4 Reaction Mechanisms Part (i)Pericyclic Reactions By R. S. ATKINSON Department of Chemistry University of Leicester Leicester LE1 7RH 1 General A monograph on natural product synthesis using pericyclic reactions has appeared.' A computer-assisted procedure has been devised to treat competitive thermal pericyclic reactiom2 2 Electrocyclic Reactions A remarkable stereospecificity has been demonstrated in the thermal conrotatory ring-opening of the trans-substituted cyclobutene (1) to the 2,Z-substituted butadiene (2).3This conclusion was arrived at by a study of the equilibria in Scheme 1. It has previously been assumed that such substituted cyclobutenes always preferen- tially ring-open to E,E-butadienes (3) to minimize repulsive steric effects. A survey of a number of substituted cyclobutenes has shown that this aberrant behaviour is not restricted to trifluoromethyl groups as substituents but is also exhibited to a lesser degree by other substituents which are not electron donating.A rationalization of the results in molecular orbital terms has been offered? F a F F 3 c'F E E Scheme 1 (3) ' 'Natural Products Synthesis through Pericyclic Reactions' ed. G. Desimoni G. Tacconi A. Barco and G. P. Pollini ACS Monograph No. 180 1983. * J. S. Burnier and W. L. Jorgensen J. Org. Chem. 1984,49 3001. W. R. Dolbier H. Koroniak D. J. Burton A. R. Bailey G. S. Shaw and S. W. Hansen J. Am. Chem. Soc. 1984 106 1871. W. Kirmse N. G. Rondan and K. N. Houk J. Am. Chem. Soc. 1984 106 7989. 27 R.S. Atkinson Dissymmetric cis-1,4-disubstituted cyclobutenes in which the substituents are very similar can nevertheless be coaxed into selecting one of the two possible conrotatory ring-openings preferentially. In model studies towards the synthesis of verrucarin A conrotatory ring-opening of the cyclobutene (4) gave the dienes (5) and (6) in a 2 :1 ratio with the major isomer having the required stereochemistry of verrucarin.' Electrochemically induced electrocyclization of (7) via a radical anion has been shown to proceed in a conrotatory fashion and the product (8) is identical with the photolysis product of (7). The nodal character of the highest occupied molecular orbital is presumably the same in both ground-state radical-anion and neutral photoexcited state.6 A cascade of four consecutive pericyclic reactions is involved in the reaction of alkynes and cyclobutenones to give (polysubstituted) aromatics (Scheme 2).This annulation method has been used to synthesize the antifungal antibiotic DB-2073 (9h7 R' R' R' R4 IX R4 R3 2. 2si 2s X R3 R2 R3 1;a:;;e2m Scheme 2 B. M. Trost and P. G. McDougal J. Org. Chem. 1984 49 458. M. A. Fox and J. R. Hurst J. Am. Chem. Soc. 1984 106 7626. ' R. Danheiser and S. K. Gee J. Org. Chem. 1984 49 1672. Reaction Mechanisms -Part (i) Pericyclic Reactions > -Ll;ic<. i;r. 61r + 47~ @ -~ / 41r + 677 \ ~ 1 H [1,5] sig. rearr. 3 Cycloaddition Reactions A number of reviews on aspects of the Diels-Alder reaction have appeared this year including recent advances and synthetic applications of the intramolecular Diels- Alder ;lo reactivity of exocyclic dienes tetraenes and hexaenes ;ll asymmetric Diels- Alder (and ene) reactions ;12-14 and theoretical considerations of regio- and stereo-~electivity.’~ Acetylene equivalents in cycloaddition reactions have been reviewedI6 and many anthracyclinone syntheses include different Diels- Alder reac- tion~.