7. ALIPHATIC COMPOUNDS By M. F. Ansell (Chemistry Department Queen Mary College Mile End Road London E. 1.) Acetylenes.-Although the intramolecular additions of carbonium ions and free radicals to alkenes are clearly established reactions reports of cycli- sations involving acetylenic bonds are scarce. When' 6-bromo-1 ;phenylhex-1 -ene (1) reacts with an exceess of n-butyl-lithium at room temperature cyclisa- tion occurs probably by a radical mechanism to give the cycloalkene (2) the alternative product 1-phenylcyclohexene not being formed. Another but rather different intramolecular radical-reaction occurs in the peroxide-initiated addition of carbon tetrachloride to terminal alkynes (3) containing a chain of at least six carbon atoms. Beside the expected addition product (5) derivatives R[CHJ4CmCH R[CH,] 4&CH-C C13 R[CH,],CCl =CH-CCl3 / Me2C*C =CH I H (9) (1 0) H.R. Ward J. Amer. Chem. SOC.,1967,89,5517. 244 M.F. Ansell of 2,2-dichlorovinylcyclopentane(8) are formed.2u The latter are considered to arise by rearrangement of the intermediate vinyl-radical by a 1,5-hydrogen shift (4) + (6) followed by internal cyclisation (6) -+ (7) and elimination of a chlorine atom. Similarly radical addition of carbon tetrachloride to propargyl esters gives riseZb to y-lactones uia a 1,5-hydrogen shift from C* in structure (9). If the ester (9)is optically active due to asymmetry at C* then the y-lactone (10) produced retains the optical activity. The authors consider this is due to rapid trapping of the intermediate radical rather than the reaction being concerted.Trifluoroacetolysis of the m-nitrobenzenesulphonates of the 3-yn-1-01s (1 1) gives rise3 to derivatives of cyclobutanone (12) and alkylcyclopropyl ketones (13) the latter predominating in the presence of mercuric acetate. Although an ionic mechanism is involved the exact steps are not certain and two alternative routes are illustrated below for the cyclobutanone formation. By contrast with the olefinic compounds thermal rearrangement of acetylenic compounds have been little studied. It is now reported4 that 1,5-alkadiynes undergo intramolecular rearrangement at 300-400" to yield dimethylene- cyclobutenes e.g. (14) -,(15) and alken-5-ynes (16) undergo' reversible re- arrangement to 1,2,5-alkatrienes (17) which then undergo cyclisation to 3- and 0 6) (1 7) (18) (19) E.I. Heiba and R. M. Dessau J. Am. Chem. SOC.,1967,89 (a)p. 3772; (b)p. 2238. M. Hanack I. Herterich and V. Vott Tetrahedron Letters 1967 3871. W. D. Huntsman and H. J. Wristers J. Amer. Chem. SOC.,1967,89,342. W. D. Hunstman J. A. DeBoer M. H. Woosley J. Amer. Chem. Soc. 1966,88,5846. Aliphatic Compounds 4-methylenecyclopentenes (18) and (19). The thermal cyclisation of some acetylenic ketones is reported under oxygen compounds. The versatility of acetylenic compounds in organic syntheses is extended by the discovery that terminal ethynyl groups may be protected by trimethyl- silylation. Thus Grignard reagents of the type (20)may be prepared6 and also the preferential reduction (21) -,(22),of an internal triple bond in the presence of a terminal triple bond may be a~hieved.~ Desilylation is readily effected with silver nitrate solution to give the silver acetylide which with potassium Me,S i -C= C oMgBr.