8 Aliphatic Compounds Part (i)Hydrocarbons By K.J. TOYNE Department of Chemistry The University of Hull Hull HU6 7RX 1 Alkanes The reactions of alkyl halides with metal hydrides and complex metal hydrides have been examined in order to distinguish those reagents which are effective for hydrodehalogenation from those which can be utilized for reduction of functional groups without significant attack on the halogen substituent.' Lithium triethyl- borohydride and lithium aluminium hydride were found to be useful for hydro- dehalogenation reactions whereas borane and dialkylboranes were essentially inert toward alkyl halides. The reactions of lithium hydride with several functional groups in the presence of transition-metal halides have shown that terminal alkenes can be reduced to alkanes with LiH + VC13 whereas internal alkenes and alkynes are completely unreactive.* This reagent could therefore be used for selective reduction of a terminal double- bond in the presence of a triple-bond (in enynes) or an internal double-bond (in dienes).Complex aluminohydrides in the presence of catalysts have also been used for the reduction of alkynes and alkenes. Sodium and lithium aluminium hydrides and some of their derivatives were allowed to react with alkenes and alkynes using titanocene dichloride [(c~)~TiCl~] With terminal alkenes the reactions were as a cataly~t.~ complete in 10 minutes at room temperature (Scheme l),and internal alkynes also led readily to cis-alkenes but the reaction was unsatisfactory with internal alkenes and terminal alkynes.The reactions also provide a route to alkyl- and vinyl- aluminium compounds. Hydroalumination of alkenes has also been achieved with [(c~)~TiCl~] [(c~)~Ti(H)Cll .-+ LiAIH3CI 11 1 RCH=CH2 -+ [RCH2CH2Ti(CI)(Cp)2]+RCH2CH2AIH3Li+ [(c~)~Ti(H)Cll I \ iii I \" c L RCH2CH3 RCHzCHzD Reagents i LiAIH, THF; ii [(Cp),Ti(H)CI] THF; iii H,O; iv D,O Scheme 1 ' S. Krishnamurthy and H. C. Brown,J. Org Chem. 1980.45 849. ' E. C. Ashby and S. A. Noding J. Org. Chem. 1980,45 1041. ' E. C. Ashby and S. A. Noding J. Org Chem. 1980,45 1035. 107 108 K. J. Toyne tri-isobutylalane and [(Cp),ZrC12] (as the catalyst) and this reaction is successful in the presence of groups such as OH SPh and Br which may interfere with alternative hydroalumination procedures (Scheme 2).4 In this procedure both terminal and internal alkenes react to give the alkane.I [(Cp)2ZrC12]-[(Cp)2Zr(C1)Bui]+[(Cp)zZr(H)Cl]+ Me2C=CH2 [(Cp)2Zr(H)Cl]A [RZr(Cl)(Cp)z] RAIBu’2 + [(Cp),ZrCl2] 1 iv RH Reagents i Bu’,AI 1,2-dichloroethane; ii alkene; iii Bu’,AICI; iv H20 Scheme 2 Decarboxylation of acids to alkanes by using an ester from which the efficient generation of carboxyl radicals was achieved in an ‘a1kene’-forming radical-frag- mentation reaction has been described (Scheme 3).’ Esters of truns-9-hydroxy-10- phenylthio-9,lO-dihydrophenanthrene(1)or its 10-chloro-analogue (2),which lead to a fully aromatic system on fragmentation have been used and the hydrocarbon is formed in mild neutral conditions from primary secondary and tertiary acids with tri-n-butylstannane.R’ R‘ 1 RH tR-Reagents i Bu”,SnH benzene or toluene azobisisobutyronitrile reflux (i.e. Bu”,Sn -); ii Bu”,SnH Scheme 3 (1) X = SPh (2) x = CI Two methods for deoxygenation of alcohols to alkenes were mentioned in the Annual Report for 197fL6‘ One of these methods for tertiary alcohols and sterically hindered secondary alcohols involved the reduction of the derived carboxylic ester by lithium in ethylamine and now non-hindered secondary and primary alcohols can be reduced in high yield by using their (dialky1amino)thiocarbonylderivatives E. Negishi and T. Yoshida Tetrahedron Left. 1980 21 1501. D. H. R. Barton H. A.Dowlatshahi W. B. Motherwell and D. Villernin J. Chern. Soc. Chem. Cornrnun. 1980.732. K. J. Toyne Annu. Rep. Prog. Chem. Sect. B 1978,75 (a)p. 159 (b)p. 163. Aliphatic Compounds -Part (i) Hydrocarbons S II I ROH __* ROCNEt2 +RH Reagents i K Bu'NH, 18-crown-6 THF Scheme 4 to give the alkane and some of the original alcohol (Scheme 4).' The radical anion which is formed by electron transfer from potassium collapses to form pre- dominantly a stabilized thiocarboxylate anion and a carbon radical; the latter leads to the alkane. It has also been shown that the similar reduction of carboxylic esters in non-nucleophilic media occurs by cleavage of the alkyl-oxygen bond of the derived radical anion to give alkane and carboxylate anion by the major pathway.8 An alternative procedure for the deoxygenation of primary and secondary alcohols is achieved by reduction of chloroformates with tri-n-propylsilane (Scheme 5)9 (see also ref.lOa) and an exceedingly mild desulphurization of thiols using sodium triethylborohydride and ferrous chloride has been used for aromatic benzylic and aliphatic systems." I I1 111 ROH -+ ROCOCI -+ RO-C=O -R. -+ RH + Pr3Si* Reagents i COCI,; ii Pr3SiH (Bu'O),; iii Pr,SiH Scheme 5 The cyano-group in primary secondary or tertiary nitriles is reductively cleaved by highly dispersed potassium on neutral alumina in hexane at room temperature to give the alkane in excellent yield.12 The reagent is prepared by melting potassium over neutral alumina at 150 "C with vigorous stirring in an inert atmosphere.2 Alkenes Synthesis.