‘~ Aspects of the mechanism of the Diels-Alder have aroused some controversy.Dewar et al. adopt a fundamentalist position with regard to the concertedness of pericyclic reactions and in particular to whether both new C-C bonds in this reaction are formed synchronously.’8 Their conclusion is that all the experimental evidence can be interpreted in terms of formation of one of these bonds being almost complete while the other is very incomplete.A probe for the symmetry of the transition state of this reaction has used chiral prosthetic groups at the termini of the dienophile and an examination of co-operativity in asymmetric induction on addition to a two-fold symmetric diene.” The enantiomeric ratio produced when a dienophile containing two independent chiral moieties (e.g. dibornyl fumarate) reacts with anthracene is found to be the square of the ratio obtained when the dienophile contains only one of the chiral moieties (e.g. bornyl methyl fumarate) and therefore the C-C bond formations are adjudged to be synchronous. (Dewar has an interpretation of these results which ’A.Beck L. Knothe D. Hunkler and H. Prinzbach Tetrahedron Lett. 1984 25 1785. J. Breulet and H. F. Shaefer J. Am. Chem. Soc. 1984 106 1221. 10 A. G. Fallis Can. J. Chem. 1984 62 183. P. Vogel Methods Stereochem. Anal. 1983 3 147. W. Oppolzer Angew. Chem. Int. Ed. Engl. 1984 23 876. l3 L. A. Paquette in ‘Asymmetric Synthesis,’ vol. 3 ed. J. D. Morrison Academic Press Orlando Florida 1984 pp. 455-501. l4 P. Welzel Nachr. Chem. Tech. Lab. 1983 31 979. 15 R. Gleiter and M. C. Boehm Methods Stereochem. Anal. 1983 3 105. 16 0. DeLucci and G. Modena Tetrahedron 1984,40,2585; see also 0. DeLucci V. Lucchini L. Pasquato and G. Modena J. Org. Chem. 1984,49 596. 17 T. R. Kelly Tetrahedron 1984 40,4537 et seq. 18 M. J. S. Dewar and A.B. Pierini J. Am. Chem. Soc. 1984 106 203 209. 19 L. M. Tolbert and M. B. Ali J. Am. Chem. Soc. 1984 106 3806; see also R. GrCe M. Laabassi P. Mosset and R. Carrie Tetrahedron Lett. 1984 25 3693. 30 R. S. Atkinson supports his position.) The co-operativity in this reaction vanishes when Lewis acid catalysis is applied and an asymmetric transitiomstate is presumed to obtain in this case. Ab initio (STO-3G basis set) calculations for the Diels-Alder reaction suggest that a symmetrical transition-state structure exists.20 Reaction of unsymmetrically substituted tropones and dienes (Scheme 3) are ,6 + ,4 cycloadditions which are highly regioselective and exo-stereoselective. Clearly therefore the recent suggestion of Alston et al. -that in some Diels-Alder reactions secondary frontier molecular orbital (FMO) interactions control regioselectivity rather than primary FMO interactions -cannot apply to these ,6 + ,4 cycloadditions.To go on to conclude however as the authors do that secondary FMO interactions are unlikely to control regioselectivity in Diels- Alder reactions either seems unwarranted in the view of the present author.21 4-\ \ &Q gd B Scheme 3 Considerable effort continues to be expended on the synthesis and study of dienophiles bearing chiral auxiliaries with a view to maximizing the diastereoisomeric purity of the Diels-Alder adduct. Dienophiles which have been employed successfully for this purpose include (12),22(13),23 and (14)24,25 and cyclopentadiene invariably seems to be the 'test' diene used.An X-ray structure determination on (14) shows that the environment of the acrylate double bond makes its facial selectivity explicable. 0-\\ Co2Me 7% [aID-15" 93% [a]D-0.6" Et02C oq0 Me+ -I TiCI4 -63°C H 0 HO (13) 93:7 d.e. 32 1 endolexo 2o F. K. Brown and K. N. Houk Tetrahedron Lett. 1984 25 4609. 21 M. E. Garst V. A. Roberts K. N. Houk and N. G. Rondan J. Am.Chem. SOC.,1984 106 3882. 22 C. Maignan A. Guessous and F. Rouessac Tetrahedron Lett. 1984 25 1727. 23 T. Poll G. Helmchen and B. Bauer Tetrahedron Lett. 1984 25 2191. 24 W. Oppolzer C. Chapuis and G. Bernardinelli Tetrahedron Lett. 1984 25 5885. 