(a) EtMgBr then Me,SiCl (b) H,-Lindlar catalyst cyanide solution gives the free acetylene. The bis-( 1,l -diisobutylalanyl)alkanes (23) are readily available uia hydroalumination of 1-alkynes. They react with an alkyl-lithium or sodium methoxide in tetrahydrofuran to give the inter- mediates (24) which react' as shown in Scheme 1. All these reactions proceed in good yield (>70%) and appear to be general thus further enhancing the versatility of acetylenes in organic syntheses.Vinylalanes are readily available by the addition of di-isobutyl aluminium hydride to alkynes. This involves cis-addition to the triple bond yielding trans-vinylalanes from 1-alkynes and cis-vinylalanes from disubstituted alkynes. Treatment of such vinylalanes with methyl-lithium followed by carbonation yields the stereochemically pure trans-clp-unsaturated acid like- wise with aldehydes trans-allylic alcohols are f~rmed.~" Remarkably what is essentially a change in the order of addition of the two reagents namely by adding di-isobutylmethylaluminium hydride (from methyl-lithium and di- isobutylaluminium hydride) to disubstituted acetylenes resultsgb in trans-C. Eaborn A. R.Thompson and D. R. M. Walton J. Chem. SOC.(C),1967,1364. ' H. M. Schmidt and J.F. Arens Rec. Trau. Chim. 1967,86,1138. G. Zweifel and R.B. Steele Tetrahedron Letters 1966,6021. G. Zweifel and R.B. Steele J. Amer. Chem. SOC. 1967,89 (a) p. 2754; (b)p. 5085. 246 M. F. Ansell addition of the aluminium hydrogen bond to the triple bond and the resulting vinylalanates react with Grignard co-reagents to give pure cis-clfbunsaturated compounds. These reactions are illustrated by the conversion of the alkyne (25) to the acids (26) and (27). [;;c=c\Et AIBU * J LiC H\ Et/'= /COzH'\Et Et C= C Et (25) .Y Y (2 6) ' H\ 0Etc=c AlBu' Et/ \COzH (2 7) (a) AIHBui then MeLi; (b) Li[BuiCH,AlH] ;(c)C02 Synthetic routes to acetylenes containing hetero-rings have been reported. Thienyl and fury1 compounds may be synthesised by coupling a cuprous acetylide with an iodo-heterocycle in boiling pyridine" e.g.(28) + (29). This I CH,*C:C-Cu Cu.CiC.C02Me-I [LJ LrAI -CH,-C iC (2 8) CH,*C i C rnCiC.C02Me simple reaction takes advantage of the specific formation of cuprous acetylides and enables volatile acetylenic compounds to be used. It can be adapted" to the preparation of terminal acetylenes by use of a substituted acetylide having a readily removable substituent e.g. (30) -+ (31). Alternative approachesI2 consist in the condensation of propargylic aldehydes (32) with mercapto- ketones (33) in the presence of base to yield acyl-thiophens (34)and the reaction CuCi C .CH(OEt) ArCi C * Ad (30)ACu*Ci C- C0,Et lo F. Bohlman P.-H. Bonnett H. Hofmeister Chem. Bm.1967,100 1200; R E. Atkinson R F. Curtis and J. A. Taylor J. Chem. SOC.(C) 1967 578; R. E. Atkinson R F. Curtis and G. T. Philips ibid. p. 201 1. R. E. Atkinson R. F. Curtis D. M. Jones and J. A. Taylor Chem. Comm. 1967 718. l2 F. Bohlmann and E. Bresinksky Chem. Ber. 1967,100 107. Aliphatic Compounds 247 of polyacetylenes (35)with sodium sulphide to yield the thiophens (36)or with sodium bisulphide to yield the thiophen (36)and the dithiole (37). Acetylenic carotenoids have been reported for the first time (see below). -+ (32)Rl.CiCHO R'C4 CH-CH,'0 + R' aC0.R2 (34) (33)m.CH2.(-".R2 'S-cH2'c0RZ CH3 (36) CH [Ct CI2.C :C*CH* C-CH3 -CH,. [C iC] ,CHoCH3 (3 7) HS*S' s-s Carotatoxin a natural toxicant from the common carrot13 has been shown to be falcarinol (38).14 AUenes and Cumulenes.