-Several alternative methods for conventional elimination procedures have been reported. Carefully dried copper(I1) sulphate is a useful catalyst for the dehydration of secondary tertiary benzylic and allylic alcohol^.'^ The procedure simply involves heating the alcohol and the solid catalyst until the alkene distils from the mixture. The predominant Saytzeff and trans-alkene products suggest that formation of a carbonium ion is involved. On the other hand Grignard or organolithium compounds react rapidly with ethylene in the presence of nickel chloride at -20 to 0 "C in ether to give the alkene by abstraction of P-hydride which preferentially gives the less stable Hofmann Terminal (R'CH=CH2) and disubstituted (R'CH=CHR*) alkenes are formed in high yield by the reaction of vicinal dihalides [R'CHXCHY(R* or H)] with sodium methyl- or phenyl-selen01ate.l~ The elimination occurs rapidly at room 'A.G. M. Barrett P. A. Prokopiou and D. H. R. Barton J. Chem. SOC.,Chem. Commun. 1979,1175. A. G.M. Barrett P. A. Prokopiou D. H. R. Barton R.B. Boar and J. F. McGhie J. Chem.SOC.,Chem. Commun. 1979,1173. R. A. Jackson and F. Malek J. Chem. SOC.,Perkin Trans. 1 1980 1207. lo K. J. Toyne Annu. Rep. Prog. Chem. Sect. B 1979 76 (a)p. 127 (b)p. 135 (c) p. 145 (d)p. 139 (e) p. 145. l1 H. Alper and T. L. Prince Angew. Chem. Znt. Ed. Engl. 1980,19 315. l2 D. Savoia E. Tagliavini C. Trombini and A. Umani-Ronchi J. Org. Chem. 1980 45 3227. R. V. Hoffman R.D. Bishop P. M. Fitch and R. Hardenstein J. Org. Chem. 1980,45,917. l4 M. T. Reetz and W. Stephan Liebigs Ann. Chem. 1980 171. M. Sevrin J. N. Denis and A. Krief Tetrahedron Lett. 1980 21,1877. 110 K. J. Toyne temperature except for dichlorides (which need to be heated at SOOC) and the diselenide product can be separated and re-used for preparing the selenolate. syn-Elimination occurs for vicinal dichlorides but in other cases the process involves anti-elimination. The full report has now appeared16 of the method for synthesis of an alkene which uses the triphenylmethyl carbonium ion to abstract hydride ion from an alkyl-iron compound [(C~)Fe(co)~ (CHR'CH2R2)] to give an alkene complex from which the alkene can then be liberated (see also ref.6b).The sequence is useful because 1-and 2-alkyl-iron compounds usually give the terminal alkene and 3-alkyl-iron compounds give only the less stable (Z)-alk-2-ene isomer. The regioselective transformation of a ketone into an alkyl-substituted alkene is now possible by three procedures based on the reactions of enol derivatives. Enol trifluoromethanesulphonatesreact with lithium dialkylcuprates to give the coupling products in high yields (Scheme 6)." Alkyl- aryl- vinyl- and cyclopropyl-cuprates R2 \c=o iii,iv / OR'-CH2 vii H R' CH2 CH2 (4) Reagents i 2,6-di-t-butylpyridine (CF,S02),0 CH,Cl,; ii R3,CuLi THF; iii Li NH, ether; iv (PhO),POCI ether; v R4,Al [Pd(PPh,),] 1,2-dichloroethane; vi Me,SiCI Et,N DMF; vii R5MgX [Ni(acac),] or [NiC12(PPh3)2]or [NiCl,(dppf)] ether; viii 2,4,6-tri-isopropylben- zenesulphonyl hydrazide {'trisyl hydrazide) HCI; ix NNN'N'-tetramethylethylenediamine (TMEDA) hexane BuLi; x R6,B THF; xi I, ether; xii NaOH H,O Scheme 6 have been used and the vinyl reagent gives a route to 1,3-dienes.In the second method enol phosphates (3) react with trialkylaluminiums in a palladium-catalysed reaction to provide a specific transformation of ketones into aIkyl-substituted alkenes (Scheme 6)." Alkenylation and alkynylation are also possible by this method to give dienes and enynes. In the third method a new carbon-carbon bond is formed when the silyloxy-group of silyl enol ethers is substituted by an alkyl or aryl group from a Grignard reagent in a nickel-complex-catalysed reaction (Scheme ,).I9 " D.E. Laycock J. Hartgerink and M. C. Baird J. Org. Chem. 1980 45,291. " J. E.McMurry and W. J. Scott Tetrahedron Lett. 1980 21,4313. K.Takai K. Oshima and H. Nozaki Tetrahedron Lett. 1980 21 2531. l9 T. Hayashi Y. Katsuro and M. Kumada Tetrahedron Lett. 1980 21 3915. Aliphatic Compounds -Part (i) Hydrocarbons 111 The stereo- and regio-chemistry of the reaction depends on the nature of the catalyst; with dichlorobis(triphenylphosphine)nickel(II) [NiC12(PPh3)2] the