25 W. Oppolzer M. J. Kelly and G. Bernardinelli Tetrahedron Lett. 1984 25 5889.Reaction Mechanisms -Part (i) Pericyclic Reactions 31 (14) R = cyclohexyl Addition of the p-tolylsulphinylacrylate(15)to cyclopentadiene gave (16) as the major diastereoisomer whose absolute configuration was determined by correlation with (+)-2-endo-methyl-2-exa-norbornanecarboxylic acid.26 It is argued that the absolute configuration of the major product is inconsistent with an s-cis-conformation of the S-0 and C=C bonds for the acrylate in the Diels- Alder transition-state. The preferential endo-overlap of the sulphinyl (and Me) group over the ethoxycarbonyl group is however noteworthy. + I '* (15) (16) 63% Ho2cb Me Aldehydes are increasingly seeing use as 27r-components in Diels- Alder additions usually catalysed by Eu(fod) but also accelerated by high pressure e.g.(17)+ ( 18).27The absolute configuration of (18)was proved by chemical correlation. Et ?Me FHO H+OH \ -20 kbar 53 "C,20 h High threo-selectivity (60 1) is observed in the formation of (19).The sense and efficiency of diastereoselection in these ,4 + ,2 reactions is sensitive both to the Lewis acid catalyst and to the substitution pattern of the diene chelation-controlled addition (20)may be important in some cases; in others the bulky solvated metal-ion may prefer the less hindered exo-site (21).28 26 T. Koizumi I. Hakamada and E. Yoshii Tetrahedron Lett. 1984 25 87. 27 J. Jurczak T. Bauer and S. Jarosz Tetrahedron Lett. 1984 25 4809. 28 M. M. Midland and R. S. Graham J.Am. Chem. SOC.,1984 106,4294; see also S. Danishefsky W. H. Pearson and D. F. Harvey ibid. 1984 106 2455 2456; S. Danishefsky and M. Bednarski Tetrahedron Lett. 1984 25 721; S. Danishefsky and R. R. Webb J. Org. Chem. 1984 49 1955. R. S. Atkinson OSiMe 0 A number of examples of Diels-Alder reactions in which cation radicals are proposed intermediates have been reported re~ently,*~,~~ but attention has been drawn to the possibility of these reactions in some cases being acid-catalysed as a result of the aminium cation radical-initiator generating a proton source.31 An Fe"'-doped montmorillonite or bentonite clay has been found to accelerate the rate of Diels- Alder reaction of furan with ap-unsaturated carbonyl compounds32 and the dimerization of cycl~hexadiene.~~ Diels- Alder reaction of cyclohexadiene with the enantiomerically pure a-chloronitroso compounds (22)33and (23)34 gave the corresponding enantiomeric bicyclic oxazines in high enantiomeric purity as shown by their specific rotations and by the n.m.r.spectra of the corresponding 10-camphorsulphonyl derivatives. -20 "C 69% 3 95% e.e. 69% 3 95% e.e. Dialkyldiimides do not undergo Diels- Alder addition to dienes the retro-Diels- Alder is almost invariably thermodynamically preferred. Protonation of the bicyclic azo compound (24) however renders it dienophilic as exemplified by cycloaddition 29 R. A. Pabon D. J. Bellville and N. L. Bauld J. Am. Chem. SOC. 1984 106 2730 and refs. therein. 30 P. Laszlo and J. Lucchetti Tetrahedron Lett.1984 25 1567. 31 P. G. Gassman and D. A. Singleton J. Am. Chem. SOC.,1984 106 6085 7993. 32 P. Laszlo and J. Lucchetti Tetrahedron Lett. 1984 4387 2147. 33 M. Sabuni G. Kresze and H. Braun Tetrahedron Lett. 1984 25 5377. 34 H. Felber G. Kresze H. Braun and A. Vasella Tetrahedron Lett. 1984 5381. Reaction Mechanisms -Part (i) Pericyclic Reactions to cyclohexadiene. Reversal of the thermodynamic equilibrium in this cycloaddition in the presence of acid is attributed to the conversion of the weakly basic (but protonated) azo function into the more basic hydra~ine.~~ Deprotonation of (25) gives the free base which undergoes a retro-Diels-Alder reaction at room temperature (?+CQ. 7h). Another unusual dienophile is singlet sulphur IS2 which is apparently generated when the trisulphides (26) are treated with Ph3PBr2 a reaction in which the sulphur analogue of phosphine ozonide Ph3PS3 is a presumed intermediate.In the presence of conjugated dienes the singlet sulphur is trapped but unlike singlet oxygen it appears to show no 2.rr + 27r or enophilic activity.36 CH-Cl. R3MSSSMR3+ Ph,PBr2-L' 2R,MBr + [Ph3PS3] -S2 + Ph,P=S 25 "C (26) A number of interesting and potentially useful dienes have been synthesized including (27),37(28),38(29),39 and (30).40The trimethylstannyl group in (27) can be further substituted by electrophiles if the X group is base stable. Me3Sn HsnMe3 1. MeLi SnMe3 E = SiMe, SPh C1 SnMe, CH2SiMe3 C(OH)R2 (27) R4yCHo R3 R'O R3 &R4 R3 = H alkyl (28) 35 S.F. Nelson S. C. Blackstock and T. B. Frigo 1 Am. Chem. SOC.,1984 106 3366. 