-A number of preparations of allenes have been reported which are variants of the reaction of a Grignard reagent with a propargyl halide.Thus 3-chloro-3-methylpent-2-yne with methylmagnesium CH3 :C CR .CHzX (39) halide yieldsI5 tetramethylallene free from all isomers ; allenic alcohols (39; X = OH) (80-90% purity the remainder being the acetylenic alcohol) are obtained16 by low-temperature inverse-addition of Grignard' reagents to 4-chlorobut-2-yn-l-ols and allenic bromides (39; X = Br) are the major product from Grignard reagents and 1,4-dibromobut-2-ynes.' Such reactions are considered18 to be S,2' reactions and not carbene reactions as previously suggested. l3 D. G. Crosby and N.Aharonson Tetrahedron 1967,23,465. l4 R. K. Bentley and V. Thaller Chem. Comm. 1967,439. J.-P. Bianchini and A. Guillemonat Compt. rend. 1967,264 C 600. l6 S.Gelin R. Gelin and M. Albrand Compt. rend. 1967,264 C 1183. N. Lumbroso-Bader E. Michet and C. Troyanowsky Bull. SOC.chim. France 1967 189. L. Brandsma and J. F. Arens Rec. Trav. chim. 1967,86,734. l9 F. Cerratosa. Tetrahedron L-etters 1964,895. 248 M.F. Ansell An unusual rearrangement” is the conversion of prop-2-ynyl toluene-p- sulphinate (40) in boiling chlorobenzene to propadienyl-p-tolylsulphone(41). A cyclic transition state may be involved. Cycloelimination leading to tetramethylallene (44)in good yield can be achieved2 by oxidation of 4-0~0-3,3,5,5-tetramethyl pyrazoline hydrazone (42) or by pyrolysis of the sodium salt of the toluene-p-sulphonylhydrazone (43).These are the first examples of this type of cycloelimination reaction. 92 02 (4 4) (43) Tetramethoxyallene (46) prepared” from tetramethoxyethylene (45) is the acetal of carbon suboxide. In contrast to other allenes due to the effect of the four methoxy-groups it is protonated on the central carbon atom as is shown by its conversion into dimethyl malonate by anhydrous hydrogen chloride. As a double keten acetal it is hydrolysed to dimethyl malonate and will add methanol to yield hexamethyl orthomalonate (47). (Me0)2C C(OMe) ‘f * CCl ( (45) (MeO),C CH C(OMe) CH,(CO,Me) (47) Photocatalysed di-addition of sulphur compounds such as aliphatic and aromatic thiols to allenes is a better route to trimethylene bis-sulphides than the replacement reaction of 1,3-dihalopropane~.~~ Addition of sodium thio- lates to allene24 gives in all cases more than 90% of the 2-propenyl sulphide RS-C(Me):CH,.It is probable that the reaction proceeds via propyne for with tetramethylacetylene no addition products were detected. The authors question whether any truly anionic additigns to allene have ever been effected. Cycloaddition of diazopropane to allenic esters2’ of the type (48; R = Me) when at least one of the groups R’ and R2is hydrogen give adducts of the type (49) in which as is expected electronically the nucleophilic diazocarbon atom becomes bonded to the carbon atom kto the carbonyl group. In contrast with yy-disubstituted allenes (48; R’ = R2= Me; R3 = H or Me) *’ C.J. M. Stirling Chem. Comm.,1967 131. 21 R.Kalish and W. H. Pirkle J. Amm. Chem. SOC. 1967,89,2781. 22 R.W.Hoffmann and U. Bressel Angew. Chem. 1967,79,823. 