coup- ling process is regio- and stereo-specific. Phosphine complexes of nickel(@ chloride have also been used to catalyse the coupling of Grignard reagents with alkenyl aryl or allylic selenides.20 The reaction of alkenyl selenides is highly stereospecific and it proceeds with retention of configuration.With alkenyl aryl selenides bond- cleavage occurs on both sides of the selenium atom and two equivalents of the Grignard reagent are required. A further procedure achieves an equivalent transformation of methyl ketones into 1,l-dialkyl-ethenes (Scheme 6).21The trisylhydrazone of the methyl ketone is converted into a trialkyl(viny1)borate (4) and then an alkyl migration from boron to carbon is induced by iodine. Three new procedures permit alkenes to be formed from epoxides in mild stereospecific reactions and one of these methods allows the stereochemistry of a disubstituted ethene to be inverted. The method for inversion can be applied to the alkene directly or to the epoxide and it is based on the formation of a vic-bromo- or vic-chloro-hydrin trifluoroacetate (Scheme 7).22 The halogeno-ester is then HH M R' R' 17"R2+ -MH [X = a1 H H R2 CFJOO CF,COO 0 7 H-A-H R' R2 Reagents i N-bromosuccinimide CF,CO,H or N-chlorosuccinimide CF,CO,H; ii NaI DMF heat; iii LiBr (CF,CO),O or LiCI (CF,CO),O; iv Zn HOAc DMF; v NaI (CF3C0),0 Scheme 7 converted into the iodo-ester by an SN2reaction; the iodo-ester then decomposes to the alkene with inverted geometry.The original alkene can however be regener- ated by reduction of the chloro-ester. A review has appeared which discusses numerous other methods for achieving inversion of alkene~.~~ The second method for generating alkenes from epoxides is based on the reaction of iodohydrins with triphenylphosphine di-iodide to produce an alkene by stereospecific trans-elimina- tion.Since iodohydrins can be formed by the anti-opening of epoxides with hydrogen iodide it is possible to use a mixture of triphenylphosphine hydriodide and triphenylphosphine di-iodide to reduce an epoxide to an alkene of the same stereo~hemistry.~~ The third procedure uses sodium diethyl phosphite and a catalytic amount of tellurium powder to obtain the alkene from an epoxide stereo-~pecifically.~~ Terminal epoxides are deoxygenated most readily and (2)-isomers react more readily than the (,!?)-isomers. Selective deoxygenations can be carried out in some cases especially when a more reactive terminal group is involved. 2o H. Okamura M. Miura K.Kosugi and H. Takei Tetrahedron Lett. 1980 21 87 21 K. Avasthi T. Baba and A. Suzuki Tetrahedron Lett. 1980 21 945. 22 P. E. Sonnet J. Org. Chem. 1980 45 154. 23 P. E. Sonnet Tetrahedron 1980,36,557. 24 P. E. Sonnet Synthesis 1980 828. 25 D. L. J. Clive and S. M. Menchen J. Org. Chem. 1980,45 2347. 112 K.J. Toyne Complex reducing agents such as NaH-RONa-Ni(OAc) are new heterogeneous hydrogenation catalysts which can be used for the partial hydrogenation of alkynes to alkenes at atmospheric pressure and room The selective hy- drogenation of carbon-carbon double-bonds in dienes mixtures of alkenes or unsaturated carbonyl systems is sometimes possible and hydrogenation of aldehydes and ketones can be achieved. The cyano-cobalt complex K3[Co(CN),H] has been known for many years and its further use as a hydrogenation catalyst has now been reported.28 The water-soluble complex is readily prepared from cobalt(@ chloride and potassium cyanide under an atmosphere of hydrogen and it is reactive at room temperature in phase-transfer conditions.It is capable of reducing conju- gated dienes to mono-enes (generally by 1,4-addition) and of converting a@-unsaturated ketones into saturated ketones but isolated carbon-carbon double- bonds and carbonyl groups are not hydrogenated. Regiospecific deoxygenation of allylic alcohols to terminal alkenes can be carried out by the three-step sequence shown in Scheme 8.29The xanthate derivative of the R2 II 0 Reagents i NaH cs,;MeI C6H6 reflux; ii Bu3SnH C6H6 azobisisobutyronitrile at 80 "c;iii HCl or MeC0,H Scheme 8 ally1 alcohol undergoes a [3,3] sigmatropic rearrangement to give a dithiocarbon- ate.The reaction of the dithiocarbonate with tributyltin hydride gives an allylic stannane which is then cleaved to give the terminal alkene. Some other methods for preparing alkenes are given in the section dealing with the reactions of alkynes (p. 120). Reactions of A1kenes.-Alternative methods continue to appear for fundamental alkene reactions such as hydration halogenation hydrohalogenation hydroxyla- tion and epoxidation. Alkenes are converted into alcohols with the hydroxy-group introduced in an anti-Markovnikov fashion by their reaction with TiCI,-NaBH, followed by decomposition of the intermediate with water.30 Vicinal dibromides can be converted into alkenes by reduction at a mercury cathode in DMF; in the case of tetrabromides from dienes the higher alkylated double-bond can be regenerated selectively and so the less alkylated double-bond can be selectively protected as the dibr~mide.