12 Aliphatic Compounds Part (i) Hydrocarbons By R. S. ATKINSON Department of Chemistry The University Leicester LEI 7RH 1 Acetylenes Recent reviews of acetylene chemistry include coverage of addition reactions of tertiary phosphorus compounds with electrophilic olefins and acetylenes,' the chemistry of a-acetylenic ketones,2 1,3-dipolar cycloadditions to alkyne~,~ thermal rearrangement of acetylenes and cyclization of a,@-linear diacetylenes; and catalytic semihydrogenation of the triple bond.5 A book on naturally occur- ring acetylenes has also appeared.6 A promising alternative to the Lindlar catalyst for reduction of acetylenes to cis-olefins uses a particular nickel (P-2) catalyst prepared simply by reduction of nickel@) acetate with sodium borohydride in ethanol.The high cis:trans ratios (30 :1)ofolefins obtained areincreasedfurther by thepresence~fethylenediamine.~ The enormous synthetic potential of organoboron chemistry continues to unfold.8 Trialkylboranes react with alkali-metal acetylides to give alkali-metal 1-alkynyltrialkylborates. Addition of iodine induces the transfer of one of the R groups on boron to the adjacent carbon and high yields of acetylene (1) are ~btained.~ Providing the starting organoborane is readily available secondary alkyl and aryl groups may be transferred giving acetylenes which cannot be prepared by nucleophilic displacement using alkali-metal acetylides. ' M. A. Shaw and R. S. Ward Topics Phosphorus Chem. 1972,7 1. R. L. Bol'shedvorskaya and L. I. Vereshchagin Uspekhi Khim.1973 42 51 1. J. Bastide J. Hamelin F. Texier and Y. Vo. Quang Bull. SOC. chim. France 1973,2555. W. D. Huntsman Intra-Sci. Chem. Reports 1972,6 151. E. N. Marvel1 and T. Li Synthesis 1973 457. 'Naturally Occurring Acetylenes' F. Bohlmann T. Burkhardt and C. Zdero Academic Press London 1973. C. A. Brown and V. K. Ahuja J.C.S. Chem. Comm. 1973 553. * P. I. Paetzold and H. Grundke Synthesis 1973 635. A. Suzuki N. Miyaura S. Abiko M. Itoh H. C. Brown J. A. Sinclair and M. M. Midland J. Amer. Chem. SOC.,1973,95 3080. 348 Aliphatic Compounds-Part (i) Hydro carbons 349 Terminal alkynes are converted into ketones by alkylation or protonation of lithium alkynyltrialkylborates followed by oxidation. Alcohol toluene-p-sul- phonates can be used for the alkylation step protonation with methanesul- phonic acid gave products with R2 = H after oxidation (Scheme l)." R' I R:B + LiCrCRZ d'g'yme Li[R:BCrCRZ] 7RiBC=CR2R3 1)' R1COCHR2R3 Reagents i R3X;ii H,O,.Scheme 1 Conjugated enynes e.g. (2) are formed from alkenylboranes (3) by treatment with lithium acetylides followed by iodine-sodium hydroxide. The reaction HC=C(CH,),CH,OSiMe (ti) , ZBH LiC-CPr I Pr Pr & C C \ 'I C I,-THF (tii,B< /H H /c=c\ (CH,),CH,OSiMe 'NaOH H /c=c\ (CH,),CH,OSiMe A. Pelter C. R. Harrison and D. Kirkpatrick J.C.S. Chem. Comm. 1973 544. 350 R.S. Atkinson gives the trans-enyne which can be converted into a cis-trans-diene by cis- hydrogenation of the triple bond using known methods and illustrated by synthe- sis of the insect pheromone bombykol(4).l1 For trans-trans-dienes an alternative method has been devised which involves stepwise addition of two acetylene units (Scheme 2). Oxidative work-up provides erg-unsaturated ketones.' ' R2 R2 H R2 H R' \ /H /c=c\ / /c=c\H H H%\//C=C\ R' / /c=c\H \ /H /c=c\ //CCH2R' H 0 +"\OMe Reagents i CIC-CR'; ii HC=CR2; iii NaOMe; iv H202; v H +. Scheme 2 A stereospecific route to vinyl halides from acetylenes uses catechol esters of trans-alkenylboronic acids (5) prepared by hydroboration of alkynes with catecholborane. Treatment