23 A. A. Oswald K. Griesbaum D. N. Hall and W. Naegele Canad. J. Chem. 1967,45 1173. ’* W.H.Mueller and K. Griesbaum J. Org. Chem. 1967,32,856. ’’ S. D.Andrews and A. C. Day Chem. Comm. 1967 902. Aliphatic Compounds (51) CH,[CH,] 16*CH:C CHCCH,] ,.C02H diazopropane adds to the @-double bond in the opposite sense to yield the isomeric 3-alkylidenepyrazolines (50). This is due to the severe overcrowding of alkyl groups see (49a) which must occur in the transition state leading to adduct of type (49) when R' = R2 = Me.Naturally occuring allenes continue to be reported and include the acid (51)26 and the carotenoid (75; X = f Y = g).27 1,2,3-Trienes can be obtained in excellent yield (7G-80% for buta-1,2,3- triene; 55 % for higher homologues) from 1,4-dichloro-2-alkynes by the action >CCl*CiC-CH,Cl L>C.C:C-CH, n. ->C:C:C:CH + [,Cl I; LlI-nI '1 I-c1-+ of zinc dust or sodium iodide (3 mole) in dimethyl sulphoxide.28 A possible mechanism is outlined in Scheme 2. These cumulenes are stable below -50° but liquefied butatriene may explode when warmed to 0".The authors state 'The cumulenes possess a very peculiar odour. After one has smelled a cumulene the smoking of cigarettes and cigars is unpleasant for at least two days'. n EtO. CH *O-mC i C -CH.0Me -R'R'C C CH -0Me I rn Me H B-(52 (53) Cumulenyl ethers (53) are prepared in good yield and reasonably pure (>90%) by addition of sodamide in liquid ammonia to the bis-ethers (52) in liquid ammonia. These ethers (53)are stable for an hour at 100-120" in an inert atmosphere but readily polymerise in the presence of oxygen.29 Progress in the chemistry of allenes has been re~iewed.~' Olefinc Compounds.-This year has seen the introduction of a number of 26 F. Bohlmann K. M. Rode and M. Grenz Chem. Ber. 1967,100,3201. 27 A. K. Mallams E. S. Waight B. C. L. Weedon L. Chohoky K. Gyorgyfy J. Szabolcs N. I. Krinsky B. P. Schimmer C. 0. Chichester T. Katayama L. Lowry and H. Yokoyama Chem. Comm. 1967,484. 28 P. P. Montijn L. Brandsma and J.F. Arens Rec. Trau. chim.,1967.86 129. 29 P. P. Montijn J. H. Van Boom,L. Brandsma and J. F. Arens Rec. Trau. chim. 1967,86 115. 30 K. Griesbaum Angew. Chem. 1966,78,953. 250 M.F. Ansell new routes to olefinic compounds. Some of them are considered later in this section under halides others under general methods. a-Lithiophosphonic acid bisamides [54; X = PO(NR,),] react with carbonyl compounds to give after protonation P-hydroxy-compounds [55 ;X = PO(NR,),] which in refluxing benzene or toluene in the presence of R3R4CLiX ('1 R'R2C=0 R1 RZC*CR 3R4X. R'RZC:CR3R4 A (2)H,O I -H OH (54) (55) (56) OLi (57) silica gel undergo an elimination reaction to give the olefin (56) in high yield. The reaction is generally more straightforward and the reagents cheaper than in the Wittig reaction.The elimination step is stereospecific and if the di- astereoisomeric intermediates can be separated then pure cis-and trans-olefins can be ~btained.~' Alkenes are also formed from 00'-dialkyl methyl- phosphon~thioates~~ as and s~lphinimides~~ illustrated by the reaction sequences (54) -,(56) X = PS(OR), and (57) -,(58) respectively. Alkynes have always been useful precursors'of alkenes and a new and convenient stereoselective syntheses of alkenes via the hydroboration-iodination of alkynes has been reported.34 Dialkylboranes (59) which are readily available from most cyclic and many acyclic alkenes readily add to alkynes to yield vinylboranes (60). On addition of iodine to the latter one alkyl group migrates from boron to carbon and subsequent hydrolytic removal of the boron gives the pure ( >99 %) cis-alkene (61)in high (63-85 %) yield.MezCH- CMe :N.NHTs MezCH.CH:CHz Sulphonylhydrazones having an a-hydrogen atom readily prepared from the corresponding carbonyl compounds react with butyl-lithium to yield alkenes which in many cases would otherwise be difficultly accessible. Thus 31 E. J. Corey and G. T. Kwiatowski J. Amer. Chem. SOC.,1966,88,5652,5653. 