,3-dipolar character has also been 30 J. B. Hendrickson and V. Singh J. Chem. SOC.,Chem. Commun. 1983 837. 3' P. Grieco P. Garner and Z. He Tetrahedron Lett. 1983,24 1897 R. Breslow U. Maitra and D.Rideout ibid. 1983 1901; P. A. Grieco K. Yoshida and P. Garner J. Org. Chem. 1983 48 3137. 32 L. A. Paquette P. Charumilind M. C. Bohm R. Gleiter L. S. Bass and J. Clardy J. Am. Chem. Soc. 1983 105 3136; L. A. Paquette P. C. Hayes P. Charumilind M. C. Bohm R. Gleiter and J. F. Blount ibid. 1983 105,3148; L. A. Paquette A.-G. Shaefer and J. F. Blount ibid. 1983 105,3642; L. A. Paquette T. M. Kravetz M. C. Bohm and R. Gleiter J. Org. Chem. 1983 48 1250. 33 M. Avenati and P. Vogel Helv. Chim. Acta 1983 66 1279. 34 R.A. Pabon D. J. Bellville and N. L. Bauld J. Am. Chem. SOC.,1983 105 5158. 15 D. E. Davis and T. L. Gilchrist J. Chem. SOC. ferkin Trans. I 1983 1479 T. L. Gilchrist and T. G. Roberts ibid. 1983 1283 D. E. Davies T. L. Gilchrist and T.G. Roberts. ihid. 1983 1275. 55 Reaction Mechanisms -Part (i) Pericyclic Reactions (39) R = COMe CO,Et or Ph An elegant synthesis of 3,4,5,6-substituted cyclohexene derivatives (40) used the proximity of the anthracene nucleus to direct stereospecificity/ regiospecificity of attack on the benzoquinone-derived moiety. Accelerated retro-Diels-Alder reaction takes advantage of the 'oxido effect' which results in a sloughing off of the anthracene at room temperat~re.~~ ,? OR ' Turning to 1,3-dipolar cycloadditions ;the use of N-trimethylsilylmethyl iminium salts as precursors for azomethine ylides has been improved by using thiolactams (Scheme 6).37Variations on this original method include those in Schemes 7 and 8.38 S STf C0,Me ___ (66'/o ) Reagents i MeOTf; ii CsF; iii CH,=CHCO,Me Scheme 6 XR p"y i,ii Ph& + phbE Me X = SMe or OEt Me Me (E = C0,Me) Reagents i Me3SiCH20S02CF3;ii CsF ECHLCHE Scheme 7 A non-stabilized azomethine ylide is believed to be intermediate in the formation of pyrrolidine (41) from trimethylamine oxide,39 This reaction has the hallmarks of a concerted reaction and even normally sluggish 1,3-dipolarophiles are reactive.36 S. Knapp R. M. Ornaf and K. E. Rodriques J. Am. Chem. SOC.,1983 105 5494. 37 E. Vedejs and F. G. West J. Org. Chem. 1983 48 4773. 38 A. Padwa and Y. Y. Chen Tetrahedron Lett. 1983 24 3447; A. Padwa G. Haffmanns and A. Tomas; T. Livinghouse and R.Smith J. Chem. SOC. Chem. Commun. 1983 210; R. Smith and T.Livinghouse J. Org. Chem. 1983 48 1554; see also S. Chen J. W. Ullrich and P. S. Manano J. Am. Chem. SOC. 1983 105 6160. 39 R. Beugelrnans G. Negron and G. Roussi J. Chem. Soc. Chem. Commun. 1983 31. R. S. Atkinson Scheme 8 Me\+/ Me + 7 LiNfii, N OR /\ R R = n-C,H, 63% -0 Me N Me (41) cis-Cyanohydroxylation or cis-carboxyalkylation of alkenes is accomplished by cleavage of their isoxazoline-nitrile oxide adducts (42) and (43) re~pectively.~' 0-)+lilN+ -___* NaOH I -R R 5"yo" C I CN CN CN CO H (42)R = Ph 77% dipole dipolarophile 1 :3 0-I 0+ Ill -O~OTHP bHooco2H N+ C I CH20THP (43) Replacement of the sulphonyl group in isoxazolines (44) by organolithiums makes these more versatile 1,3-hydroxycarbonyI ~ynthons.~' 0-R' R' R3 R' (44) R3 = alkyl aryl alkenyl 0-alkyl or CN Nitrilimine (45) is the first monosubstituted member of this class to be intercepted by dipolarophile~.~~ 40 A.P. Kozikowski and M. Adarnnyk J. Org. Chem. 1983 48 366. 41 P. A. Wade H.