with two molar equivalents of bromine in methylene chloride followed by base gives cis-alkenyl bromides (6).This inversion of configuration on bromination is in contrast to the trans-alkenyl iodide (7)obtained by addition of sodium hydroxide-iodine to trans-alkenylboronic acids (8). Substituted pyridines can be prepared in reasonable yield by the reaction of two moles of acetylene with one mole of nitrile in the presence of a catalytic amount of a n-cyclopentadienylcobaltcomplex. The mechanism is thought to involve a cobaltacyclopentadiene intermediate (Scheme 3). Acetylene itself is of limited value in the Diels-Alder reaction owing to its sluggish reaction and the difficulty associated with its handling. Vinylene thiono- carbonate(9)and 2-phenyl-A4-1,3-dioxolen (10)have been suggested16 as acetylene ' E. Negishi G. Lew and T. Yoshida J.C.S. Chem.Comm. 1973 874. E. Negishi and T. Yoshida J.C.S. Chem. Comm. 1973 606. l3 H. C. Brown T. Hamaoka and N. Ravindran J. Amer. Chem. Soc. 1973,95,6456. l4 H. C. Brown T. Hamaoka and N. Ravindran J. Amer. Chem. SOC.,1973,95 5786. Y. Wakatsuki and H. Yamazaki Tetrahedron Letters 1973 3383. l6 W. K. Anderson and R. H. Dewey J. Amer. Chem. SOC.,1973,95 7161. Aliphatic Compounds-Part (i) Hydrocarbons 351 R H R Br \/ i Br,-CH,CI, \ / RC=CH -+ ii N~OM~-M~OH’ /c=c\ H /c=c\B,o H H (n-C5H5) PPh, \/ HC-CH + (n-C,H,)Co(Ph3P) -+ A HH il (n-C,H,) PPhj \/ (n-C,H,)Co( PPh3) + R = Me Ph PhCH, or MeO,CCH Reagents i C,H,; ii RCN. Scheme 3 synthons for use according to Scheme 4. (9) and (10) were obtained by reverse Diels-Alder fragmentation of their furan adducts.The butyl-lithium-induced cycloreversion of dioxolans to olefins (Scheme 4) is not generally applicable” but a new method for conversion of thionocarbonates into alkenes uses bis(cyc1o- octa-l,5-diene)nickel. Thionocarbonates of erythro- and threo-4-methylpentane- 2,3-diol (11) and (12) are converted stereospecifically into cis-and trans-4- methylpent-2-ene respectively on stirring in dimethylformamide. A nickel-containing intermediate is inyolved. ’* Synthesis of the marasmic acid skeleton (13) has been accomplished by addition of dimethyl acetylenedicarboxylate (DMAD) to the diene (14) followed by stereo- specific cyclopropanation. l9 l7 J. N. Hines M. J. Peagram E. J. Thomas and G. H. Whitham J.C.S. Perkin I 1973 2332.M. F. Semmelhack and R. D. Stauffer Tetrahedron Letters 1973 2667. l9 S. R. Wilson and R. B. Turner J. Org. Chem. 1973,38 2870. R. S. Atkinson 0 0 Reagents i [)=S; ii (RO),P; iii. C0>Ph; iv BuLi; v HCrCH. 0 H Ni(cod),. DMF. 7H 65 “C. 45 h ,c=s ___,Me H Me Me *Me Me Ni(cod) . Me DMF 65 “C.45 h ____) Me H Me C0,Me Me02C&e Me 95 % Me0,C / Me (14) (13) The highly strained cyclo-octa-1,5-diyne (15) has been isolated. It is stable in crystalline form at 0 “Cwith exclusion of air and X-ray analysis shows that the molecule deviates only slightly from planarity.” 2o E. Kloster-Jensen and J. Win Angew. Chem. Internat. Edn. 1973 12 671. A lip hat ic Compounds-Part (i) Hydrocarbons A potentially useful acetylene is (16),prepared from methyi vinyl ketone by the route shown in Scheme 5.21 H,C=CH H2C=CH Me \c=o , I 11 Me / U 0 II p" J HCGCC Me HCGCCH Me Reagents i (CH,OH),-H +;ii distil; iii 0,; iv HC=CMgBr; v CrO,.Scheme 5 Among mechanistic investigations involving acetylenes is an analysis of the silver(1)-catalysed propargyl-allenyl ester rearrangement of (17) to (I 8).22 By means of 8Oand 14Clabelling and using optically active and diastereoisomeric Ar yo y3 slow. R2 Scheme 6 '' E. F. Hahn J. Org. Chem. 1973,38 2092. 