9 Aliphatic Compounds Part (i) Hydrocarbons ~~~~ ~ By K.J. TOYNE Department of Chemistry The University of Hull Hull HU6 7RX 1 Alkanes Two similar methods for the deoxygenation of alcohols to alkanes have been reported. Tertiary alcohols and sterically hindered secondary alcohols can be deoxygenated by reaction of their acetates with lithium in ethylaminel and esters of primary secondary or tertiary alcohols are reduced by sodium in hexamethyl- phosphoric triamide (HMPA) containing t-butyl alcohol2 (Scheme 1). The only significant side reaction in these convenient procedures is the regeneration of the initial alcohol. 0 0-R'OH -+ R~-C R2-C ' -+ R1. -+ R1H 'OR' 0-R' 1' R'O-+ R'OH Reagents i Li-EtNH or Na-HMPA-Bu'OH Scheme 1 The debromination of uic- dibromoalkanes to alkanes has been achieved using sodium hydrogen telluride prepared in situ (Scheme 2).3 The reaction proceeds via the alkene4 and sodium hydrogen telluride may therefore prove to be a useful reagent both for debromination of vic-dibromides and for the hydrogenation of alkenes.R1CHBrCHBrR22R'CH=CHR2 R'CH2CH2R2 Reagents i and ii Te-NaBH.,-EtOH Scheme 2 The transformation of aldehydes and ketones into alkanes can be achieved indirectly by reduction of the tosylhydrazones in various ways and now sodium borohydride-acetic acid has been shown to be a convenient alternative reagent R. B. Boar L. Joukhadar J. F. McGhie S. C. Misra A. G. M. Barrett D. H. R. Barton,and P. A. Prokopiou J.C.S. Chem. Comm. 1978,68. 'H.Deshayes and J.-P. Pete J.C.S. Chem. Comm. 1978 567. K. Ramasamy S. K. Kalyanasundaram and P. Shanmugam Synthesis 1978,545. K. Ramasamy S.K. Kalyanasundaram and P. Shanmugam Synthesis 1978,311. 159 160 K. J. Toyne which offers the advantage that migration of the double bond in &-unsaturated tosylhydrazones does not occur.' The use of sodium borohydride in polar aprotic solvents to achieve selective reductions of halides sulphonate esters tertiary amines and NN-disulphonimides has been summarized and a method is given for the preparation of hydrocarbons from alcohols by the conversion of alcohols into iodides followed by reduction in situe6 2 Alkenes Synthesis.-Several attractive routes have been reported for the synthesis of substi- tuted alkenes from alkynes.Terminal and internal alkynes react with organoalanes- zirconocene dichloride complexes [R32A1-C12Zr(C5H5)] to produce alkenyl metals (1) by stereospecific cis-addition (Scheme 3).' The Pd- or Ni-catalysed coupling MLn = A1R22or ClZr(C5H5)2 Reagents i RZ Al-C1zZr(C5H5)z; ii H'; iii R3X-Pd or Ni phosphine complex-ZnClz Scheme 3 reactions of (1)with alkenyl aryl or alkynyl halides are significantly promoted by metal salts such as zinc chloride and this discovery provides for the first time a general procedure for the synthesis of trisubstituted alkenes [(2);H(R') =HI.' With suitable choice of R3X a method is therefore available for the stereoselective and regioselective 'one-flask' conversion of terminal alkynes into conjugated dienes (R3=alkenyl) and enynes (R3=alkynyl).The 2-methylalkenylalanes (3)formed in these reactions from terminal alkynes and Me3AI-C12Zr(C5Hs)2 can be functional- ized in a variety of ways (Scheme 4),9 and this procedure offers a simple selective route to some terpenoids as illustrated by the synthesis of geraniol and ethyl geranate. The reaction of alkynes with trimethylalane-titanocene dichloride has also been reported but the reactions with internal and terminal alkynes have ' R. 0.Hutchins and N. R. Natale J. Org. Chem. 1978,43,2299. R. 0.Hutchins D. Kandasamy F. Dux C. A. Maryanoff D. Rotstein B. Goldsmith W. Burgoyne F. Cistone J. Dalessandro and J. Puglis J. Org. Chem. 1978,43 2259. D. E. Van Horn and E. Negishi J. Amer. Chem.Soc. 1978,100,2252. * E. Negishi N. Okukado A. 0.King D. E. Van Horn and B. I. Spiegel J. Amer. Chem. SOC.,1978,100 2254. N. Okukado and E. Negishi Tetrahedron Letters 1978,2357. A liphatic Compounds R H R H R H i\/ ii \ / \c=c / t c=c + c=c /\ / \-Me/ \C02CH2Me Me Al(Me)2 Me A1(Me)2Bun )i (3) R H a X=CH20H \/ b. X=C02H Me/c=c\x c X=CH20Me Reagents i ClCO,CH,Me; ii BunLi;iii (CH,O) or CO or ClCH,OMe Scheme 4 their limitations because of dehydrometallation or polymerization." However carbometallations of metal-substituted alkynes (e.g. RCzCZnC1) with Me3A1-Cl2Ti(C5H5) and subsequent hydrolysis gives the terminal alkene R(Me)C=CH,. Another convenient stereospecific route to tri-substituted alkenes involves suc- cessive reaction of a terminal alkyne with a Grignard reagent and a trialkylborane (Scheme 5)." The intermediate alkenyl iodide (4) can also be stereospecifically R H R H R H iii-v \C=C / -A \c=c / ___ \c=c / I/* RCECH R H \c=c / Reagents i R'MgBr-CuBr,Me,S; ii I,; iii Bu"Li; iv R23B; v I,; vi RZMgX,Pd(PPhJ4; vii electrophiles Scheme 5 cross-coupled in a palladium-catalysed reaction with a variety of Grignard reagents to give tri-substituted alkenes (by using alkylmagnesium halides) or 1,3-dienes (by using alkenyl magnesium halides).I2 When methylmagnesium bromide was used in the first stage of the sequence the product was hydrolysed to a terminal alkene [(S); R' = MeE =HI or was treated with ally1 bromide or acetyl chloride to produce 1,4-dienes or a@-unsaturated ketones re~pectively.'