~' Complementary to this procedure is the use of pyridinium hydrobromide perbromide in THF or chloroform under mild conditions to achieve the selective dibromination of a non-conjugated diene at the more alkylated (and hence more reactive) d~uble-bond.~ 26 J.Brunet P. Gallois and P. Caubere J. Org. Chem. 1980 45 1937. '' P. Gallois J. Brunet and P. Caubere J. Org. Chem. 1980 45 1946. *' D. L. Reger M. M. Habib and D. J. Fauth J. Org. Chem. 1980,45 3860.29 Y. Ueno H. Sano and M. Okawara Tetrahedron Lett. 1980 21 1767. 30 S. Kano Y. Tanaka and S. Hibino J. Chem. SOC.,Chem. Commun. 1980,414. 31 U. Husstedt and H. J. Schafer Synthesis 1979 964. " U. Husstedt and H. J. Schafer Synthesis 1979 966. Aliphatic Compounds -Part (i) Hydrocarbons Markovnikov hydrohalogenation of alkenes is readily achieved in nearly quanti- tative yields under phase-transfer conditions at 80-1 15 "C using aqueous hydro- chloric hydrobromic and hydriodic The cis-hydroxylation of unsaturated substrates (including alkynes) by osmium tetroxide has been reviewed,34 and a procedure for the hydroxylation of sterically hindered alkenes uses trimethylamine N-oxide with pyridine as the oxidizing system in an osmium-tetroxide-catalysed reaction.35 A catalytic epoxidation process using hexafluoroacetone and hydrogen peroxide is an attractive alternative to peroxy-acid methods.2-Hydroperoxyhexafluoropro-pan-2-01 (5) is the effective reagent and disodium hydrogen phosphate in refluxing 1,2-dichloroethane acts both as a buffer and as a dehydrating agent to regenerate (5)from hydrogen peroxide and the hydrate of hexaflu~roacetone.~~ Novel applications of boron compounds in alkene chemistry continue to appear. Borane-1,4-oxathian (6),obtained by passing diborane into 1,4-oxathian at 250 "C hydroborates alkenes rapidly to trialkylboranes in excellent yield.37 An excess of the reagent can be oxidized with aqueous sodium hypochlorite to the sulphoxide which is readily extracted into an aqueous phase and the organoborane which is unaffected by this treatment can be used in the organic phase.Carbonylation of B-alkyl-9-borabicyclo[3.3. llnonanes and reduction of the intermediate provides a high yield stereospecific synthesis of the homologous borane as shown in Scheme 9.38Straight-chain alkyl groups can be lengthened by one carbon atom and some cyclic alkenes for example norbornene give cycloalkylmethyl derivatives which are unobtainable by normal hydroboration procedures. i-iii R-B Reagents i,,CO Li(MeO),AlH; ii LiAIH,; iii CH,SO,H Scheme 9 Thexylborne (thexyl = t-hexyl) is not a suitable reagent for producing dialkyl(thexy1)boranes that contain different unbranched primary alkyl groups but now it is possible to produce mixed dialkyl(thexy1)boranes by using thexylchloroborane in two ways (Scheme 10).In one procedure the alkyl(thexy1)chloroborane (7) reacts with a primary organolithium or Grignard reagent39and in the other (7) is reduced to alkyl(thexy1)borane in the presence of another alkene.40 The dialkyl(thexy1)boranes can then be transformed into the 33 D. Landini and F. Rolla J. Org. Chem. 1980 45 3527. 34 M. Schroder Chem. Rev. 1980,80 187. 3s R. Ray and D. S. Matteson Tetrahedron Lett. 1980 21 449. 36 A. J. Biloski R. P. Heggs and B. Ganem Synthesis 1980,810. '' H. C. Brown and A. K. Mandal Synthesis 1980 153. H. C. Brown T. M. Ford and J. L. Hubbard J. Org. Chem. 1980,454067. 39 G. Zweifel and N. R. Pearson J. Am. Chem. Sac. 1980,102 5919. 40 S. U.Kulkarni H. D. Lee and H. C. Brown J. Org. Chem. 1980 45 4542. 114 K. J. Toyne ii R' R' R' BH2 -yB:" -\ CI c1 \ R2 R2 (7) Reagents i HCI ether; ii alkene; iii RZM (M = Li or MgX)39or potassium tri-isopropoxyborohydride alkene;40 iv NaCN; v (CF,CO),O or PhCOCl vi NaOH H,O Scheme 10 corresponding ketones so that a general conversion of two different alkenes into the corresponding ketone is available for the first time.40 The conversion of a terminal alkene (RCH=CH2) into an aldehyde (RCH,CHO) has been achieved previously by hydroboration with the borane-dimethyl sulphide complex followed by oxidation with pyridinium chlorochromate (Py.HC1CrO3). There were certain limitations to this procedure which have now been largely overcome by using disiamylborane [bis-(3 -methyl-2-butyl)borane] as the hydrobor- ation reagent and a selective reaction that affects only the terminal double-bond in dienes is now possible.41 The less common reactions of alkenes