22 H. Schlossarczyk W. Sieber M. Hesse H.-J. Hansen and H. Schmid Helu. Chim. Acta 1973 56 875. 354 R.S. Atkinson esters a [3s,3s]-sigmatropic rearrangenient is shown to be involved (Scheme 6).The role played by the silver(1) ion is n-complex formation with the triple bond in (17) and the double bond which is not involved in the transition state in (18). Thus this rearrangement is of a type which has been recently described as a charge-induced sigmatropic rearrangement and is different from other transforma- tions of strained molecules induced by silver ions. Thermal Claisen rearrangement of 2,6-dichlorophenyl propargyl ether (19) gives the benzofuran (20) and the benzopyran (21) as the major products. These and other minor products are derived from a radical C-Cl homolysis after the initial [3s,3s]-sigmatropic rearrangement (Scheme 7).2 (21) Scheme 7 By choosing conditions benzopyrans or benzofurans can be obtained by pyrolysis of aryl propargyl ethers containing a free cc-po~ition.~ 2,6-Dimethyl-substituted-phenyl propargyl ethers (213)give tricyc10[3,2,1,0~~~]- oct-3-en-8-one derivatives (23) on heating.24 The corresponding methylene derivatives have been prepared and their thermolysis has been studied.25 In the case of the dideuteriated compound (24),acetylenes (25)and (26) are obtained 23 N.Sarcevic J. Zsindely and H. Schmid Helo. Chim. Ada 1973,56 1457. 24 J. Zsindely and H. Schmid Helo. Chim. Am 1968 51 1510. ” P. Gilgen J. Zsindely and H. Schmid Helo. Chim. Acta 1973 56 681. Aliphatic Compounds-Part (i) Hydrocarbons by two competitive reverse Diels-Alder reactions followed by aromatization via [3s,3s]-sigmatropic rearrangements (Scheme 8).The latter are considered to be concerted although many other semibenzene-benzene rearrangements proceed uia radical pathways. RZ A o* DYD Reagents i Ph,P=CH Scheme 8 Treatment of aliphatic nitroso-amides with base yields unstable diazotates. These react intramolecularly with triple bonds with a substituent effect that suggests a nucleophilic attack.26 The mechanism proposed and supported by deuterium labelling (Scheme 9) is strongly reminiscent of the Favorskii with the cyclopropanone opening depending upon the carbanion-stabilizing ability of the substituent R. Using optically active pent-1-yne-3-diazotate (27 ;R =Et) the ester (28) was isolated with 88 inversion of configuration which eliminates the planar oxyallyl cation (29)as the precursor of the cyclopropanone.The latter may z6 W. Kirmse A. Engelmann and J. Hesse J. Amer. Chem. SOC.,1973 95 625; Chem. Ber. 1973 106 3073; W. Kirmse and A. Engelmann ibid. p. 3086. R. S. Atkinson LR-AH -0 OR OR (29) (31) \ MeCHRC0,Me + RCH,CH,CO,Me (28) Reagents i NaOMe-MeOH; ii MeOH. Scheme 9 arise by backside displacement of nitrogen either within the methyleneoxadiazo- line anion (30) giving the cyclopropanone enolate (31) or by using the n-electrons in the methyleneoxadiazoline (32). Metallation of isobutene with butyl-lithium in the presence of tetramethylethyl- enediamine gave the methylallyl anion (33)and the trimethylenemethane dianion (34). In spite of the introduction of a second negative charge this lithiation step occurs faster than the first.This has been ascribed to aromatic character of six electrons in four parallel p-~rbitals.~’ Dimetallation ofinternal acetylenes occurs by abstraction of both protons from the same carbon. 1.r. data in several solvents support the view that these dianions exist in either the sesquiacetylenic (35) or allenic form (36) according to the conditions. Thus a change to more co-ordinating solvents (e.g.HMPT) produces a shift in the position of the absorption band from -1800 to 2050 cm-1.28 Li / 4 \ Li R’ 27 J. Klein and A. Medlik J.C.S. Chem. Comm. 1973 275. 