-K. Yen S. A. Hardinger M. K. Pillay N. V. Amin P. D. Vail and S. D. Morrow J. Org. Chem. 1983 48 1796; see also A. P. Kozikowski B. B. Mugrage B. C. Wang and Z. Xu Tetrahedron Lett. 1983 24 3705; D. P. Curran J. Am. Chem. SOC.,1983 105 5826. 42 R. Huisgen W. Fliege and W. Kolbeck Chem. Ber. 1983 116 3027. Reaction Mechanisms -Part ( i) Pericyclic Reactions 57 H 0,NCH =N-NPh A [HC-A-NPh] / Na' Normal nitrone regioselectivity is believed to be LUMO (nitrone) controlled until the dipolarophile becomes very electron-deficient or the nitrone becomes very electron-rich.Dicyclopropyl- N-methylnitrone (46) has a lower ionization potential (higher HOMO) due to the electron-donating ability of the cyclopropyl rings and reaction with electron deficient dipolarophiles results in inversion of normal regioselectivity since the addition is now HOMO (nitrone) controlled.43 Cycloaddition of the nitrone (47) to ethyl vinyl ether gives the isoxazolidine (48) as a single diastereoisomer which has been converted in one step into the methyl glycoside of daunosamine (49).44 Me HO NH2 MFoH (47) 93% (48) The facile generation of thiobenzophenone S-methylide (50) by extrusion of N2 from the thiadiazoline (51) even at -45 "C has allowed a study of the character of this 1,3-dipole in its reactions with various C=S C=C C=C and N=N bonds.The relative rate constants for cycloaddition (obtained by using competition experi- ments) have been shown to vary over a range of 10' and the high selectivity of this dipole has been rationalized using Sustmann's cla~sification.~~ 43 A. Z. Bimanand and K. N. Houk Tetrahedron Lett. 1983 24 435. 44 P. Deshong and J. M. Leginus J. Am. Chem. Soc. 1983 105 1686. 45 L. Xingya and R. Huisgen Tetrahedron Lett. 1983. 24 4181. 4185. R. s. Atkinson Ph +N, p2 N (51) (50) The hitherto unknown 1,2,3-triazolidine ring-system has been prepared by CYC~O-addition of azimine (52) to enamines. X-Ray data on (53) show that the three nitrogen atoms are Y .\yo P 0 Oy00 0 >-OAN ?'-\ N /=( d e+o y-7-?' (52) 0 (53) The reactivity of tetrafl~oroalkene,~' and ~inylsilanes~~ cy~loalkenynes,~~ towards various I ,3-dipoles has been probed.3 Other Cycloadditions Attempted intramolecular [67~+ 477-1cycloaddition of the dienyl-fulvene (54) at 210 "C for 48 h yielded a gross mixture from competing [47~+ 277-1 and [677 + 4r] cycloadditions. In accordance with theoretical predictions the greater reactivity of the diethylaminodienyl-fulvene(55) resulted in [6~ + 4r]periselectivity (at 40 "C for 12 h) and the overall transformation after dehydrogenation is an azulene fused to a third ring." K -NEt S b __* 40 "(' R (54) R = H (55) R = NEt Intramolecular [8 T + 2 7~1 cycloaddition of the heptafulvene with the 'tetraenophilic' double bond in (56) results in (57)as the major product calculations support (56) as the preferred transition-state ge~metry.~' Cyclopentyne generated by base treatment of dibromomethylenecyclobutane (58) has been found to react stereospecifically with cis-and trans-but-2-ene and on this 46 N.Egger R. Prewo J. H. Bieri L. Hoesch and A. S. Dreiding Helu. Chim. Acta 1983 66 1608. 47 G. B. Blackwell R. N. Haszeldine and D. R. Taylor J. Chem. Soc. Perkin I 1983 1. 48 P. Konig J. Zountsas K. Bleekmann and H. Meier Chem. Ber. 1983 116 3580. 4Y A. Padwa and J. G. MacDonald J. Org. Chem. 1983 48 3189. ''I J. C. Wu J. Mareda Y. N. Gupta and K.N. Houk J. Am. Chem. SOC.,1983 105 6996. C.-Y. Lin. J. Mareda. K. N. Houk and F. R. Frouczek. J. Am. Chem. Soc.. 1983. 105. 