include three different kinds of addition to produce amino-compounds.One of these provides the first general method for the direct conversion of alkenes into primary vicinal diamines and it uses the reaction of cyclopentadienylnitrosylcobalt dimer to give an adduct which can be reduced directly to the amino-containing product (Scheme 1lh4*Another procedure 0 II R' / R3 \ / N-CR'R~ ii R2-c-c-cp-co-\ I I + I I R4 H2N NH2 R3/'/T N-CR3R4 R' II \/ 0 c=c /\ R2 K' K- R' R3 PhCN I/ R;N -c-c I-pd -CI 5 R3N -c I-CI -0AC II II ~2 ~4 \ PhCN R2 R4 (8) Reagents i [(Cp)Co(NO)], THF NO; ii LiAlH, THF; iii [(PhCN),PdCI,] THF; iv R',NH THF; v N-bromosuccinimide or Pb(OAc) or Br, MeC0,H Scheme 11 achieves direct stereospecific oxyamination of an alkene to a vicinal amino-alcohol derivative e.g.an acetate (8),as also shown in Scheme 11.43 A P-amino-palladium complex is readily obtained from an alkene and oxidative cleavage of the palladium- carbon bond in the presence of an oxygen-containing nucleophile gives the amino- alcohol derivative in a 'one-pot' reaction. The reaction proceeds by overall cis-addition as a result of trans-aminopalladiation followed by an inversion of configur- ation in the oxidative substitution reaction. Primary amines did not give the 41 H.C. Brown S. U. Kulkarni and C. G. Rao Synthesis 1980 151. 42 P. N. Becker M. A. White and R. G. Bergman J. Am. Chem. SOC.,1980 102,5676. 43 J. E. Backvall and E. E. Bjorkman J. Org. Chern. 1980,45 2893. Aliphatic Compounds -Part (i) Hydrocarbons 115 N-(alky1)amino-alcohols,but these compounds could be prepared by a modified route [using N-(alkyl)benzylamine followed by debenzylation]. Finally terminal alkenes R2CH=CH2 have been used to alkylate secondary amines (R'CH2),NH in the presence of [Nb(NMe,),] or [Ta(NMe2)5] at 160-200 "C although in some cases the yields are rather low and the reaction fails with primary or tertiary amine~.~~ The 2-position of the alkene is linked to the a-carbon of the secondary amine to give R'CH2NHCHR'CHR2Me.A simple general method for preparing P-hydroxy-selenides in excellent yields uses the reaction of phenylselenenyl chloride (PhSeC1) with alkenes in aqueous acetonitrile at room temperature; the phenylseleno-group adds to the less- substituted carbon atom of the do~ble-bond.~ Terminal alkenes react with chloroiodomethane in a free-radical addition to give 1-chloro-3-iodo-alkanes and the subsequent reaction of these products with malon- ate esters gives a mixture of esters arising either from elimination of hydrogen iodide and substitution of the chloro-group or from the usual cyclization of malonate esters with 1,3-dihalogeno-a1kanes (Scheme 12).46With different experimental conditions either of these products can be obtained preferentially and the olefinic product can be used for the synthesis of y6-unsaturated acids or y-lactones.Several general guidelines have been presented to enable predictions to be made of the rate and orientation of free-radical additions to alkene~.~~ R 'CH=CHCH2CH2CO2H R'CH=CH2 iii-v 9 / \.L R 'CH=CHCH2CH(C02R2)2 R'CHICH2CH2CI + wi 0 Reagents i CH2CII azobisisobutyronitrile at 80 "C;ii CH2(C02R2), R20Na R'OH; iii KOH; iv H'; v heat; vi KOH; vii aq. H,SO, reflux Scheme 12 Further Lewis-acid-catalysed additions to alkenes have been reported this year. Last year the reactions of methyl propiolate with alkenes were discussed,'ob and in a continuation of that work the reactions of alkenes with methyl chloropropiolate dimethyl acetylenedicarboxylate and methyl a-halogeno-acrylates have been studied.Ene reactions and/or stereospecific [2 + 21 cycloadditions occur with the first two (using ethylaluminium dichloride as catalyst) and the ene adducts and the cyclobutenecarboxylates (9) that are derived from methyl chloropropiolate undergo substitution reactions with organocuprates and can also be hydrolysed to P-keto-esters and substituted dimethyl glutarates (lo) respectively. When methyl 44 M. G. Clerici and F. Maspero Synthesis 1980,305. 45 A. Toshimitsu T. Aoai H. Owada S. Uemura and M. Okano J. Chem. SOC.,Chem. Commun. 1980 412. 46 S. Miyano H. Hokari Y. Umeda and H. Hashimoto Bull Chem. SOC.Jpn. 1980,53,770. 47 J. M. Tedder and J. C. Walton Tetrahedron 1980,36 701. B. B. Snider D. M. Roush D.J. Rodini D. Gonzalez and D. Spindell J. Org. Chem. 1980,45,2773. 116 K. J. Toyne R4 c1 R2 9.02Me R3.JT( Rz CHzC02Me ~1 C0,Me R' (9) (10) a-chloroacrylate is used a stereo- and regio-selective ene reaction occurs in which the new C-C bond is formed exclusively at the less-substituted carbon atom of the alkene and the hydrogen is transferred from the alkyl group that is syn to the alkenyl hydrogen (Scheme 13).49Good yields of ene adducts are obtained with 1,l-disubstituted and trisubstituted alkenes and the a-chloro-esters that are produced are useful synthetic intermediates. :cR3 CH2R2 Rt. .c=c.