36 K. Steliou Y. Gareau and D. N. Harpp J. Am. Chem. SOC.,1984 106 799. 37 H. J. Reich K. E. Yelm and I. L. Reich 1. Org. Chem 1984 49 3438. 38 J. I. Luengo and M. Koreeda Tetrahedron Lett. 1984 25 4881. 39 W. A. Nugent and J. Calabrese J. Am. Chem. SOC.,1984 106,6422. 40 Y. Eta H. Yasuda 0.Tamura and Y. Tamura Tetrahedron Lett. 1984 25 1813. R S. Atkinson R' Ti catalyst R' R2=alkyl Ph,OEt R'C C(CH2) C CR2 -Me Me \/ RZ (29) Unlike the corresponding 5-methoxycarbonylcyclopentadiene,the 5-ferrocenyl- substituted cyclopentadiene (3 1) can be obtained isomerically pure. Reaction with activated dienophiles followed by ferrocenyl +methoxycarbonyl interconversion gave (32) and thus (31) is in practice a substitute for 5-methoxycarbonylcyclopen-tadie~~e.~* Me0,C H v Fp =T~-C,H,F~(CO)~ A useful addition to the Danishefsky suite of dienes is the l-t-butoxy-3-[(trimethyl-sily1)oxylbutadiene (33) which has been synthesized in 50 g quantities.Diels- Alder adducts of this diene with electron-poor alkenes as dienophiles can be converted into 3-t-butoxycyclohexanones (34) without enone formation.42 OBu' OBu' OBu' (33) (34) The Bradsher-Falck version of the inverse Diels-Alder reaction -the use of isoquinolinium salts as dienes with electron-rich dienophiles -has been cleverly extended to the synthesis of C-naphthylglycosides by using cyclic enol ethers (glycals) as dienophiles (Scheme 4).43 The formal ,4 +,4 and ,4 +,2 adducts of benzene and anthracene (35) and (36) respectively have been synthesized.Their thermodynamic parameters for thermal decomposition and quantum yields in photochemical decomposition have been interpreted as evidence for orbital-symmetry control in both ground-state and excited-state reactions.@ 41 M. E. Wright J. F. Hoover G. 0. Nelson C. P. Scott and R. S. Glass J. Org. Chem. 1984 49 3059. 42 R. P. Potman N. J. M. L. Janssen J. W. Scheeren and R. J. F. Nivard J. Org. Chem. 1984,49 3628. 43 R. W. Franck and R. B. Gupta J. Chem. Soc. Chem. Commun. 1984 761. N. C. Yang M.-J. Chen and P. Chen J. Am. Chem. Soc. 1984 106 7310. Reaction Mechanisms -Part (i) Pericyclic Reactions CHO H+/H,O / OH Scheme 4 Thermal stabilities of (37) and (38) were examined to test for the facility of retro-Diels-Alder fragmentation.At 160 "C(37) was stable over 90 h whereas (38) fragmented smoothly at 95 "C with first-order kinetics (k= 1.67 x lop4s-'). It would be anticipated that (38) be less stable than (37) if the fragmentation is concerted and naphthalene resonance energy contributes to a lowering of the transition-state energy. That (38) does not spontaneously disintegrate at room temperature can be attributed to the significant barrier required for deformation from its preferred conformation (39) (or its mirror image) to the conformation required for concerted fragmentati~n.~' L. A. Paquette H. Jendralla and G. Lelucca J.Am. Chem. SOC.,1984 106 1518. R. S. Atkinson 4 1,3-Dipolar Cycloadditions A treatise on 1,3-dipolar cycloaddition reactions (in two volumes) has been pub- lis hed.46 Aromatic diazonium salts as well as reacting concertedly with diene~,~' show dipolarophilic activity with e.g. azomethine ylides and thiocarbonyl ylides leading to triazolium salts (40) and thiadiazolines (41) re~pectively.