6714. Reaction Mechanisms -Part (i) Pericyclic Reactions 0 &o @ /\ / -\ ,H 0 H H C0,Et Et 0,c H (57) (56) w;;=[a] (58) basis has been assumed to have an antisymmetric singlet ground-state. Concerted [T~S+ T~S]cycloaddition is thus allowed as in the case of 1,8-dehydronaphthalene. This highly strained cycloalkyne preferentially adds to one double bond of b~tadiene.~~ 4 Sigmatropic Rearrangements Claisen rearrangement of (59) shows a preference for axial attachment to the ring in the product but relatively minor substitution in the vinyl ether portion of the molecule can alter this preference to eq~atorial.~~ CH,COR R = OEt 87 13 ax :eq TCH2 -QHz Bu' Bu' (59) R = Et OEt OSiBu'Me Control of enolate geometry has been achieved using the allylic glycolate (60) where internal chelation of lithium fixes the double bond configuration Claisen rearrangement occurs with high stereoselectivity (-10 1) to give (61) and (62) from (E) and (2)-substituted (allyl) double bonds re~pectively.~~ 4' C0,Li R~ = H R3 = Me R2 = Me R3 = H (61) OR * R3 (60) '' L.Fitjer and S. Modaressi Tetrahedron Lerr. 1983 24 5495. R. E. Ireland and M. D. Varney J. Org. Chem. 1983 48 1829. s4 J. Kallrnerten and T. J. Could Tetrahedron Lett. 1983 24 5177. R. S. Atkinson 6-Allyloxyindoles appear to undergo highly regioselective Claisen rearrangement (Scheme 9).55 60-70% Scheme 9 It has been suggested that regioselectivity in the trifluoroacetic acid (TFA)-catalysed Claisen rearrangement of ester-substituted allyl phenyl ethers e.g.(63) may be correlated with the response of the chemical shift of the I3Cn.m.r. resonances of the respective ortho-carbons to protonation by TFA the major products are those derived by rearrangement to the (sometimes more sterically hindered) ortho-position whose carbon resonance is shifted downfield the less.56 New [3,3] sigmatropic rearrangements are involved in the formation of reaction products from allyl sulphides and dichlor~ketene~’ (Scheme 10) and in the benzoyla-tion of nitrones (Scheme 1 The overall conversion in the latter case corresponds to a a-benzoyloxylation (hydroxylation) of the aldehyde from which the nitrone was derived.0 I1 Is’ CJ0-Q’ + /\ --.+ 0 C II CI c1 CI cj CI CI 2045% Scheme 10 The impressive potential of the anion-acceleratedClaisen rearrangement is shown by the formation of the highly crowded product (64) on heating the sodium salt of N-methoxycarbonylhydrazone (65). Heating the corresponding cyclohexane-I ,2-dione (66)brings about a rare reverse Claisen rearrangement the driving force for which must be the steric crowding present.59 55 C. J. Moody J. Chem. SOC.,Chem. Commun. 1983 1129. 56 L. M. Harwood J. Chem. SOC.,Commun. 1983 530. 57 R. Malherbe G. Rist and D. Bellus J. Org. Chem. 1983 48 860. 58 C. H. Cummins and R.M. Coates J. Org. Chem. 1983 48 2070. 5Y A. A. Ponaras J. Org. Chem.. 1983. 48 3866. Reaction Mechanisms -Part (i) Pericyclic Reactions J H' R 0 ? '0 e-H Scheme 11 Me Me Me Me 115°C' --+ x Q: N- N'I / (65) (64) (85%) Me Me Me Me 0' Me Among new [2,3]sigmatropic rearrangements6' is the oxidation of allylic iodides to allylic alcohols (with rearrangement) which has been shown to follow the pathway indicated in Scheme 12.6' It has been claimed that the method is comparable in yield to that obtained in allylic sulphoxide -sulphenate ester (followed by phos- phine scavenging of the latter) for effecting allylic alcohol rearrangement but has the advantage that no heating is required. (It is also subject to the availability of the required iodide.) Scheme 12 hO Review K.Hiroi and S. Sato Annu. Rep. Tohuku Coll. Pharm. 