~ Terminal and internal alkynes have been reduced stereoselectively by MgHz-CuI or MgH2-CuOBu' to terminal alkenes and cis-alkenes respectively without formation of alkane or tr~ns-alkene.'~ cis-Alkenes have also been obtained from lo D.E. Van Horn L. F. Valente M. J. Idacavage and E. Negishi J.Orgunometullic Chem. 1978,156,C20. N. J. LaLima and A. B. Levy J. Org. Chem. 1978,43,1279. l2 H. P. Dang and G. Linstrumelle Tetrahedron Letters 1978 191. l3 A.Marfat P. R. McGuirk and P. Helquist Tetrahedron Letters 1978 1363. l4 E.C.Ashby J. J. Lin and A. B. Goel. J. Org. Chem. 1978 43,757. 162 K. J. Toyne internal alkynes by reaction with a dialkylborane followed by palladium diacetate- catalysed protonolysis of the intermediate alkenyldialkylborane (Scheme 6 ;X = R’).’’ In this sequence terminal alkynes behave in a completely different manner to give trans-alkenes.The reduction of alkynes and alkenes with lithium aluminium hydride mixed with transition metal halides in catalytic or equimolar amounts has been studied in detail and the reagent LiA1H4-NiCl2 (1:0.1) is particularly usefu1.16 Alkynes can be reduced quantitatively to alkanes or using milder reaction condi- tions to alkenes. R H \/ R H/c=c\R i\ /x RCZCX-C=C H/ \BR22 a R R’ \/ X=HorR’ c=c H/\H Reagents i R2,BH; ii Pd(OAc),-Et,N-THF; iii Pd(OAc),-THF Scheme 6 Several syntheses of alkenes based on ketone precursors have been reported. Titanium metal freshly prepared from anhydrous titanium(II1) chloride by reduction with magnesium or potassium in anhydrous THF reduces enol phosphates to alkenes and so provides a regioselective conversion of ketones (not conjugated to aromatic rings) into a1kenes.l’ This method of reduction gives higher yields than that using Li-EtNH and the method may be particularly useful for the synthesis of 1,3-dienes from ap-unsaturated ketones.The lithium derivative of the intermediate formed from the reaction of an a-chloroketone and a Grignard reagent decomposes to give an alkene (Scheme 7). This sequence therefore provides a convenient ‘one-flask’ synthesis of alkenes and with a double bond present in the Grignard reagent it should allow the synthesis of dienes with the double bonds in predetermined positions.l8 Is H. Yatagai Y. Yamamoto and K. Maruyama J.C.S. Chem. Comm. 1978,702. l6 E. C. Ashby and J. J. Lin J. Org. Chem. 1978,43,2567. ’’S. C. Welch and M. E. Walters J. Org. Chem. 1978,43,2715. J. Barluenga M. Yus. and P. Bernad J.C.S. Chem. Comm. 1978 847. Aliphatic Compounds 163 @-Hydroxysulphides (RCHSPh.CHOHR') readily prepared from carbonyl compounds and a-lithiosulphides undergo reductive trans-elimination on treatment with 1-ethyl-2-fluoropyridiniumtetrafluoroborate and lithium iodide to give alkenes (RCH=CHR') under mild condition^.'^ The synthesis of terminal alkenes by an elimination reaction is frequently complicated by the simultaneous formation of substitution products and isomeric alkenes.A novel regiospecific route to obviate these problems uses the trityl carbonium ion to abstract a hydride ion from the @-carbonof an alkyl-iron compound {prepared by reaction of a bromide or tosylate with [CSH5Fe(CO),]-Na') and subsequent liberation of the alkene from the complex (Scheme 8)." v5-CSHSF~(CO)~CHRCHR~[v5-CSH5Fe(C0)2(RCH=CR2)]+BF4-'kRCH=CRz Reagents i Ph,C+BF,-; ii NaI-Me,CO Scheme 8 Terminal alkenes can also be converted into terminal alkenes with the carbon chain increased by three atoms in an attractively simple and general method based on hydroalumination (Scheme 9).21 Hydroalumination of alkenes gives organo- aluminium compounds which can be coupled by an SN2' pathway with allylic halides in a copper(1) halide catalysed reaction.All four alkyl groups on aluminium can participate and when 3-haloprop-1 -ene is used the chain-lengthening procedure shown in Scheme 9 (Reactions i and ii) is possible. Dienes react selectively at the less RCH~CHZCH~CH=CH~ /2-/ * RCHzCHzCH2CrCH RCH=CHz 4 (RCHzCH2)4A1Li RCH2CH2CH=C=CHz RCHZCHzHal Reagents i LiAlH,-TiCl,? ii CH,=CHCH2Hal-CuC1; iii CH,=C=CHBr-CuCl; iv CHrCCH2Br- CuCl; v CuCl or CuBr Scheme 9 substituted double bond and so in conjunction with substituted allylic halides the route may prove very useful for the synthesis of complex molecules. This procedure can be regarded as an extension of an important synthetic method for alkenes which is based on the regio- and stereo-selective coupling reactions of various allyl alcohol derivatives with Grignard reagents.However in the latter reactions complications frequently arise from allyl transpositions. A highly regioselective coupling of certain Grignard reagents with allyl 2-pyridyl ethers in the presence of magnesium bromide is now possible.22 It is suggested that the intermediate complex (6)is involved and most simple primary allyl pyridyl ethers in THF are alkylated selectively without rearrangement (Path A for unhindered ethers) whereas secondary and tertiary allyl l9 T. Mukaiyama and M. Imaoka Chem. Letters 1978,413. 