-.CH2R2 H' 'CH2R3 c1 CO2Me Reagents i H,C=CCICO,Me EtAlCI, C,H Scheme 13 Ene reactions of alkenes and aldehydes have been achieved for the first time with dimethylaluminium chloride which acts as a catalyst and prevents any proton- initiated rearrangements by producing methane and a non-acidic aluminium alkoxide from the initial product (1 1) (Scheme 14).50 The reaction therefore gives a route to homoallylic alcohols from alkenes; by using formaldehyde alk-3-en-1-01s can be prepared.Diethyl oxomalonate has been used as an enophilic reagent with mono- di- and tri-substituted alkenes to give an overall reaction which is equivalent to an ene reaction of carbon dioxide (Scheme 14).51 The a-hydroxymalonic ester intermediate C02H R R Reagents i RCHO ArCHO or CHzO Me,AICI CH,Cl,; ii pH4 phosphate buffer; iii diethyl oxomalonate at 145-180°C; iv aq. KOH;v HCI; vi NaIO, pyridine or cerium@/) ammonium nitrate Scheme 14 49 B.B. Snider and J. V. DunEia J. Am. Chem. SOC.,1980 102,5926. 50 B. B. Snider and D. J. Rodini TetrahedronLett. 1980 21 1815. 51 M. F.Salomon S. N. Pardo and R. G. Salornon J. Am. Chem. SOC.,1980,102,2473. Aliphatic Compounds -Part (i)Hydrocarbons was hydrolysed to the diacid and then oxidized to the @?-unsaturated acid. Lower reaction temperatures can be used in a catalysed reaction and some reactions occur at or below room temperature when using tin(1v) chloride zinc(I1) chloride or mercury(I1) trifluoroacetate as catalyst. A new four-carbon annelation of alkenes offers easy access to a variety of cyclohexenones and the sequence is complementary to reactions such as Diels- Alder and Robinson annelations (Scheme 15).s2 2,2,6-Trimethyl-1,3-dioxolenone (12) readily prepared from diketen and acetone undergoes a photochemical [2 + 21 cycloaddition to an alkene and mild reduction of the photo-product (13) gives a hemiacetal which spontaneously loses acetone and then fragments to form a keto- aldehyde.Treatment of the keto-aldehyde with toluene-p-sulphonic acid in benzene and azeotropic removal of water gives the cyclohexenone. R’ i n (13) / R4 R4 Reagents i hv hexane; ii di-isobutylaluminium hydride; iii p-MeC6H4S03H C6H6,heat Scheme 15 Alkane- and arene-sulphonyl iodides add to alkenes using copper(I1) chloride as catalyst to give @-iodo-sulphones e.g. BuCHICH2S02R (or Ar) which can be dehydroiodinated to produce ap-unsaturated sulphones (E)-BuCH=CHS02R (or AT).^^ Some of these vinylsulphones may be useful dienophiles in Diels-Alder reactions.3 Dienes Symmetrical (E,E)-1,3-dienes have been prepared from terminal alkynes by the hydroboration sequence shown in Scheme 16 which does not require the isolation of any borane precursor and which gives only small amounts of mono-ene impurities arising from alkyl-group tran~fer.~~ The dienes are formed with retention of the configuration of the alkenylborane and (Z,Z)-1,3-dienes have also been prepared from (1Z)-1-alkenyldicyclohexylboranes. A palladium-catalysed decarboxylative elimination of the adducts from enals and carboxylate enolates presents a highly stereocontrolled synthesis of 1,3-dienes that has high or exclusive preference for the formation of an E-double-bond without affecting the stereochemistry of the double- bond that is present in the precursor (Scheme 17).55 52 S.W. Baldwin and J. M. Wilkinson J. Am. Chem. SOC., 1980 102 3634. s3 L. K. Liu Y. Chi and K. Jen J. Org. Chem. 1980 45 406. 54 J. B. Campbell and H. C. Brown J. Org. Chem. 1980,45 549. ss B. M. Trost and J. M. Fortunak J. Am. Chem. SOC., 1980,102,2841. 118 K. J. Toyne B(Sia) H CH,CH=CH H R' H \/ vii \ / \/ c=c -* c=c H ,c=c\ /\ R'/\H R' H ,c=c\\ H (15) R' H Sia = CHMeCHMe2 Reagents i 9-borabicyclo[3.3.1]nonane or dicyclohexylborane; ii NaOMe; iii CuBr.SMe, at 0 "C; iv CuBr-SMe at -15 "C; v H,C=CHCH,Hal (Hal = Br or I) at -15 to +25 "C; vi HB(Sia),; vii H,C=CHCH,Br [Pd(PPh,),] C,H, aq.NaOH Scheme 16 H OAc . .. R2 iii R -R1-R2 c0,-Reagents i R'CHCO,-;'ii MeCOCl; iii [Pd(PPh,),] Et,N toluene at 85 "C Scheme 17 Three procedures have been reported for the preparation of 1,4-dienes from alkynes. One of these is linked to the synthesis of 1,3-dienes mentioned above (Scheme 16) in which an alkenylcopper derivative is a proposed intermediate. At -15 "C the formation of the symmetrical conjugated diene is slow and addition of ally1 bromide leads to a (4E)- 1,4-diene (Scheme 16).56 The reaction sequence has also been used for internal alkynes and for the synthesis of (42)-1,4-dienes. A similar report describes the use of the reaction of alkenyl-9-borabicyclo[3.3. llnonanes with methylcopper and allylic halides to give the (4E)- 1,4-dienes but the reaction using alkenyldisiamylboranes leads to the dime^-.