32 E. J. Corey and G. T. Kwiatkowski J. Am. Chem. SOC.,1966,88,5654. 33 E. J. Corey and T. Durst J. Amer. Chem. SOC.,1966,88,5656. 3* G. Zweifel H. Arzoumanian and C. C. Whitney J. Amer. Chem. SOC.,1967,89,3652. Aliphatic Compounds 251 the hydrazone (62) yields the terminal-alkene (63) probably via a carbanion me~hanism.~' Among the most characteristic reactions of alkenes is the addition of halo- gens.The addition of the pseudohalogens iodine m~noazide,~~ and NN-dichl~rourethane~(64) has now been reported. The former prepared in situ by the action of iodine monochloride on sodium azide in acetonitrile adds C12N- C0,Et +R CH:CHz -RCHCI- CH,. NH.CO,Et // NH 0-NH stereospecifically trans and with terminal alkenes the azido-function is at the 2-position. NN-Dichlorourethane is reasonably stable adding to terminal alkenes to yield P-chlorocarbamates (65) which with alcoholic potassium hydroxide yield aziridines (66) and on pyrolysis or in reflwing acetic acid give 5-substituted oxazolidones. (67). The novel 1,6-cycloaddition of sulphur dioxide to cis-hexa-1,3,5-triene yields3*2,7-dihydrothiepin-l,1 -dioxide (68).The hydroboration-oxidation of alkenes provides a highly convenient procedure for the anti-Markownikoff hydration of carbon-carbon double bonds3' A convenient indirect Markownikoff-hydration of the carbon- carbon bond by oxy-mercuration followed by in situ demercuration with Me C CH :CH Hg(oAT)-%NaBH4 Me3C-C H(0H) CH sodium borohydride is now rep~rted.~' That this reaction does not cause rearrangement is shown by the formation of 3,3-dimethylbutan-2-01 (70) from 3,3-dimethylbut-2-ene (69) in 94 %yield. A number of useful transformations of alkenes can be effected via trialkyl-borons following the discovery that the latter react with carbon monoxide.Thus trialkylborons in diglyme solution react readily with carbon monoxide at atmospheric pressure at 100-125" and subsequent oxidation of the reaction mixture with alkaline hydrogen peroxide yields a trialkyl~arbinol.~~" The reaction clearly involves migration of the .alkyl groups from boron to carbon. 35 R. H. Shapiro and M. J. Heath J. Amer. Chem. SOC.,1967,89 5735; G. Kaufman F. Cook H. Schecter J. Bayless and L. Friedman ibid. p. 5736. 36 F. W. Fowler A. Hassner and L. A. Levy J. Amer. Chem. SOC.,1967 89,2077. 37 T.A. Folgia and D. Swern J. Org. Chem. 1966 31 3625; 1967,32 75. W. L. Mock J. Amer. Chem. SOC.,1967,89 1281. 39 G. Zweifel and H. C. Brown Org. Reactions 1963,13 1. 40 H. C. Brown and P. Geoghegan J. Amer. Chem. SOC.,1967,89,1522.41 H. C. Brown and M. W. Rathke J. Amer. Chem. SOC.,1967,89 (a) 2737; (b)2738; (c) 2740. 252 M. F.Ansell Addition of a small quantity of water to the reaction mixture inhibits migration of the third alkyl group and thus subsequent oxidation of the organoborane intermediate yields a dialkyl ketone.41 If the initial reaction with carbon monoxide is carried out in the presence of sodium or lithium borohydride the reaction temperature may be reduced to 45" and the reaction controlled to achieve the transfer of only one group from boron to carbon; subsequent hydrolysis yields the homologated alcohol.41' Thus carbonylation of organo-boranes can be controlled to achieve migration of one two or three groups. All these reactions are summarised in Scheme 3.These reactions can be H,O,-NaOH -R3C*OH RB(0H)-CR,(OH) Hzoz-NaoH -.R,CO