2o D.E.Laycock and M. C. Baird Tetrahedron Letters 1978 3307. 21 F.Sato H. Kodama and M. Sato J. Organometallic Chem. 1978,157,C30. 22 T. Mukaiyama M. Yamaguchi and K.Narasaka Chem. Letters 1978,689. 164 K.J. Toyne (6) ethers in benzene react regioselectively with rearrangement (Path B). Direct alkyl- ation of allylic alcohols can be achieved with RCu:BF3 and this represents the first direct displacement of a hydroxyl group by an alkyl group using an organocopper reagent.23 The major product arises from allylic rearrangement. Several examples have been reported of the use of titanium derivatives in alkene-forming reductions. Reduction with titanium(II1) chloride and potassium lithium or a zinc-copper couple gives active titanium metal which is an efficient reagent for coupling ketones and aldehydes to produce alkenes [2RR'(H)CO + RR'(H)C=CRR'(H>].*" Intermolecular coupling works best with identical carbonyl groups but certain mixed products can be prepared e.g.with a diary1 ketone and another carbonyl system. Intramolecular coupling of dicarbonyls works well and rings of 4-16 and 22 carbon atoms have been prepared in high yield. The reaction involves a pinacol dianion intermediate and therefore active titanium metal can also be used for the deoxygenation of 1,2-diols. A titanium(II1) chloride-zinc powder induced coupling of pinacolone yields the new alkene trans-2,2,3,4,5,5- hexamethylhex-3-ene; some unusual chemical and physical properties of the compound have been rep~rted.'~ Titanium(II1) chloride-lithium aluminium hydride reductively couples allylic or benzylic alcohols and reduces epoxides and bromohydrins non-stereospecifically to alkenes.26 However two procedures for the stereospecific generation of alkenes from epoxides have appeared.In one method the epoxide is treated with methyl- triphenoxyphosphonium iodide in the presence of boron trifluoride ethe~ate,~' and in the second method trifluoroacetyl iodide and sodium iodide are used.28 Both procedures may involve an intermediate (7) which directly or via the intermediacy of an iodonium ion reacts with iodide ion to give the alkene. ox -.. I :' ;c-7LI (7) X = (Ph0)3PMe or CF3C0 A review of the usefulness of the intramolecular ene reaction in synthesis has been p~blished.~' 23 Y.Yamamoto and K. Maruyama J. Organometallic Chem. 1978,156 C9. 24 J. E.McMurry M. P. Fleming K. L. Kees and L. R. Krepski J. Org. Chem. 1978,43,3255. 25 D.Lenoir Chem. Ber. 1978 111,411.26 J. E.McMurry M. G. Silvestri M. P. Fleming T. Hoz and M. W. Grayston J. Org. Chem. 1978 43 3249. 27 K.Yamada S.Goto H. Nagase Y. Kyotani and Y. Hirata J. Org. Chem. 1978,43 2076. 28 P.E.Sonnet J. Org. Chem. 1978,43 1841. 29 W.Oppolzer and V. Snieckus Angew. Chem. Internat. Edn. 1978,17,476. Aliphatic Compounds Reactions.-Anti-Markovnikov hydrohalogenation of alkenes has been achieved in two ways. The readily available lithium tetra-alkylaluminiums from alk-1-enes react with copper(I1) chloride or bromide to give the corresponding 1-haloalkanes in good yield (Scheme 9; Reactions i and v).~’ Terminal alkenes react more readily than internal alkenes in the hydroalumination stage and so the method is parti- cularly useful for the preparation of 1-haloalkenes from non-conjugated dienes.The other procedure uses alkylpentafluorosilicates derived from hydrosilylation of an alk-1 -ene (Scheme lo).” Whereas tetraco-ordinated alkylsilanes are completely inert towards halogenolysis alkylpentafluorosilicatesreact extremely rapidly with halogens to produce the alkyl halide in good yield. iii RCH=CH2 4 RCH2CH2SiC13 K2[RCH2CH2SiF5]-RCH2CH2Hal Reagents i HSiC1,-H,PtCl,; ii KF; iii Hal Scheme 10 Several papers have developed the idea of allylic functionalization of alkenes by the formation of a C-C bond -a reaction which has its analogy with alkylation a to a carbonyl group. T-Allylpalladium complexes have been prepared from alkene~~~ and when their electrophilicity is increased by the addition of Iigands they react with ‘soft’ nucieophiles to give reaction at the ally1 position (Scheme 11).33,34The PdCl X = CHzCOzMe CHzCOR CHZSO~R CH2R CH2CH=CH2 \t WCO,Me Reagents i NaC1-PdC1,-NaOAc-HOAc-CuC12;ii phosphines or phosphites nucleophile Scheme 11 regioselectivity of the reaction depends on the nature of the attacking nucleophile and the structure of the m-ally1 complex but a preference normally exists for reaction at the less substituted carbon.Whereas methyl-lithium methylmagnesium iodide and lithium dimethylcuprate fail to give alkylation products successful alkylations have been achieved with the anions derived from malonate esters p-keto sulphones P-keto sulphoxides and P-keto sulphides and the types of alkylation shown in Scheme 11have been achieved.A new prenylation sequence has been devised which 30 F. Sato Y. Mori and M. Sato Chem. Letters 1978,833. 