1982 (29) 1-37. '' S. Yamamoto. H. ltani T. Tsuji and W. Nagata J. Am. Chem. Soc. 1983 105 2908. R. S. Atkinson The ally1 selenoxide selenenate equilibrium (Scheme 13) lies more on the side of the ester than in the corresponding sulphoxide S sulphenate ester because of (a) the weaker Se-C bond strength compared to S-C and (b) the smaller degree of multiple bonding in Se=O by comparison with S=O." Y = SorSe Scheme 13 The [2,3] sigmatropic rearrangement has in general exhibited only moderate levels of diastereoselection by comparison with the [3,3]sigmatropic rearrangement. Attempts have been made using the [2,3] Wittig rearrangement (Scheme 14) to H Me -\ Jh 1 I R "? -H 0-Scheme 14 examine the changes in stereoselectivity with changes in substitution.To accommo-date the effects observed the authors propose a transition-state geometry (67) [rather than the more usually assumed envelope (68)] in which repulsion between R and the olefin H is the major factor determining stereoselectivity. A gauche relationship between R and R' or R3 explains why the stereoselectivity is little affected by the nature of R2(R3) (whether an alkyl group or hydr~gen).~~ (67) (68) Two examples of [2,3]sigmatropic rearrangement which do show high stereoselec- tivity are the conversion of the individual ally1 sulphoxides (69) and (70) into (71) and (72) respectively [for which a transition state corresponding to (73) is assumed with a methyl group preferring the 'equatorial' position]64 and rearrangement of the 62 H.J. Reich K. E. Yelm and S. Wollowitz J. Am. Chem. SOC.,1983 105 2503. 63 K. Mikami Y. Kimura N. Kishi and T. Nakai J. Org. Chem. 1983 48 279. 64 R. S. Garigipati and S. M. Weinreb J. Am. Chem. SOC..1983 105. 4499. Reaction Mechanisms -Part (i) Pericyclic Reactions OH J P(OMe) + HCO CH Ph csc-vr NHC02CH2Ph R' R2' Rl (69) R' = Me R' = H (71) R' = Me,R' = H (70) R' = H,R2 = Me (72) R1 = H,R2 = Me N HC0,CH ,Ph allylic sulphinate (74) to the sulphone (75) in which chirality at sulphur is efficiently transferred to carbon.65 A dramatic solvent-effect in the latter reaction using dimethylformamide remains to be explained.8- Ar-S-0 R' ,\ I CH2 -ArS02CCH=CH2 I .. R12 R2 R2 (75) (74) R' R' = H Me or (CH,),Me Other sigmatropic rearrangements include the circumambulation of the (sub- stituted) bridging carbon in e.g. (76) which proceeds at 0°C with inversion at the migrating group in agreement with orbital symmetry control. The low activation- barrier is attributed to the high ground-state enthalpy of the bicyclopentene.66 Heating (78) results in formation of (77). This is viewed by the authors as a concerted [1,5] hydrogen-shift within the dipolar resonance structure followed by ring-closure. However 1,Shydride shift in this system also explains the effects of changes in R and also that the reaction fails with CH3 instead of CF3.Distinction between these two routes is a fine but real one particularly in terms of the geometries involved." A [1,5] sigmatropic rearrangement of the nitro group in the ipso-nitration product (79) occurs and there is good evidence that this is concerted.68 6S K. Hiroi R. Kitayama and S. Sato J. Chem. SOC.,Chem. Commun. 1983 1470. 66 F.-G. Klarner and F. Adamsky Chem. Ber. 1983 116 299. 67 W. Verboom B. G. VanDijk and D. N. Reinhoudt Tetrahedron Lett. 1983 24 3923. 