~~ Me N PhfiPh $iy ArN ph + BF Arf;12BF B F4 (40) 47% Ar = p-N02C& BiphC CH S Biphc ) +Biph( S149% ArN'N ArN-N Biph = BF4 (41) 49% Hunig et al. have observed some unusual intramolecular 1,3-dipolar cycloaddition reactions in systems49 having C=C and 1,3-dipole in enforced proximity. Thus the azoxy compounds (42) readily undergo thermal or acid-catalysed cycloaddition to form unusually stable 1,2,3-oxadiazolidines ;" previous azoxy 1,3-dipole and alkene cycloadditions have led to ring-opened products from these oxadiazolidines.Methyl- ation of (43) does not give the expected quaternary salts (44) but pyrazolidinium salts (45).51 The authors suggest that a 1,3-dipolar addition is involved here also 0-Me \ (43) (44) 46 '1,3-Dipolar Cycloaddition Chemistry,' ed. A. Padwa Wiley New York N.Y. 1984. 47 F. Bronberger and R. Huisgen Tetrahedron Lett. 1984 25 57. 48 F. Bronberger and R. Huisgen Tetrahedron Lett. 1984 25 65. 49 K. Beck A. Hohn S. Hunig F. Prokschy Chem. Ber. 1984 117 517; S. Hunig and F. Prokschy ibid. 1984 117 534. so S. Hunig and M.Schmitt Tetrahedron Lett.1984 25 1725. 51 S. Hunig and F. Prokschy Chern. Ber. 1984 117 2099. 37 Reaction Mechanisms -Part (i) Pericyclic Reactions and presume that deprotonation of the methyl group is dramatically enhanced by the presence of the neighbouring double bond [in its absence no H-D exchange in the (normal) quaternary salt occurs in the presence of D+-MeOD]. How the double bond brings about this dramatic enhancement of acidity of the methyl group is not clear. Decarboxylative transamination of a-amino-acids has been assumed to proceed via the concerted process (46) += (47). Evidence for an alternative mechanism which involves decarboxylation via the zwitterionic form (48) is the trapping of the latter by 1,3-dipolarophiles (Scheme 5).52 This trapping procedure has also been accomplished intramolecularly e.g.Scheme 6. Ph R2 R’ R2 Scheme 5 H CHO DMF A do ____* 2L \/ 58% Scheme 6 A study of stereoselectivity in nitrile oxide addition to a variety of chiral allylic ethers (49) has led to a proposal for the preferred transition-state geometry shown in (50).s3 In this geometry the alkoxy function occupies an ‘inside’ site and the alkyl substituent the sterically less-crowded anti-position. It is believed that the wbond becomes electron-deficient in the transition state and consequently is stabil- ized by the electron-donating effect of CT~-~-T overlap and least destabilized by UT.-~-V interaction when the latter is in the inside position close to the plane of the wbond.52 R. Grigg and S. Thianpatanagul J. Chem. SOC.,Chem. Commun. 1984 180; see also R. Grigg F. M. Aly V. Sridharan and S. Thianpatanagul ibid. 1984 182. 53 K. N. Houk S. R. Moses Y.-D. Wu N. G. Rondan V. Jager R. Schohe and F. R. Fronczek J. Am. Chem. SOC.,1984 106 3880. R. S. Atkinson OR V (49) erythro OR' threo anti (50) The proposal above is in contrast to that of Kozikowski and Gho~h~~ who envisage that the allylic oxygen is aligned anti to the developing C-0 bond in the transition state. A variety of 1,3-dipoles have been reacted with phosphaethyne (51) regiospecifi- cally to give phosphorus-containing heterocycles e.g. (52).5' Bu'C=P + PhN -PhN I 52% 'p5CBu' (51) (52) 5 Cheletropic Addition and Elimination The ,4 + "2 addition of free germylenes Me,Ge to 1,3-dienes (Scheme 7) has been shown to proceed faster with more electron-deficient dienes suggesting that the reaction is LUMOdiene-HOMOgermylene ~ontrolled.'~ Me Me , 70"C d M; he Scheme 7 Similarly 1 -stannacyclopent-3-enes are now readily available by addition of stannylenes R,Sn (including SnCl, SnBr, and SnI,) to 1,3-dienes.Judging from the stereospecificity of the reaction a ,4 + ,2 addition is operating here also and the yields with various substituted dienes suggest that a LUMOdie,e-HOMO,t,n,ylene is likewise of major irnp~rtance.~' Acyl- and sulphonyl-thionitroso compounds have been obtained by extrusion from the intermediate ylides themselves obtained by Diels- Alder addition of thiophene S-N ylides to dienophiles (Scheme 8).These reactive thionitroso 54 A. P.Kozikowski and A. K. Ghosh J. Org. Chem. 1984,49,2762. 