31 K. Tamao J. Yoshida M. Takahashi H. Yamamoto T. Kakui H. Matsumoto A. Kurita and M. Kumada J. Amer. Chem. SOC.,1978,100,290. 32 B. M.Trost P. E. Strege L. Weber T. J. Fullerton andT. J. Dietsche J. Amer. Chem. SOC.,1978,100 3407. 33 B. M. Trost L. Weber P. E. Strege T. J. Fullerton andT. J. Dietsche J. Amer. Chem. SOC.,1978,100 3416. B. M. Trost L. Weber P. E. Strege T. J. Fullerton and T. J. Dietsche J. Amer. Chem. SOC.,1978,100 3426. 166 K. J. Toyne allows the direct conversion of lower terpenes into higher terpenes by using the anion (8). Alkylation of a T-ally1,palladium complex followed by decarbomethoxylation and desulphonylation gives the prenylation product.Ultimately catalytic alkylation processes would be desirable but at least the transformation of the palladium chloride into palladium black allows the metal to be recycled. SO2Ph (8) Allylic functionalization has also been achieved by the three-step synthesis of allylic malonates from alkenes (Scheme 12).35The ene reaction of alkenes with hexafluorothioacetone generated in situ followed by reaction with dicar-bomethoxycarbene gives ylide (9) which rearranges and is then reduced to give the product. Reagents i [(CF,),CS]; ii N,C(CO,CH,),-CuSO,; iii Na-Hg Scheme 12 1-Phenylselenoalkan-2-ones(10)are readily prepared in high yield from terminal alkenes and are useful because they permit regiospecific alkylation at C-1 (Scheme 13,reactions i and ii).36 Reductive and oxidative removal of the phenylseleno-group SePh i-iii I RCH=CH2 -RCOCH2SePh 5RCOCHCH2R' /RCoCH2CH2R1 \ /(10) (11) \ RCOCH=CHR' [RCH(OSnBu&3€$SePh] Reagents i PhSeBr-EtOH; ii NaI0,-aq.MeOH; iii heat; iv Bu'OK-R'CH,X; v Et,N-PhSH; vi NaI0,-aq. MeOH; vii (PhSe)2-Br,-(Bu,Sn),0 Scheme 13 from (11) gives saturated ketones and ap-unsaturated ketones respectively (see Scheme 24 for a similar synthesis of ap-unsaturated ketones). The formation of (10) is thought to proceed via (12),which on oxidation and heating gives the vinyl ether (13). The eliminated phenylselenenic acid (PhSeOH) adds to (13) to give a hemi- acetal which is hydrolysed to (10).a-Phenylseleno carbonyl compounds (10) have '' B. B. Snider and L. Fuzesi Tetrahedron Letters 1978 877. 36 T. Takahashi H. Nagashima and J. Tsuji Tetrahedron Lettsrs 1978 799. Aliphatic Compounds OEt OEt I I RCHCH2SePh RC=CH2 (12) (13) also been prepared in a one-step process by using diphenyl diselenide bromine and hexabutyldistannoxane (Scheme 13; Reaction v)37 but the disadvantage of this approach is that appreciable amounts of the a-phenylseleno-aldehyde [RCH(SePh)CHO] are also produced. Phenylselenenic acid (PhSeOH) has been produced in situ from phenylseleninic acid (PhSe02H) and diphenyl diselenide (PhSeSePh) and reacts with trisubstituted alkenes by Markownikoff addition (Scheme 14).38 Oxidation of the p-hydroxy 0 OH SePh I R'R2C=CHCH2R3 A R'R2&-CHCH2R3 A (14) OH R' R2&CH=CHR3 Reagents i (PhSe),-H,02-MgS0,; ii Bu'OOH Scheme 14 phenylselenide (14)gives the unstable selenoxide which decomposes to the allylic alcohol and the complete 'one-flask' sequence represents a route from alkenes to rearranged allylic alcohols.The use of t-butyl hydroperoxide to oxidize (14) avoids the secondary epoxidation of the alkene product which can occur when hydrogen peroxide is used. Alkenes and alkynes are hydrometallated by magnesium hydride in the presence of a titanium catalyst [e.g. C12Ti(C5H5)]. The reaction is most satisfactory for monosubstituted alkenes which give nearly quantitative yields of the alkane after hydr~lysis;~~ (see also ref. 14). The formation of methyl ketones from terminal alkenes by oxidation with rhodium dioxygen complexes4o or combinations of rhodium trichloride and cupric perchlorate or nitrate41 has been reported and several papers and a book have appeared on the ozonolysis of alkene~.~~ Several workers have tried to distinguish between bridged and acyclic transition states for electrophilic additions to alkenes and alkynes.One approach uses the addition of arenesulphenyl chloride to alkenes and the hydration of alkenes as model 37 I. Kuwajima and M. Shimizu Tetrahedron Letters 1978 1277. 38 T.Hori and K.B. Sharpless J. Org. Chem. 1978,43,1689. 39 E.C.Ashby and T. Smith J.C.S. Chem. Comm. 1978,30. 40 F.Igersheim and H. Mimoun J.C.S. Chem. Comm. 1978,559. 