^' Dialkenylchloroboranes (14) were also used to form 1,4-dienes by their reaction with methylcopper at -30 to -40 "C followed by cross-coupling with allylic halides; the cross-coupling reaction of (14) with simple alkyl halides in the presence of PhSLi or triethyl phosphite gave an alkene.57 1-Alkenyldisiamylboranes (15) are also readily obtainable from alk- 1-ynes and they undergo a palladium-catalysed cross-coupling with allylic bromides to produce c1 (14) 56 H.C. Brown and J. B. Campbell J. Org. Chem. 1980,45,550. 57 H. Yatagai J. Org. Chem. 1980 45 1640. Aliphatic Compounds -Part (i) Hydrocarbons 119 1,4-dienes stereoselectively (see Scheme 16).58 Alkenylboranes and palladium acetate can react to give products by intramolecular migration protonolysis or cross-~oupling.~~ With (E)-alkenyldialkylboranes from terminal alkynes intramolecular migration gives (E)-alkenes whereas the alkenylboranes from inter- nal alkynes undergo protonolysis to produce (2)-alkenes; the alkenylpalladium intermediates can be trapped by allylic chlorides to give 1,4-dienes.The coupling of lithium acetylides and allylic halides to give 1,4-enynes is improved by the addition of lithium iodide and the ratio of a-and y-coupling products is approximately 95 :5;60the enynes can then be used to give 1,4-dienes. A two-step sequence has been developed to convert an alk-1-yne into a 1,5-enyne (Scheme 18).61 The method allows 1,5-dienes to be obtained directly by using homoallylzinc chloride [H2C=CH(CH2)2ZnC1] or indirectly by reduction of the enyne (16).Repetition of the sequence leads to long-chain 1,5-diene units and this facility should prove useful in terpenoid synthesis. Me I Me CH,CH,C=CH ... \/ RCGCH 'J'b \c=c/ iii,iv - R/ 'H Reagents i Me,AI [(Cp),ZrCI,] (CH,Cl),; ii 12 THF; iii [Me,SiC~C(CH,),ZnCI] [Pd(PPh,),] THF; iv KF.2H20 DMF Scheme 18 4 Alkynes Synthesis.-A simple and mild preparation of alkynes uses solid potassium t- butoxide and catalytic amounts of 18-crown-6 in petroleum ether.62 1,2-Dibromides (from terminal alkenes) and 1,l-dichlorides (from aldehydes) give terminal alkynes and internal geminal dihalides (from symmetrical ketones) give internal alkynes (Scheme 19) whereas 2,2-dichlorides (from methyl ketones) only give alk-1 -ynes if I I RCHBrCH2Br __* RCeCH c-RCH2CHC12 I RCH2CC12CH2R __* RCrCCH2R Reagents i KOBu' 18-crown-6 light petroleum at 60-100 "C Scheme 19 the 3-position is blocked.The second stage of these reactions involves dehy- drohalogenation of a halogeno-alkene and an alternative preparation of l-bromo- alkenes which could then be used to give terminal alkynes employs a Wittig reaction of an aldehyde with bromomethylenetriphenylphosphorane(Ph3P=CHBr) which is formed from triphenylphosphine and dibr~momethane.~~ N. Miyaura T. Yano and A. Suzuki Tetrahedron Lett. 1980 21 2865. ''H. Yatagai Bull. Chem. SOC.Jpn. 1980,53 1670. 60 H.Yatagai Y. Yamamoto and K. Maruyama Chem. Lett.. 1980,669. 61 E. Negishi L. F. Valente and M. Kobayashi J. Am. Chem. SOC.,1980 102 3298. 62 E. V. Dehmlow and M. Lissel Liebigs Ann. Chem. 1980. 1. 63 M. Matsumoto and K. Kuroda Tetrahedron Lett. 1980 21,4021. 120 K. J. Toyne Enol phosphates (17) are readily formed from methyl ketones; on @-elimination with a strong base the phosphates (17)give the terminal alkyne (Scheme 20).64This procedure represents the first general method for converting methyl ketones into terminal alkynes. I I1 RCOCH3 RC=CH2 RC=CH I OPO(0Et)z (17) Reagents i lithium tetramethylpiperidide CIPO(OEt),; ii lithium tetramethylpiperidide aq. HCI Scheme 20 Aldehydes (R'CHO) can be readily converted into 1,l -difluoro-alkenes (R1CH=CF2) by using dibromodifluoromethane and triphenylphosphine in the presence of zinc dust.The difluoro-alkenes will then react with alkyl-lithiums (R2Li) either in THF to give internal alkynes R'C=CR2 or in ether to give a monofluoro- alkene R'CH=CFR2 from which the alkyne can be generated by reaction with lithium di-i~opropylamide.~' In several cases however the alkyne is contaminated with a small amounbof allenic product. Reactions of A1kynes.