2a J. Klein and J. Y. Becker J.C.S. Chem. Comm. 1973 576. Aliphatic Compounh-Part (i) Hydrocarbons 2 Alkarres Cyclo-octane exists predominantly in the boat-chair conformations although the crown family (Figure 1) may become more important with the introduction of substituents or heteroatoms into the ring.A detailed study of cyclo-octane using boat-chair family 11 crown family Figure 1 13Cn.m.r. and of cis-1,2-hz-[2H,,]cyclo-octane using 'H n.m.r. at low tempera- tures has shown that cyclo-octane itself exists to a small extent (6% at room temperature) in the crown-family conformati~n.~~ Intermolecular hydrogen exchange and alkylation of alkanes with their parent carbenium ion salts have been studied under stable ion conditions in superacid media. The reactions involve electrophilic attack by the carbenium ion on the C-H or C-C bonds oiu triangular three-centre-bonded carbonium ion transition states.30 3 Allenes Recent progress in the chemistry of a1lenes3l and the synthesis absolute con- figuration and optical purity of chiral allene~~~ has been reviewed.Allene reacts with various amines or carbon acids in the presence of catalytic amountsof palladium(0) or rhodium(1) complexes to give high yields of butadienes. Mono(dieny1)- or bis(dieny1)-derivatives could be obtained by varying the reaction temperature or mole ratio of reactants (Scheme 10). The products formed the corresponding mono- and bis-Diels-Alder ad duct^.^^ 29 F. A. L. Anet and V.J. Basus J. Amer. Chem. SOC.,1973,9S 4424. 3o G. A. Olah Y.K. Mo and J. A. Olah J. Amer. Chem. SOC.,1973,9S 4939; G. A. Olah J. R. DeMember and J.Shen ibid. p. 4952; G. A. Olah Y. Halpern J. Shen and Y. K. Mo ibid. p. 4960. 31 T. Okamoto Bull. Inst. Chem. Res. Kyoto Univ. 1972 SO 450. 32 R. Rossi and P. Diversi Synthesis 1973 25. 33 D. R.Coulson J. Org. Chem. 1973 38 1483. 358 S.A t k inson CH =C=CH R2 R3 = CN CO,Et COMe Reagents i R'R'NH; ii CH,=C=CH,; iii CH,R3R4. Scheme 10 The salt (37)can beobtained from the readily available 1,3-diamino-1,3-dichloro-ally1 cation (38)by treatment with dimethylamine. This salt and the diethoxy- analogue (39) prepared by alkylation of NN-dimethyl-P-ethoxy-P-dimethyl-amino-acrylamide with triethyloxonium tetrafluoroborate are the protonated forms of allenetetramine (40) and dialkoxydiamino-allene respectively. The corresponding allenes are obtained as distillable liquids on treatment with butyl lithium or sodium amide in liquid ammonia but react readily with electrophiles to give substituted 1,1,3,3-tetrakis(dialkylamino)allylcations e.g.(41) and (42).34 Gt Me,N NMe EtO BF4- Me,N NMe NMe2 Me2N NMe H H H (37) (39) NMe, Me,N \ /NMe i. PhOCN c10,-Me,N /c=c=c TEiz NMe, \ Me,N NMe CN NMe2 Me,N NMe H. G. Viehe Z. Janousek R. Gompper and D. Lach Angew. Chern. Znrernat. Edn. 1973 12 566. Aliphatic Compounds-Part (i) Hydrocarbons A series of racemic allenes were partially hydroborated with the chiral (+)-tetra-3-pinanyldiborane (43). In every case examined the recovered allene was enriched in the (R)-enantiomer. The model used to explain this result also correctly predicts the configuration of chiral alcohols produced from simple olefins.For the case of alkyl substituted allenes both vinylborane (44) and allylborane (45) RHC CHR I1 C !HR major/CHzR '--:,minor RHcyH (44)/HB (43) CH,B' \ (45) are produced the optical purity of the recovered allene would have been higher but for the minor