55 Y.Y.C. Yeung Lam KO R. Came A. Muench and G. Becker J. Chem SOC.,Chem. Commun. 1984 1634; W. Rosch and M. Regitz Angew. Chem lnt. Ed. Engl 1984 23 900; see also A. Schmidpeter and A. Willhalm ibid 1984 23 901. 56 J. Kocher and W. P. Neumann J. Am. Chem SOC 1984 106 3861. 57 R. Marx W. P. Neumann and K. Hillner Tetrahedron Lett. 1984 25,625. Reaction Mechanisms -Part ( i) Pericyclic Reactions cyl CI’ ‘Cl + (’I -CI&R:\ +S-NR -CI R’ CI R’ c$: CI -NR CI 1 +R-N=S Scheme 8 compounds are trapped non-periselectively giving both 47r + 27r cycloaddition and ene reactions.’* Di-iminosuccinonitrile (DISN) (53) is prepared by base-catalysed addition of HCN to cyanogen and is a versatile polyfunctional reagent whose heterodiene unit HN=C-C=NH undergoes apparent 47r + 27r cycloaddition with electron-rich alkenes e.g.dimethoxyethene (Scheme 9). H -NcaI Nc@(NH +MeOCH=CHOMe OMe H+ NC[) ~ OMe orA NC HN CN NC (53) 76% it NcgH R = R’ = OMe I N [ 1,4] sig. rearr. ** C NH CH,CN + -H wcN HY CN R R’ A R R’ \ (55) R = Ph NcgNH2 R‘= H 58% P Ph (54) Scheme 9 Intriguingly however styrene yields aziridine (54) as the only isolable product with DISN. It is suggested that DISN reacting via its latent nitrenium resonance hybrid in a ,2 + ,2 cycloaddition to the alkene gives the aziridinium ion (55) which is the intermediate in formation of both aziridines and dihydropyridazines.This mechanism avoids the necessity for the cisoid-form of DISN to be invoked 0. Meth-Cohn and G. van Vuuren J. Chem. SOC.,Chem. Commun. 1984 1144. R. S. Atkinson but it does require C(CN)-=C(CN) bond rotation within the anionic portion of (55) before sigmatropic rearrangement is p~ssible.’~ Thermal cheletropic elimination from the iminonaphthalene (56) generates the arylsulphenylnitrene which has been trapped by alkenes to give aziridines in good yields.60 SAr 6 Sigmatropic Rearrangements Recent reviews in this area include those on mercury and palladium catalysed [3,3] sigmatropic rearrangements,61 chirality transfer uia sigmatropic rearrangements,62 and walk rearrangements in [n.1.O]bicyclic corn pound^.^^ Striking contrasts have been found in the stereoselectivities of Claisen rearrange- ments of pyranoside and carbocyclic ally1 vinyl ethers.Thus in contrast to the Claisen rearrangement of (57) which gives a 48% and 52% yield of (58) and (59) respectively rearrangement of e.g. (60) and (61) gave the corresponding aldehydes /CO,Et PhCN phTc%‘ phq;% ___) OHC 0 OMe I+‘/OMe -Si Si 59 T. Fukunaga and R. W. Begland J. Org. Chem. 1984,49 813. 60 R. S. Atkinson M.Lee and J. R. Malpass J Chem. SOC.,Chem. Commun. 1984 919. 61 L. E. Overman Angew. Chem. Int. Ed. Engl. 1984 23 579. 62 R. K. Hill in ‘Asymmetric Synthesis’ vol. 3 ed. J. D. Morrison Academic Press Orlando Florida 1984 pp.503-572. 63 F. G. Klaerner Top. Stereochem. 1984. 15. 1. Reaction Mechanisms -Part ( i) Pericyclic Reactions 41 stereospecifically. The anomeric oxygen does not appear to play an important role in determining its stereoselectivity and neither does the trans-ring fusion.@ Claisen rearrangement of the chiral alcohol (62) gave (63) (E:Z = 83 17). Both these stereoisomers were converted into the same enantiomer of the alcohol (64) by cyclization with Tic&. This is taken to mean that chiral transfer proceeds 100% efficiently with the (R)-configuration in (62) yielding (RE)-and (S,Z)-(63) followed by anti-attack in the SE2’-type cyclization of both these stereoisomers to (64).65 +he ,J OHC Y TiCI “‘‘0 100% HO’ (64) Diastereoselection has also been studied in the chelation-controlled ,reland- Claisen rearrangement of (65).Formation of the major diastereoisomer is rational- ized by assuming an anti-relationship of the newly formed C-C bond and the allylic alkoxyl function in a chair transition-state.66 A (major product) This transfer of chirality in the Claisen rearrangement is only possible using secondary (as in the cases above) or tertiary alcohols. The a-silylcrotyl alcohol (66) has been synthesized and resolved and the propionate esters of the enantiomers subjected to Claisen rearrangement uia the ester enolates (Scheme 10).The configur- ation of the enolate double bond generated can be controlled by the choice of base used and the overall transformation here after removal of the silicon is chirality- transfer in the Claisen rearrangement using a chiral primary alcohol eq~ivalent.