-A review on the formation of copper and silver organo- acetylides and their uses in organic synthesis has appeared.66 Three papers report some reactions of 1,3-dilithio-alk- 1-ynes with various elec- trophiles (see also ref. 1Oc). In almost all cases epoxides benzyl chloride and trimethylchlorosilane have been found to react exclusively on the propargylic site to give (18) (Scheme 21).67 It appears that the terminal alkyne function is RCGCH R1CH(OH)CH2CH20H R'CHXCGCH (18) x = CH~CHR'OH CH2Ph,or SiMe3 Reagents i THF BuLi-hexane at -30°C and then at 20-30"C6' or BuLi-hexane at -2O"C for 16-24 h;68 ii BuLi ether at -20 "C and then at room temperature for 30 h;69iii BH, THF; iv HzO NaOH; v H,O,; vi BD3 THF; vii COz slurry in hexane; viii \RZ or PhCH,CI or Me,SiCI as appropriate 0 Scheme 21 conveniently protected by lithium and that the relative nucleophilicities of positions 1 and 3 are determined by their basicities.The reaction of the dilithio-compound with formaldehyde and cyclic ketones occurs at both C-1 and C-3 to give alk-2-yne- 1,5-diols but with carbon dioxide the allene- 1,3-dicarboxylic acid is produced.68 The dilithio-derivatives have also been prepared from the alk-2-ynes and sub- 64 E.Negishi A. 0.King W. L. Klima W. Patterson and A. Silveira J. Org. Chem. 1980 45 2526. 65 S. Hayashi T. Nakai and N. Ishikawa Chem. Lett. 1980 935. 66 A. M. Sladkov and I. R. Gol'ding Russ. Chem. Rev. (Engl. Trans.),1979 48 868 (Usp. Khim. 1979 48 1625). 67 H. Hommes H. D. Verkruijsse and L. Brandsma Red. Trav. Chim. Pays-Bas 1980 99 113. K. A. Pover and F. Scheinmann J. Chem. SOC.,Perkin Trans. 1 1980 2338. Aliphatic Compounds -Part (i) Hydrocarbons 121 sequent hydroboration-oxidation gives a convenient method for the exclusive formation of 1,3-diols (Scheme 21).69 Terminal alkynes react with carbon monoxide and an alcohol under mild condi- tions to give acetylenecarboxylates R'CGCCO~R~.~' The reaction is catalysed by palladium dichloride and a stoicheiometric amount of copper(r1) chloride is used to regenerate the catalyst.A new synthesis of 2-bromo-alk-1-enes in high yield is accomplished by direct 'Markovnikov' hydrobromination of alk-1-ynes with tetraethylammonium hydro- gen dibr~mide.~~ A solution of tetraethylammonium bromide in dichloromethane absorbs the hydrogen bromide that is required for the addition and the bromide can subsequently be recovered. Zinc-copper couple in boiling methanol reduces alkynes to alkenes in nearly quantitative yield. Terminal alkynes give alk- 1-enes and internal alkynes give (Z)-alkenes without any trace of the (E)-i~omer.~~ A new and potentially powerful method for the synthesis of specifically substituted alkenes from internal alkynes has been demonstrated using but-2-yne (Scheme z).'~ The alkyne complex (19) is attacked by nucleophiles to give (20) and the alkenyl group can be cleaved by halogen with retention of stereochemistry.When the nucleophile is hydride ion (20) can be isomerized to (21) and then cleaved. Ae NU Me F MeJ Fe*. Me Br Me (19) (20) iiil [Nu= HI H Me \/ C ii 'C/ -H II Me II C C /\ /\ Fe* = (Cp)Fe(CO)(PPh3); Fe* Me Br Me Nu = H SPh SBu OEt CN CzCH or CH(C02Et)2 (21) Reagents i Nucleophile; ii Br, ether at -78 "C; iii toluene at 40 "C Scheme 22 (E)-Alkenyl-pentafluorosilicates(22) (see ref.10d) react with alcohols R30H in the presence of oxygen and catalytic amounts of copper(I1) acetate to give (E)-alkenyl ethers (23) of high isomeric purity; when R2 = H the reaction with water gives aldehydes R'CH2CH0.74 69 A. Medlik-Balan and J. Klein Tetrahedron 1980 36 299. 70 J. Tsuji M. Takahashi and T. Takahashi Tetrahedron Lett. 1980 21,849. J. Cousseau Synthesis 1980 805. 72 B. L. Sondengam G. Charles and T. M. Akam Tetrahedron Lett. 1980 21,1069. 73 D.L. Reger and P. J. McElligott J. Am. Chem. SOC.,1980 102,5923. 74 K.Tarnao T. Kakui and M. Kumada Tetrahedron Lett. 1980 21,4105. 122 K. J. Toyne R' R2 \/ c=c H OR^ (22) (23) 5 Allenes A general regioselective synthesis of allenes based on the alkylation of primary secondary or tertiary propargyl alcohols has been reported (Scheme 23).75The frequently used SN2'reaction between propargyl derivatives and an alkyl group in diorganocuprates is one of the most valuable methods for the synthesis of allenes (24) R' 1 \ C=C=CR2R3 R4' Reagents i MeLi ether; ii Cur THF at -70 "C; iii R4Li; iv [Bu",hN(Me)Ph] I- DMF at -70 "C Scheme 23 but it requires an excess of alkyl groups in the cuprate reagent and also propargyl derivatives which are not always readily accessible.The new procedure uses the readily accessible propargyl alcohol to give an organocopper intermediate and an excess of the alkyl-lithium is not required. Nucleophilic attack by the alkyl(methy1- pheny1amino)cuprate counter-ion on the y-carbon of the ion (24)gives the allene.With enyne alcohols however the coupling occurs on the olefinic carbon and conjugated (2)-enynes are formed predominantly [e.g. (25) gives mainly (26),using MeLi]. Et \ //C-H R'C=CCH(OH)CH= CH R'CrC-C (25) \ H (26) A further has appeared on the homologation of terminal alkynes to allenes using formaldehyde di-isopropylamine and copper(1) bromide in dioxan (see also ref. 10e). '' Y. Tanigawa and S. Murahashi J. Org. Chem. 1980,45,4536. 76 H. Fillion D. AndrC and J. Luche Tetrahedron Lett. 1980 21 929.