allylborane formation which is predicted by the model to remove the (R)-enantiomer preferentially. The mechanism of allene dimerization continues to attract attention. If the allene dimerization within (46) takes place uia a biradical route then it would give rise to (47),a species which can also be generated by pyrolysis of (48) (49) or (50). An analysis of the gas-phase thermolysis products of (46) (48) (49) and (50) at -110-120°C shows that (47)is a common intermediate but is generated from (46) with excess vibrational energy.36 A slightly different interpretation of the results of thermolysis of (46) (48) and (50) is given in terms of two conformations (51) and (52) of the reactive 2,3-dimethylene-l,4-cyclohexadiylbiradical (47) a'CH k.; CH (51) 35 W.R.Moore H. W. Anderson and S. D. Clark J. Amer. Chem. SOC.,1973,95,835. 36 W. R.Roth M. Heiber and G. Erker Angew. Chem. Inrernar. Edn. 1973,12,504; W. R. Roth and G. Erker ibid. p. 503; W. R. Roth and G. Erker ibid. p. 505. 360 R. S. Atkinson which react before achieving conformational equilibrium. 37 Thermolysis of (46) in solution gives mainly dimerization products of (47) and CIDNP signals from the dimers are observable.The contrasting behaviour of(47) in the gas phase and in solution may be the result of two different spin states.36 Addition of electron-rich olefins to electron-deficient allenes has been studied with the prospect that these allenes might resemble keten in their reactivity. From the reaction of the enamine (53) (2 equivalents) and the allene precursor (54) the cyclobutane (55) is isolated in which the two methyl singlets at C-4 coalesce to a singlet in the n.m.r. spectrum at 76 "C in CDC1,. An equilibrium between (55) and the zwitterion (56) with rapid rotation around the C-3-C-4 bond explains this phenomenon. Prolonged heating of (55) results in complete conversion into (57) which requires C-1 -C-4 bond rotation.38 Me /NMe NMe CN \ /c=c\ + Me,CHC=C(CN) + I Me H c1 Me Me Me Me + Me ,CN 11 lr1r Me,N Me (57) Me Treatment of 2,3-dipropargylnaphthalenewith potassium t-butoxide in t-butyl alcohol under carefully controlled conditions allows the isolation of the crystalline diallene (58).A solution of(58) in oxygen-saturated methanol yields the crystalline peroxide (59). The o-quinodimethane (60) is presumed to be an inter- mediate and can be trapped by dimethyl fumarate or maleate. No analogous peroxide was isolable starting from (61).,' \I (61) (59) (60) 37 W. Grimme and H.-J. Rother Angew. Chem. Internat. Edn. 1973 12 505. 38 R. Gompper and D. Lach Angew. Chem. Internat. Edn. 1973,12 567. 39 C. M. Bowes D. F. Montecalvo and F.Sondheimer Tetrahedron Letters 1973 3181. Aliphatic Compounds-Part (i) Hydrocarbons 361 4 Olefins Recent reviews involving olefins include the stereochemistry of biogenetic-like olefin cyclizations ;40 aromatic substitution of olefins by palladium salts ;41 homogeneously catalysed dimerization of olefins ;42 addition reactions of butadi- ene catalysed by palladium complexes ;43 structure of 1,3-diene hydrocarbons and their reaction with electrophilic reagents;44 conjugate addition reactions of organocopper reagents ;45 protection of carbon-carbon multiple bonds ;46 syntheses of seven- and five-membered rings from ally1 cations ;47 and the stereo- chemistry of double bonds by n.m.r. spectro~copy.~~ A volume covering open- chain and cyclic polyenes and enynes has a~peared.