41 H. Mimoun.M. M. P. Machirant and I. S. de Roch J. Amer. Chem. SOC.,1978,100. 5437. 42 (a)P.S. Bailey T. M. Ferrell A. Rustaiyan S. Seyhan and L. E. Unruh J. Amer. Chem. SOC.,1978,100 894;(b)P. S.Bailey and T. M. Ferrell J. Amer. Chem. Soc.,1978,100,899; (c) B.Mile and G.M. Morris J.C.S. Chem. Comm. 1978,263; (d) P.S. Bailey 'Ozonation in Organic Chemistry' Academic press New York 1978. 168 K. J. Toyne reactions involving bridged and acyclic rate-determining transition states respec- tively. These reactions are standards against which the structure-reactivity rela-tionship of other electrophilic addition reactions can be compared. The similarity in the structure-reactivity profiles of the addition of bromine and arenesulphenyl chloride indicates a bridged rate-determining transition state for both Another approach uses a series of compounds RMeC=CH2 and RHC=CMe2 (R=Me Et Pr" PhCH2 MeC02CH2 or CICH2) in an attempt to distinguish between a bridged and a carbonium ion-like transition state by internal comparison of the series and without resorting to external structure scales.The rate constants for bromination also lead to the conclusion that a bromonium ion pathway is The competitive nucleophilic attack of methanol and bromide ion on the inter- mediate bromonium ion has been used to study quantitatively the rapid second step in the bromination of alkene~.~'A series of methyl substituted ethylenebromonium ions give a mixture of bromomethoxyalkane and dibromoalkane in each case and the regio-selectivity and chemo-selectivity of the reaction can be correlated with charge distributions.The addition of bromine chloride to hex-1-ene and hex-1-yne in carbon tetra- chloride and methanol has been studied and an attempt has been made to distinguish between the bridged bromonium ion (15) the weakly bridged ion (16) and the open vinyl cation (17)in additions to hex-l-~ne.~~ A symmetrically bridged intermediate is believed to exist in the reactions of hex-1-ene and on the basis of small amounts of anti-Markownikoff products (in CCI,) or absence of cis-product (in MeOH) the reaction of hex-1-yne probably involves a very weakly bridged bromonium ion (16). (15) (16) (17) The acid-catalysed hydration of several isomeric Z/E-alkenes has been Surprisingly the value of the k(Z)/k(E)ratio for 1,2-di-t-butylethylene is much less than the values for additions involving bridged intermediates whereas one might have anticipated that the formation of the open ion in hydration would more effectively relieve strain present in the 2-isomer.However it is suggested that during protonation there is significant double bond character remaining and only in the fully formed intermediate is sufficient rotation possible to reduce the repulsion of the substituents. For reactions involving bridged transition states steric approach control is the decisive rate-determining factor. 3 Dienes Terminal 1,3-dienes can be prepared in a simple palladium-catalysed elimination of acetic acid or phenol from the readily available allylic acetates and allylic phenyl 43 G.H. Schmid and T. T. Tidwell J. Org. Chem. 1978,43,460. 44 E. Bienvenue-Goetz and J.-E. Dubois Tetrahedron 1978,34,2021. 45 J.-E. Dubois and J. R. Chrktien J. Amer. Chem. Soc. 1978,100,3506. 46 V. L. Heasley D. F. Shellhamer J. A. Iskikian D. L. Street and G. E. Heasley J. Org. Chem.. 1978,43 3139. 47 W. K. Chwang and T. T. Tidwell J. Org. Chern. 1978,43 1904. Alipha tic Compounds ethers re~pectively.~~ The allylic isomers give the same product in the same yield via a w-allylic complex (Scheme 15). R'CH2CH=CHCH20R (or R'CH2CHORCH=CH2) A R'CH=CH-CH=CH2 R = Ph or MeCO Reagents i Pd(OAc),-PPh Scheme 15 A method4' has been developed for the preparation of terminal 1,3-dienes which is similar in outline to that shown in Scheme 28 for allenes.1-Trimethylsilylallyl carbanion reacts with aldehydes and ketones to give a mixture of a-and y-products with the a-isomer predominating (Scheme 16). The crude mixture can be worked up in two ways to give the 1,3-diene. i,ii,iii HCH CH2=CHCH2SiMe3 -+ CH2 Reagents i Bu'Li; ii MgBr,; iii R'RZ(H)CO; iv SOCl,; v MeCOCI; vi Et4NF-MeCN Scheme 16 The importance of organometallic compounds in synthesis is well illustrated by the use of three different metals in distinct and very attractive stereospecific syntheses of substituted 1,3-dienes. The first involves the palladium-catalysed coupling of (E)-1-alkenylzirconium derivatives with alkenyl halides to give dienes of 297'/o isomeric purity (Scheme 17)." The second procedure involves the formation of a lithium dialkyl(trans-1-alkenyl)( 1-alkyny1)borate which on treatment with either boron trifluoride etherate or tri-n-butyltin chloride results in the preferential migration of the alkenyl group from boron to the adjacent alkynyl carbon atom.Protonolysis of the intermediate produced gives the 1'4-disubstituted (E,2)-buta- 1,3-dienes in good yields (Scheme 18; R2 must not be a tertiary alkyl gro~p).