C0/45"/NaBH4 NaOH RCH,OH SCHEME3 adapted42 to prepare unsymmetrical ketones by the use of 'thexylborane' (2-butyl-2,3-dimethylborane) the alkyl group of which will not migrate from boron to carbon. This is shown in Scheme 4. By using this method ethyl Me,C:CMe + BH3 + Me,CH.CMe,*BH 4kene-% Me,CH-CMe,.BR,H 4sMe,CH.CMe,BR,R -2+ CO-H 0 Me,CH.CMe,.B(OH).CRARB(OH) Hzoz + RARBCO NaOAc SCHEME 4 7-methyl-5-0x0-octanoate (98 % pure) was prepared from isobutene and ethyl but-3-enoate in 84% yield. Conversion of an alkene RCH:CH into the corresponding acid RCH .CH .CO,H is achieved43 by formation of a cyclohexyl ketone using dicyclohexyldiborane followed by Baeyer-Villiger oxidation which occurs with preferential migration of the cyclohexyl group to form the corresponding cyclohexyl carboxylate.This is illustrated in Scheme 5. When an internal alkene is exposed to a catalyst composed of tungsten (C6HI1),BH + CH,:CH[CH,],.CH c!NaOAc C6H,,.CO-[CH,],.CH 1% CH3. [CH,],.C02H (a) Baeyer-Villiger oxidation SCHEME 5 42 H. C. Brown and E. Negishi J. Amer. Chem. SOC.,1967,89,5285. 43 H. C. Brown G. W. Kabalka and M. W. Rathke J. Amer. Chem. SOC.,1967,89,4530. Aliphatic Compounds 253 hexachloride ethanol and ethyl aluminium chloride the following novel metathesis takes place 2 R'CH :CHR @ R'CH :CHR' +R2CH:CHR2 The statistical proportion (2 1:1) of products is obtained the reaction is reversible and clean and deuteriation studies suggest that it proceeds via trans-alkylidenation rather than by trans-alkylati~n.~~ Dehydrogenation of several alk-1 -enes by lithium dispersions under mild conditions (20-120") to give the corresponding alk-1-ynyl lithium and lithium hydride has been rep~rted.~' The yield varies markedly with the chain length of the alkene reaching a maximum of 60 %with hex-1-ene.The reaction only applies to alk-1-enes. Photochemistry of alkenes is reviewed on p. 164 but attention is drawn to the photochemical dimerisation of tetramethylethylene to hexamethylcyclo- butane.46 This is one of the few examples of the photochemical dimerisation of a nonconjugated alkene. trans-Penta-1,3-diene (71) forms an inclusion compound with perhydro- triphenylene.If optically active (-)-(R)-perhydrotriphenylene is used and the inclusion compound subjected to y-irradiation the isotactic trans-1,5-poly- pentadiene (72) produced is optically active [CZ]:~~ = +9.8. The use of (+)-(S)-perhyrdotriphenylene leads to a polymer with the opposite sign of rotation. This novel example of an asymmetric synthesis shows that optical activity may be induced in simple chemical systems under rather primitive conditions in the absence of complex reagents or catalysts and by means of non-selective ionising radiati~n.~' Natural Products.-Squalene-2,3-epoxide a key compound in the biological conversion of squalene into cholesterol (see p. 524) has been found4* in cultivated tobacco tissues in uitro.Another important alka-polyene epoxide is the compound (73) which is the juvenile hormone (i.e. one of the factors C0,Me 0 44 N. Calderon Hung Yu Chen and K. W. Scott Tetrahedron Letters 1967,3327. 45 D. L. Skinner D. J. Peterson and T. J. Logan,J. Org. Chem. 1967,32 105. 46 D. R. Arnold and V. Y. Abraitys Chem. Cornrn. 1967 1053. 47 M. Farina G. Audisio G. Natta J. Amer. Chern. SOC. 1967,78 5071. 48 P. Benveniste and R. A. Massy-Westropp Tetrahedron Letters 1967 3553. 