~’ A stereospecific synthesis of trisubstituted olefins involves the addition of organocopper reagents to acetylenes in the presence of alkyl iodides.This method has been extended to the synthesis of allylic alcohols as illustrated for the case of (62)” Me EtCuMgBr I. MeC=CH. \ c=c/H ~ iiCH,OCH,CH,CI / \ 1 Et CH20 Br I CH,CH,Cl Me \ /H c=c Et /\ CH20H 70 % (62) overall Quaternary ammonium salts containing large alkyl residues function as phase-transfer catalysts by ion-pair formation in the aqueous phase with anionic reactants and their subsequent delivery to the waiting substrate in the organic phase. Using the dichloromethane-water two-phase system and tetrabutyl- ammonium iodide (TBAI) Wittig olefination of aromatic aldehydes with non- stabilized ylides is feasible.In aqueous solution only degradation of the phos- phonium salt to phosphine oxide occurs. Omission of the TBAI is possible since the phosphonium salts themselves can function as phase-transfer catalysts5 40 K. E. Harding Bioorg. Chem. 1973 2 248. 41 I. Moritani and Y. Fujiwara Synthesis 1973 524. ” J. Hetflejs and J. Langova Chem. listy 1973 67 590. 43 J. Tsuji Accounts Chem. Res. 1973 6 8. 44 V. S.Aksenov Sovrem. Probl. Org. Khim. 1971 33. 45 G. H. Posner Org. Reactions 1972 19 1. 46 D. W. Young in ‘Protective Groups in Organic Chemistry’ ed. J. F. W. McOmie Plenum Press London 1973. 47 H. M. R. Hoffmann Angew. Chem. Internat. Edn. 1973,12 819. 48 G.J. Martin and M. L. Martin Progr. N.M.R. Specrroscopy 1972 8 163. 49 ‘Methods of Organic Chemistry’ (Houben-Weyl) Vol. 5 Part Id ‘Open-chain and cyclic polyenes enynes’ 4th edn. E. Mueller Thieme Stuttgart. J. F. Normant G. Cahiez C. Chuit and J. Villieras Tetrahedron Letters 1973 2407. 5‘ G. Mark1 and A. Merz Synthesis 1973 295. R.S. Atkinson 2,3-Bis(bromomethyl)buta-1,3-diene (63) has been prepared by zinc-copper couple debromination of the tetrabromide (64) in ether-hexamethylphosphor-triamide and found to be stable in solution. Both (63)and its Diels-Alder or other addition products are potentially valuable in synthesis. The heterocycles (65) (66),and (67)are readily obtainable and the reactive allylic bromines in (63)may be displaced by a variety of nucleophiles.Additionally a 1,3-diene may be regenerated after Diels-Alder addition i.e. (63)-+ (68).52 H2cc:: H2czx (65)(66) X = S0 Br H2C H2C (67) X = NR /MeO,CCrCCO,Me C02Me Br C0,Me H2C x H,C’ x X (71) X = CN (69) X = CN (72) X = C02Me (70) X = C0,Me Improved routes have been reported to the potentially useful 2,3-dicyano-and 2,3-dimethoxycarbonyl-butadienes(69) and (70) by thermal ring opening of the corresponding cyclobutenes (71) and (72). Diels-Alder cycloadditions of (69) occur readily with electron-rich olefins with an inverse of the normal electron demand. Iron pentacarbonyl has been found to reduce enol acetates vinyl chlorides and ap-unsaturated aldehydes to the corresponding olefins.The procedure simply involves heating the substrate and iron pentacarbonyl under reflux in dibutyl ether. A radical mechanism is impli~ated.~~ A method of generating allyl-and methallyl-lithium which avoids troublesome coupling reactions uses butyl-lithium-tetramethylethylenediaminetreatment of propene or i~obutene.~2-Methoxypropene and other useful vinyl ethers are 52 Y. Gaoni Tetrahedron Letters 1973 2361 ; S. Sad& and Y. Gaoni ibid. p. 2365. D. Bellus and C. D. Weis Tetrahedron Letters 1973 999. s4 S. J. Nelson G. Detre and M. Tanabe Tetrahedron Letters 1973 447. 55 S. Akiyama and J. Hooz Tetrahedron Letters 1973,4115. Aliphatic Compounds-Part (i) Hydrocarbons conveniently prepared by succinic anhydride-benzoic acid-mediated removal of methanol from the corresponding dimethylacetal~.