~' The method therefore offers a way of linking together two terminal alkynes in a predetermined way and should prove useful in natural product syntheses. Vinylmercurials are used in the third method (Scheme 19)52 to provide a route for the 'head-to-tail' dimeriza- tion of alkynes which complements an earlier procedure for the symmetrical 48 J.Tsuji T. Yamakawa M. Kaito and T. Mandai Tetrahedron Letters 1978,2075. 49 P. W. K. Lau and T. H. Chan Tetrahedron Letters 1978,2383. N. Okukado D.E. Van Horn W. L. Klima and E. Negishi Tetrahedron Letters 1978 1027. " G.Zweifel and S. J. Backluntl J. Organometallic Chem. 1978,156,159. '' R.C. Larock and B. Riefling J. Org. Chem. 1978,43 1468. 170 K. J. Toyne X R3 Reagents i H(Cl)Zr(C,H,),; ii 'C=C' (X = Br or I)-C12Pd(PPh3)z-Bui2AlH H/ 'R2 Scheme 17 R' H H R' iii iv \/ \c=c / Li+ L \c=c R2 /\ / \c=c / H \BR2-CrCR2 H c=c BR2 -.[". 1 H' \H Reagents i R,BH; ii R2C=CLi; iii BF3-ether or Bu3SnC1;iv MeCOzH Scheme 18 Reagents i catecholborane; Hg(OAc),; aq.NaC1; ii PdC12-Et3N-C6H6 Scheme 19 dimerization of vinylmercurials.The best results were obtained with 0.5 equivalents of palladium chloride but catalytic amounts can be used if anhydrous copper(r1) chloride is present as a reoxidant. @Unsaturated ketones react with dilithium carboxylates to give hydroxyacids which undergo decarboxylative dehydration under very mild conditions with dimethylformamide dimethylacetal and so provide a useful regiospecific route to lY3-dienes (Scheme 20).53 Even the unstable 1,3-diaryl-1,3-butadienescan be prepared by this method. Alkenylpentafluorosilicates,formed from terminal alkynes couple with allylic halides under the influence of a palladium catalyst to provide the regio- and stereo-isomerically pure (E)-1,4-diene (Scheme 21)54 (see also ref. 31).53 J. Mulzer U. Kiihl and G. Briintrup Tetrahedron Letters 1978,2953. 54 J. Yoshida K. Tamao M. Takahashi and M. Kumada Tetrahedron Letters 1978,2161. 171 Aliphatic Compounds R2 H R2 H R2 H -\/ i\/ ii \/ c=c +c=c c=c /\ H H/\CR’OH.CHR3C02H H/\C=CHR3 R’ /c=o R’/ Reagents i R3CH=C(OLi) from R3CH2C0,H-Pr’,NLi; ii Me,N.CH(OMe) Scheme 20 R RCECH A ‘C=C H / H iii R H \/ H/ H \CH2CH=CH2 Reagents i HSiCl,-H,PtCb; ii KF; iii CH,=CHCH,CI-Pd(OAc) Scheme 21 Two allylic groups have been linked regioselectively to produce the ‘head-to-tail’ 1,5 -dienes.” An allylic halide (R’CH=CHCH,Hal) regioselectively couples with a lithium ally1 boron ate complex (RCH=CHCH2BR32Li’) to form the 1,5-diene (R1CH=CHCH2CHRCH=CH2). 4 Alkynes Synthesis.-Alkynes are frequently prepared by alkylation of acetylene or alk-l- ynes or by elimination reactions but the methods are generally poor for alkynes with secondary tertiary or P-branched primary groups.A survey is reported of eight standard syntheses of internal or terminal alkynes containing one branched group and the best methods have been ~pecified.~~ A new synthesis which may be worth considering in conjunction with those discussed in the survey achieves the alkylation of terminal alkynes indirectly. The alkynes are converted into 1-bromoalk-1-ynes (R’C-CBr) which have been shown to react rapidly with trialkylalanes (R3Al) in the presence of catalytic amounts of bis(N- methylsalycila1dimine)nickel[Ni(me~al)~] to give the internal alkyne (R’CECR).’’ A method for increasing the chain length of terminal alkenes was shown in Scheme 9 (Reactions i and ii).21 Basically the same simple procedure can be modified to provide a general ‘one-flask’ route from alk-1 -enes to terminal alkynes containing three more carbon atoms (Scheme 9; Reactions i and iii).” The hydroalumination product of the alkene is coupled by an SN2‘pathway with bromopropadiene in the presence of catalytic amounts of copper(1) chloride to give terminal alkynes and it is possible to introduce the alkyne moiety selectively to one of the double bonds of a diene.Two new similar procedures for the preparation of mono- and di-substituted alkynes under mild conditions are based on the use of p-keto-sulphones which can 55 Y.Yamamoto and K. Maruyama J. Amcr. Chem. SOC.,1978,100,6282. 56 F. Bernadou. D. Mesnard and L. Miginiac J. Chem. Research (S),1978,106; J. Chem. Research (M) 1978,1501. ”G. Giacomelli and L. Lardicci TetrahedronLarters 1978,2831. 58 F. Sato H. Kodama and M. Sato Chem. Letters 1978,789. 