~’ 64 D.B. Tulshian R. Tseng and B. Fraser-Reid J. Org. Chem. 1984 49 2347; B. Fraser-Reid D. B. Tulshian R. Tseng D. Lowe and V. G. S. Box Tetrahedron Lett. 1984 25 4579. 65 K. Mikami T. Maeda N. Kishi and T. Nakai Tetrahedron Lett. 1984 25 5151. 66 J. K. Cha and S. C. Lewis Tetrahedron Lett. 1984 25 5263. 67 R. E. Ireland and M. D. Varney J. Am. Chem. Soc. 1984 106 3668. R. S. Atkinson (66) \iii iv vii viii ix. x HO,C BzO-/-> vii viii ix x Ho2Cyii+ BzO7 I Me Me 93:7 Reagents i 1.5 eq. Bu'Li-TMEDA; ii MeC02H-THF -78°C; iii resolve; iv EtCOCI-pyr; v (Me,Si),NLi-THF -78 "C; vi TBSiCI -78 "C;vii CH,N,; viii LAH; ix PhCH,Br KH THF; x 50% HBF, MeCN; xi LDA Scheme 10 Claisen rearrangement of 2-morpholino-substituted allyl vinyl ethers (67) proceeds at a rate estimated to be several thousand times faster than for allyl vinyl ether itself (the rate acceleration is significantly affected by the nature of the amine).68 In contrast P-furfuryloxyenamines (68) are transformed into products (69) apparently by [1,3]sigmatropy.It would be of interest to know what part if any radicals play in both these rearrangements since the 2-aminovinyloxy radical (70) is capto-dative stabilized. The facility with which anionic Claisen rearrangement of the vinyl ethers (71) occurs to produce two vicinal chiral centres in (72) is attributed to the drop of ca.10 pK units between (71) and the product.69 68 J. Barluenga F. Aznar R. Liz and M. Bayod 1. Chem. SOC.,Chem. Commun. 1984 1427. 69 S. E. Denmark and M. A. Harmata Tetrahedron Lett. 1984 25 1543. 43 Reaction Mechanisms -Part (i) Pericyclic Reactions p-TolSO 1 ~ , KH-THF so' R'~ \ o~RLiCH,SOCH R2 'n P' n R' M&,* 4 +G-CO,Bu' -M%5 -i/ Bu'0,C C02Bu' R' R2 (75) (73) (74) ha-Claisen rearrangement of (73) + (74) has been shown to depend critically on the purity of the t-butyl propiolate used for formation of (73) from the amine (75)?* The Carroll rearrangement (Scheme 11) like many other [3,3] sigmatropic rear- rangements has been found to be dramatically accelerated by base.-M Me& er -Meno ,O -00 OH H' Scheme 11 Thus whereas this thermal rearrangement is usually carried out at 13O-22O0C the dianions of allylic acetoacetates rearrange at room temperature or in refluxing THF (Scheme 12) the mono-anion is unreactive to boiling in THFfor several hours. The acetoacetates were obtained in good yield and purity by treatment of the ally1 "+SiMe3 2:%. Me iMe3*oc Me-o 0 0 0 iMe, R' = Me R' = H 84% R' = H,R' = Me 40% Me 0 Scheme 12 S. Chao F. A. Kunng J.-M. Gu H. L. Ammon and P. S. Mariano J. 01%Chem. 1984,49 2708. R S. Atkinson alcohol in ether at -20°C with diketene and a catalytic amount of 4-dimethyl- amin~pyridine.~' Cope rearrangement of (76) has been shown to proceed in the gas phase using ion cyclotron resonance spectrometry for the case where R = Me.The secondary alcohol (R = H) is slower to react. Since a similar rate difference is observed in THF or DMSO the effect is unlikely to be the result of differential ion-pairing or solvation An ab initio calculation for the transition state of the Cope rearrangement (using a 3-21G multiconfiguration SCF wave function) suggests that bond making and bond breaking occur in unison,73 contradicting Dewar's general assertion18 that multibond reactions are not synchronous. Other theoretical studies (of substituent effects on the rate) of the Cope and Claisen rearrangements have appeared.74 Diastereoselectivity at an increasingly high level is being accomplished in [2,3]- sigmatropic rearrangements also.Thus Wittig rearrangement of (77)bearing the 'Meyers' chiral oxazoline auxiliary gives an erythro threo (2R,3S:2S,3S) ratio of 90 10 with 78% e.e. for the erythro-i~omer.'