~~ N-p-Tolylvinylmethylketenimine(73) has been prepared from the amide (74) and in contrast to vinylketens was fairly stable at room temperature and even distillable.(73) exhibits ambident character in cycloadditions ;thus with electron- deficient dienophiles e.g. dicyanostyrene the adduct (75) is formed regiospecific- ally and can be hydrolysed by mild acid to the ketone (76). An electron-rich H,C=CH CH,=CH \ i Ph,PBr,; \ CHCONHAr ii,E1,N C=C=NAr / / Me. Me (74) (73) diqophile however prefers to react across the [C=C(aromatic) and C=N]- diene system. N-Diethylaminophenylacetyleneand (73) in acetonitrile gave a quantitative yield of the quinoline (77).57 CHMe (77) Addition of the acid chloride of monoethyl fumarate to the piperidine (78) yielded a crystalline adduct (79) in 70 % yield in which four contiguous centres are created at one blow in an intramolecular Diels-Alder addition.Their configurations are assigned by n.m.r. with the assumption of endo-addition and using the fact that base epimerizes two of these centres. Pentacyclic aza- or diaza-steroid skeletons can conveniently be constructed from (80).58 Intramolecular ene reactions have been used for the synthesis of substituted pyrrolidines exemplified by the conversion of (81) into (82). In general the 56 M. S. Newman and M. C. Vander Zwan J. Org. Chem. 1973,38,2910. '' E. Sonveaux and L. Ghosez J. Amer. Chem. SOC.,1973,955417. 58 H. W. Gschwend Hefv.Chirn. Acfu 1973,56 1763; H. W. Gschwend A. 0.Lee and H. P. Meier J. Org. Chem. 1973 38 2169. R.S. Atkinson _7 (78) (79) Ph” C0,Me reaction is highly stereoselective and it has been used in a key step for synthesis of the naturally occurring p-acorenol (83) (Scheme 1 l).59 m& C0,Et 280 “C _____ + 3 days. 19% several steps OH (83) Scheme 11 ’’ W. Oppolzer E. Pfenninger and K. Keller Helv. Chirn. Acta 1973 56 1807 W. Oppolzer ibid. p. 1812. Aliphatic Compounds-Part (i) Hydrocarbons Members of the PGC series of prostaglandins are of considerable interest; they are intermediates on the deactivation pathway of A prostaglandins (PGA’s) to B prostaglandins (PGB’s) (Scheme 12) in mammalian systems.0 PGA PGC PGB Scheme 12 The reaction of the lactol (84) with two equivalents of tri-irondodecacarbonyl gives the stable conjugated diene complex (85). Oxidation ofthe derived hydroxy- carboxylic acid (86) with Collins’ reagent gave the tetrahydropyranyl (THP) derivative of PGC (87) in which the iron is removed under conditions mild enough to avoid isomerization of the sensitive cyclopentene double bond.60 OH CO,H pyridine = O eCozH ‘OTHP The nickel hydrogenation catalyst for acetylenes referred to earlier is also highly sensitive to the environment of the double bond permitting selective reduction of less hindered olefins in the presence of more hindered ones. Thus oct-1-ene can be 6o E. J. Corey and G. Moinet J. Amer. Chem. SOC.,1973,95 7185.366 R. S. Atkinson reduced in the presence of cyclohexene. Hydrogenolysis of benzylic and allylic alcohols and ethers did not occur with this catalyst.6' An increasing number of cycloeliminations corresponding to reverse anionic 1,3-cycloadditions are being uncovered. The lithiated triazolidine (88) is obtained (73%) from trans-trans-1,3-diphenyl-2-aza-allyl-lithium (89) and azobenzene at temperatures below 20 "C. Above 60 "C cycloreversion back to the starting components occurs and the 2-aza-ally1 anion is trapped by trans-stilbene to give the pyrrolidine (90).62 Ph Ph PhN=NPh H Ph ' ' 20°C i. trons-stilbene +A Ph-H H.J-XH => H-AN,!j H 60°C Ph Li Ph Ph H Ph Some rationalization of the regioselectivity (ortho :meta) and reactivity obtaining in the Diels-Alder addition of monosubstituted olefins and dienes is possible using experimentally available frontier-orbital energies and calculated orbital coefficient^.