172 K. J. Toyne be prepared in several ways.59,60 For example the lithium derivative of an alkyl aryl sulphone will react with a carboxylic acid derivative so that each reactant provides part of the ultimate alkyne (Scheme 22) or the P-keto-sulphone can be obtained Reagents i Bu"Li-RC0,Me or RCOCl; ii NaH-(EtO),POCI-THF-HMPA;iii Na-liq. NH or Na/Hg-THF-DMSO Scheme 22 from a ketone (RCOCH2R1) by enolate sulphenylation (or sulphinylation) followed by oxidation.The p-keto-sulphone is then converted into an enol phosphate from which the alkyne is produced by reductive elimination. The sequence has also been used for the preparation of conjugated enynenes (R = R' =alkenyl) and highly stereoselective routes to central-cis- and central-trans-conjugated trienes are now available.60 Another new synthesis of alkynes also starts with a carboxylic acid derivative (Scheme 23)6' and has superficial similarities to the sequence described above. NNHTos II MeLi RC02Li+R'CHLiSMe + RCOCHR'SMe + R-C-CHR'SMe RCrCR' Scheme 23 Reaction of a lithium carboxylate with a (methy1thio)methyl-lithiumderivative gives an a-sulphenylated ketone the toluene-p-sulphonylhydrazone of which decom- poses on treatment with methyl-lithium to give the alkyne.(Methy1thio)methyl- lithium (Scheme 23; R'=H) is used to give terminal alkynes in most of the published examples but the method should be suitable for the formation of a variety of alkynes. Reactions.-The reactions of alkynes and their derivatives frequently form the basis for the synthesis of alkenes and allenes (see appropriate section). In this part of the report other significant reactions of alkynes are considered. A mild regiospecific synthesis of trans-a$?-unsaturated ketones uses the reaction of trialkylalkynylborate salts with benzeneselenenyl chloride (Scheme 24).62Selec-tive oxidation at boron and subsequent oxidation at selenium gives (19) whereas oxidation of (18)with hydrogen peroxide gives the internal alkyne (RC=CCH,R').Homoallylic alcohols bearing tri-substituted olefinic groups can be prepared stereoselectively from the reaction of epoxides and a vinylcopper (Scheme 25).63 59 P.A. Bartlett F. R. Green and E. H. Rose J. Amer. Chem. Soc. 1978 100,4852. 6o B. Lythgoe and I. Waterhouse Tetrahedron Letters 1978,2625. 61 S. Kano T. Yokomatsu and S. Shibuya J. Org. Chem. 1978,43,4366. 62 J. Hooz and R. D. Mortimer Canad. J. Chem. 1978,56,2786. P. R. McCuirk A. Marfat and P. Helquist Tetrahedron Letters 1978 2465. Aliphatic Compounds R2B SePh 0 SePh [R3BC~CCH2R']Li+ '\/ -% \C-CH / R /'='\CH2R1 R / 'CH2R' (18) liii RCOCH=CHR' (19) Reagents i PhSeCl; ii H,O-Me,NO; iii H,Oz Scheme 24 R3 OH R*C=CH i -+ R' Cu(Me2S)MgBr:! R1 \CH-CH \ / ii-iv \ / H -/c=c\R2/C=C\H R2 / \R4 Reagents i R'MgBr-CuBr(Me,S); ii PrC-CLi; ,O\iii R3CH-CHR4; iv NH4Cl Scheme 25 Normally the reaction is slow but the vinylcopper can be activated by the addition of a lithium acetylide and with monoalkylated epoxides the only product results from reaction at the less substituted position.The use of phase-transfer reagents in the potassium permanganate oxidations of alkynes permits the formation of a-diones from internal alkynes; carboxylic acids are formed by oxidative cleavage of terminal alkyne~.~~ An improved method for the hydration of alkynes to ketones uses a mercury impregnated resin sulphonic acid catalyst which can be recovered and ~e-used.~' 5 Allenes A series of papers has clarified the confused area of the reactions of propargylic chlorides with Grignard reagents and dialkylcuprates.6648 In the absence of tran- sition metal impurities terminal propargylic chlorides (R12 CClCECH) react with Grignard reagents (RMgX) to form an allene carbene-ztvitterion intermediate (20) by proton abstraction of the acetylenic hydrogen by the Grignard reagent R12t-C% R12C=C=C: f* (20) followed by loss of chloride ion.66 Nucleophilic attack on this intermediate by a second molecule of Grignard reagent at either the propargyl or the allenyl carbon and subsequent hydrolysis produces a mixture of two alkynes (R',RCC=CH R',CH-CrCR) and an allene (R',C=C=CHR).D. G. Lee and V.S. Chang Synthesis 1978,462. " G. A. Olah and D. Meidar Synthesis 1978,671. ''D.J. Pasto R H. Shults J. A. McGrath and A. Waterhouse J. Org. Chem. 1978 43 1382. 174 K.J. Toyne However in the presence of catalytic quantities of transition metal salts (e.g. FeC13) Grignard reagents react with propargyl chlorides to produce allenes (Scheme 26).67The proposed mechanism involves the reaction of the Grignard reagent with 2RMgX+FeC13 + R2FeCl -P Fe'CI+R2 FeCI2 R / / + R',C=C=C /FeCIR + R'zC=C=C /R12C=C=C 'R2 \R2 \R2 R' CCICrCR2 + FeCl \ ii ii (21) R1,C(FeCI,)C~CR2 + R12C(FeCIR)CrCR2+ R1,RCC-CR2 Scheme 26 the metal salt to produce a low-valence state metal species which undergoes insertion into the carbon-chlorine bond of the propargyl chloride. Displacement of the chlorine bonded to the metal by an alkyl group from the Grignard reagent produces a species which undergoes thermal decomposition to produce the allene and regenerate Fe'CI.With primary and secondary alkyl Grignard reagents the allene is formed exclusively and only when the alkyl group of the Grignard reagent is methyl