~ \ \ OMe OMe (77) Reagents i BuLi or LDA -85 "C; ii H+/H20; iii CH2Nz Even more impressive is the similar [2,3]sigmatropic rearrangement of the car- banion derived from (78) which after protodesilylation gave (79) in high (>99%) diastereoisomeric purity and with an enantiomeric excess of 98% as judged by the conversion into the naturally occurring pheromone (80). The nearly 100% efficiency of chirality transfer in this example has been explained using the transition-state geometry (81).~~ " S. R. Wilson and M.F. Price J. Org. Chem.1984. 49 722. 72 M. D. Rozeboom J. P. Kiplinger and J. E. Bartmess J. Am. Chem. SOC.,1984 106 1025. 73 Y.Osamura S. Kato K. Morokuma D. Feller G. R. Davidson and W. T. Borden J. Am. Chem. soc. 1984 106 3362. 74 F. Delbecq and N. T. Anh Noun J. Chem. 1983,7 505; M. J. S. Dewar and E. F. Healy J. Am. Chem. SOC.,1984 106 7127. 75 K. Mikami. K. Fujimoto T. Kasuga and T. Nakai Tetrahedron Lett. 1984 25 6011. 76 N. Sayo K. Azuma K. Mikami and T. Nakai Tetrahedron Lett. 1984,25 565; K. Mikami K. Azuma and T. Nakai Tetrahedron 1984. 40,2303. Reaction Mechanisms -Part (i) Pericyclic Reactions \\\ 1 \ \ SiMe SiMe (78) (79) (81) Reagents i Bu"Li -85 "C; ii CsF-MeOH; iii H,-Raney Ni The tendency for groups to undergo [1,5] sigmatropy in substituted cyclopen- tadienes and cyclohexadienes is in the order CHO > MeCO > H > C02Me > CN -C=C > alkyl.The sluggish rate of rearrangement of CN seems anomalous particularly by comparison with its ready migration in substituted cycloheptatrienes where the corresponding order is CHO > CN CGC > MeCO > C02Me > alkyl. The promotion of the triply bonded groups in this latter order is attributable to reduced strain in the bridged rearrangement transition-state (82) compared to (83) (cJ methylenecyclopropane versus methylenecyclopentane) .77 N The ease of [1,5]sigmatropic rearrangement of the alkoxide (84) (in HMPA) is another example of the acceleration of a pericyclic reaction that can be brought about by placement of an alkoxide substituent at the terminus of a breaking a-bond.K'O-Me HMPA HOAc ____ -,,GPh 0-Kt Ph Ph 20 "C Ph Ph Ph Ph + (84) 0 Since the uncatalysed rearrangement of pentaphenylcyclopentadienol requires heating at 173 "C and the migratory aptitude of methyl is much less than that of phenyl the acceleration here is considerable. These rearrangements have been shown to be stereospecific with retention of configuration in the migrating group.78 77 P. J. Battye and D. W. Jones J. Chem. Soc. Chem. Commun. 1984 1458. 78 . P. J. Battye and D. W. Jones J. Chem. Soc. Chem. Commun. 1984 990. R. S. Atkinson At 126 "C the ratio kendo/k,, for [1,5]sigmatropic rearrangement of hydrogen in (85) has been determined as 6.8 by indirect means and has been interpreted in terms of an interaction of gnorbo,.nyl and n-molecular orbitals inducing a twisting of the C-4 Ir-orbital and facilitating migration of the endo-H.79 Carpenter's model for [1,5]sigmatropic rearrangement in a cyclopentadiene is a bicyclo[3.1 .O]hexatriene (86) polarized as shown with the negative dipole distributed over C-2 (C-3) and C-4.A study of solvent effects kinetics thermodynamic parameters and regiospecificity for [1,5]sigmatropic rearrangement of a number of substituted spiro[4,4]nona-l,3-dienessupports this model with (87) rearranging most rapidly and regiospecifically to (88) and (89) rearranging least rapidly to (90).*' 2 4 / (86) (87) R' = CN,R2 = H (88) (89) R' = H R2 = OMe 79 W. N. Washburne and R.A. Hillson 1. Am. Chem. Soc. 1984 106,4575. 80 K. S. Replogle and B. K. Carpenter J. Am. Chem. SOC.,1984 106 5751.