6X G. S. Bapat. A. Fischer. G. N. Hendersen and S. Raymahasay. J. Chem. Soc.. Chem. Commun. 1983 119. R. S. Atkinson MeFf MeFf B;02 __* O;BMe R (79) R = H (95%) The cyclononatetraene ring in (80) has a pronounced helicity (X-ray) which results in diastereotopic hydrogens within the methylene group.Heating at 100 "C results in an unusual [1,5] vinyl shift to give (81).69 A -w I00 "C \/ Ph Ph An ab initio calculation of the preferred transition-state for [1,5] sigmatropic rearrangement of hydrogen in cis-1,3-pentadiene does not support the conclusion (drawn recently from the temperature dependence of the kinetic isotope effect) that transfer of hydrogen takes place via a linear (CIv) (82) rather than an envelope (C,) (83) geometry." n (82) (83) A detailed study of the Stevens rearrangement of acyl-stabilized ammonium ylides e.g. (84) to (85) has revealed some surprising results including the finding that in water at O'C rearrangement of the salt (84) is essentially intramolecular with 69 A.G. Anastassiou H. S. Kasrnai and M. Sabahi Helu. Chim. Acta 1983 66,718. 70 B. A. Hess and L.J. Shaad. J. Am. Chern. SOC.,1983 105 7185. Reaction Mechanisms -Part ( i) Pericyclic Reactions 65 almost complete retention of configuration in the migrating group. Nevertheless the rearrangement is believed to be proceeding uia a non-concerted (biradical) route based on the decrease in intramolecularity and stereospecificity of the reaction with decrease in solvent viscosity." 5 Other Pericyclic Reactions Introduction of an ester group on the carbon of the N-acylimine precursor (86) facilitates the (retro-ene) removal of acetic acid as shown by a lowering of the reaction temperature required by 200 "C the superior yield of product is attributed to enhanced enophilic character (lower energy LUMO) in the C=N of (87).72 __* 0-I NOCOMe -+ [?HI CH,R CH,R R = H (40%) (86) (87) R = CO,Et (100%) High asymmetric induction has been obtained in the stannic chloride catalysed ene reaction of chiral a-ketoester (88) with hex- 1-ene.73 RO%:r __* HO+Zr Me O<--78 -L-111 diastereoisomer excess > 90% I Me (88) Cleavage of the individual cyclic sulpliinamides (89) and (90) with base is accom- panied by stereospecific retro-ene elimination of sulphur dioxide the chirality at C" in (90) and (92) is presumed to be determined by the preference of the methyl group for the equatorial position in a chair-type transition state (93).74 Me Me R' R 'R (89) R = H R1= Me b (91) R = H R1= Me (85%) (90) R = Me R' = H + (92) R = Me R' = H(83%) w.D. Ollis M. Rey and I. 0. Sutherland J. Chem. SOC. Perkin Trans. I 1983 1009. 71 K. Koch J.-M. Lin and F. W. Fowler Tefruhedron Leff. 1983 24 1581. 73 J. K. Whitesell D. Deyo and A. Bhattacharya J. Chem. SOC.,Chem. Commun. 1983 802. 71 R. S. Garigipati J. A. Morton and S. M. Weinreb. Tetrahedron Lett.. 1983. 24 987. R. S. Atkinson Me Elimination of tropolone from the ether (94) proceeds with high stereoselectivity with elimination of the hydrogen trans to the ether oxygen as shown by deuterium labelling and mass spectral data. It has been suggested that this is a concerted [7r2s + a2s + a2a]reaction but it is difficult to visualize (by drawing or models) the transition state which leads preferentially to trans elimination.The authors do not appear to have completely eliminated the possibility that the reaction is a trans elimination with the solvent (DMSO) acting as the base." D (94) H. Takeshita and Mametsuka J. Chern. Soc. Chern. Cornrnun. 1983 483.