and the propargyl chloride is non-terminal is an appreciable amount of the alkyne formed. t-Butylmagnesium bromide is totally unreactive and this is probably due to steric hindrance in the formation of (21) and/or (22). The final paper of the series however presents a procedure by which t-butyl- allenes could be prepared.68 Dialkylcuprates react with propargyl chlorides to form allenes which arise by alkyl transfer from copper to the propargyl halide in a tr-complex (Scheme 27).The mixed n-butylmethyl- and t-butylmethyl-cuprates react to transfer preferentially the n-butyl and t-butyl groups respectively. R' Scheme 27 Three useful methods have been published for the synthesis of terminal allenes. In one of these the hydroalumination product of a terminal alkene is treated with 67 D. J. Pasto S.-K. Chou A. Waterhouse R. H. Shults and G. F. Hennion J. Org. Chem. 1978,43,1385. D.J. Pasto S.-K. Chou,E. Fritzen R. H. Shults A. Waterhouse andG. F. Hennion J. Org. Chem. 1978 43,1389. Aliphatic Compounds 175 3-bromoprop-1-yne in the presence of a catalytic amount of copper(1) chloride (Scheme 9; Reactions i and i~).~' This reaction represents a simple general method for the addition of an allene moiety to an alkene double bond and even sterically hindered alk-1 -enes react satisfactorily.Aldehydes and ketones can be converted into terminal allenes as shown in Scheme 28.70 The vinyl carbanion formed from a-bromovinyltriphenylsilane or a-bromo- vinyltrimethylsilane by metal-halogen exchange reacts with aldehydes or ketones to give (23). This hydroxy compound and other P-functionalized vinylsilanes [(24)and (25)] are surprisingly resistant to elimination but fluoride ion on (24) or (25) promotes elimination under mild conditions to give the allene uncontaminated with alkyne. The reaction via the chlorides is only suitable for aldehydes or diary1 ketones and the route via the trifluoroacetates is more suitable for aliphatic ketones. R'\ C-c=CH + isomeric /I I chlorides R2(H)C1 SiR k R'\ (24) R' \ C-C=CH / RZ[H)'~~ iiR3\ R2W) C=C (23) R' \ C-C=CH R2' I I OCOCF SiRJ (25) Reagents i SOCI,; ii (CF,CO),O-pyridine; iii F-in DMSO or MeCN Scheme 28 The third synthesis of terminal allenes also starts with a carbonyl group which is reacted with lithium diethyl phenylsulphinylmethylphosphonate to give the 1-alkenyl sulphoxide (26) (Scheme 29).71Methylation of the vinyl hydrogen of (26) gives (27),and the lithium derivative of (27) generates the allene.R'R2C=0 &R'R2C=CHSOPh AR'R2C=CMeSOPh (26) (27) 1 R' R2C=C=CH2 Reagents i (EtO),POCH,SOPh-BuLi; ii Pr',NLi-MeI; iii lithium 2,2,6,6-tetramethylpiperidide; iv NH4Cl Scheme 29 69 F.Sato K.Oguro and M. Sato Chem. Letters 1978,805.'O T. H. Chan W. Mychajlowskij B. S. Ong and D. N. Harpp J. Org. Chem. 1978,43 1526. "G.H.Posner P.-W. Tang and J. P. Mallamo Tetrahedron Letters 1978,3995;G.H. Posner and P.-W. Tang I. Org. Chem. 1978,43,4131. 176 K. J. Toyne Three further syntheses of allenes use propargyl ketones or propargyl alcohols as their starting material. The reduction of tosylhydrazones of @unsaturated ketones by catecholborane occurs with regiospecific migration of the double bond. With tosylhydrazones of conjugated acetylenic ketones the migration also occurs to produce allenes in good yield (Scheme 30).72 NNHTos II RC~C-CR' 4RCH=C=CHR' I1 Reagents i catecholborane; ii NaOAc,3H20 Scheme 30 In 1975 an efficient synthesis of allenes from prop-2-ynyl tosylates and organo- copper(1) compounds was reported which had the disadvantage that direct synthesis of tosylates from the tertiary alcohols is unsatisfactory.However sulphinic esters are readily available and it has now been shown that the sulphinate group can be substituted by organocopper(r) reagents (Scheme 3 1).73 The stereochemistry of the reaction in one example was shown to be syn-1,3-substitution arising from a stereospecific substitution by the copper species followed by a 1,2-shift of the alkyl group on copper with retention of configuration (Scheme 31). R'C=CCR2R30H -I* R'CrCCR2R30S(0)Me RR'C=C=CR2R3 Reagents i MeSOCl; ii (RCuBr)MgX-LiBr-THF R3 R' R3 (RCuBrj-\ \ R' CzC -C' / ' 1 'R2 R R2 0s(0)Me R-CU Scheme 31 A procedure which is similar in principle to the one shown in Scheme 31 uses the substituted pyridinoxy group as the leaving group.The 2-propargyloxypyridinium salt formed in situ from propargyl alcohols reacts with Grignard reagents in the presence of catalytic amounts of copper(1) iodide to produce the allene in high yield (Scheme 32).74 R'CfCCHOHR2 A [R1CGCCHR20py] 2R'R3C=C=CHR2 Reagents i pyF-NEt,; ii R'MgBr-CuI. py = Me Scheme 32 72 G. W. Kabalka R. J. Newton J. H. Chandler and D. T. C. Yang J.C.S. Chem. Cbmm. 1978,726. 73 P. Vermeer H. Westmijze H. Kleijn and L. A. van Dijck Rec. Truu. chim. 1978,97 56. 74 T. Mukaiyama and K. Kawata Chem. Letters 1978 785.