^^ Acid catalysis has a profound effect on the Diels-Alder reaction and large rate accelerations increased regioselectivity and stereo- selectivity occur.The predominant frontier-orbital interaction in the reaction with 'normal electron demand' is the diene HO and dienophile LU*. Rate accelera- tions are the result of lowering of the energy of the dienophile LU in the protonated form. Stereoselectivity (endo :exo ratio) is controlled by secondary orbital interactions between the diene HO and the dienophile LU which are augmented in the protonated case as a result of the larger coefficient at the carbonyl carbon (Figure 2).64 acrolein protonated acrolein case case Figure 2 6' C.A. Brown and V. K. Ahuja J. Org. Chem. 1973,38,2226. 62 T. Kauffmann A. Busch K. Habersaat and B. Scheerer Tetrahedron Letters 1973 4047. 63 K. N. Houk J. Amer. Chem. SOC.,1973,% 4092. 64 K. N. Houk and R. W. Strozier J. Amer. Chem. SOC.,1973,95,4094. * HO highest occupied LU lowest unoccupied. Aliphatic Compounds-Part (i) Hydrocarbons A similar frontier-orbital treatment has also been applied to regioselectivity in concerted cycloadditions of 1,3-dipoles to olefins and the conclusion experi- mentally verifiable is that unidirectional addition of monosubstituted dipolaro- philes should no longer be observed when the latter are highly ele~tron-deficient.~~ Primary carbon-14 kinetic isotope effects in the 1,3-dipolar addition of N-a-diphenylnitrone and styrene are interpreted as being consistent with a concerted rather than a biradical mechanism.66 The stereochemistry of hydrogen and formyl-group addition to alkenes (the ‘0x0’ process) has been determined using (E)-and (2)-3-methyl-pent-2-ene and a hydridocarbonyltris(tripheny1phosphine)rhodium catalyst.Analysis of the dia- stereoisomeric composition of the major product (91) from each isomer shows overwhelming cis-addition of CHO and H allowing for the small amount of isomerization of the initial olefins by the catalyst which is shown to occur by deuteri~formylation.~’ Me Me Me I Co H, [(Ph,P),RhH(CO)] CH,CH,CHCHCHO I1 CH,CH,C=CHCH Methoxymercuration of ethylene proceeds stereospecifically by trans-addition as is shown using cis- and trans-dideuterioethylene.threo- and erythro-1,2-dideuterio-2-methoxyethylmercuricchloride assignments were made on the basis of solvent effects upon the vicinal proton-proton coupling constants.68 A number of penta- and hexa-substituted butadienes have been prepared by substitution of one or both hydrogens in (E,E)-1,2,3,4-tetrachlorobuta-1,3-diene (92). In (93) the benzylic hydrogens which show an AB system at 34°C are diastereotopic as a result of the non-planarity of the butadiene. Coalescence at a higher temperature (58 “C)is the result of accelerated twisting about the central C-C bond which interconverts the magnetic environments of HAand H,.Although the substituents which are introduced are ‘outside’ in the intermediate planar transoid conformation yet they exert significant effects upon the twisting barrier. 65 J. Sims and K. N. Houk J. Amer. Chem. SOC.,1973,95 5798. 66 B. M. Benjamin and C. J. Collins J. Amer. Chem. Sou. 1973,95,6145. 67 A. Stefani G. Consiglio C. Botteghi and P. Pino J. Amer. Chem. SOC.,1973,95,6504. 68 T. Ibusuki and Y. Saito J. Organometallic Chem. 1973 56 103. 69 G. Kobrich B. Kolb A. Mannschreck and R. A. Misra Chem. Ber. 1973,106 1601.