254 M.F. Ansell necessary for the post-embryonic development) of the giant silkworm moth. Its structure has been established by degradative and synthetic studies.49 The plant growth inhibitor dormin (74) shows similarities in structure to certain carotenoids and it has been shown5' that irradiated mixed carotenoids from dried nettles inhibited the growth of cress seeds as did (+)-dormin.Y (7 6) H H 49 K. H. Dahm B. M. Trost H. Roller J. Amer. Chem. SOC. 1967 89 5293; H. Roller K. H. Dahm C. C. Sweely and B. M. Trost Angew. Chem. 1967 79,190. H. F. Taylor and T. A. Smith Nature 1967 215 1513. Aliphatic Compounds A natural acetylenic sesquiterpene has been described,” as have three52 C,,-acetylenes which can be regarded as degraded sesquiterpenes. This year acetylenic carotenoids alloxanthin (75; X = Y = a)53identical with pectin- oxanthin and cynthiaxanthin,’ monoadoxanthin (75; X = a Y = c),~~ crocoxanthin (75; X = a Y = d),53 diatoxanthin (75; X = a Y = b),53 and pectenolone (75; X = a Y = e)54 have been discovered.Neoxanthin is identical27 with the allenic carotenoid folioxanthin (75 ;X = f Y = g). The carotenoids phlei-xanthophyll (76; X = H2) and (76; X = 0),isolated from mycobacterium phlei are the first reporteds5 natural tertiary D-glucosides. The first C,,-carotenoid encounted in nature isolateds6 from the non- photosynthetic bacteria Flavobacteriurn dehydrogenans has been provisionally called P439 and it is suggesteds7 that it has the structure (75; X = Y = h). Alkanes.-The gas-phase catalytic deuteriation of low molecular weight paraffins is known and it has now been shown’’ that high molecular weight hydrocarbons may be fully deuteriated in the liquid phase by passing deuterium gas through an exchange cell containing the hydrocarbon and a fixed-bed catalyst such as ruthenium palladium platinium or Raney nickel.Thus n-hexadecane is 99.4%deuteriated in 316 hr. at 190”. The ionisation of isobutane (77) -,(78) occurs in hydrogen fluoride-antimony pentafluoride solution. The reverse reaction which can be achieved” +-+-MeJCH+ HQ =Me3C++ H Me,C + H SbF -Me,C SbF + MeH (7 7) (78) (79) (80) in a two-phase solvent system (HF-Freon 113) amounts to electrophilic substitution at hydrogen. When6’ neopentane is dissolved in HF-SbF nucleophilic substitution at carbon by a proton takes place (79) + (80) and methane is evolved. The reverse reaction has not been observed. Carboxylic Acids and Related Compounds.-With very few exceptions a-metalation of aliphatic carboxylic acids has not been reported.Acetic acid with sodamide yields6 disodium acetate but homologous metalated acids are decomposed under the reaction conditions. However metalation with lithium di-isopropylamide in tetrahydrofuran or hexane appears to be a ’’ R. A. Massy-Westrop G. D. Reynolds and T. M. Spotswood Tetrahedron Letters 1966 1939 (cf. Annual Reports 1966). ’’ T. Nozoe Y. S. Cheng and T. Toda Tetrahedron Letters 1966,3663. ” A. K. Mallams E. S. Waight B. C. L. Weedon D. J. Chapman F. T. Haxo T. W. Goodwin and D. M. Thomas €hem. Comm. 1967,301. ” S. A. Campbell A. K. Mallams E. S. Waight B. C. L. Weedon M. Barbier E. Lederer and A. Salaque Chem. Comm. 1967,941. ” S. Hertzberg and S. L. Jensen Acta Chem. Scand. 1967 21 15. S. Liaanen Jensen and 0.B.Weeks Norweg. J. Chem. Mining Met. 1966,26 130. ” S. Liaanen Jensen Acta Chem. Scand. 1967,21 1972 ” J. G. Atkinson M. 0.Luke and R. S. Stuart Canad. J. Chem. 1967,445 1511. ’’ A. F. Bickel C. J. Gaasbeek H. Hogeveen J. M. Oelderik and J. C. Platteeuw Chem. Comm. 1967,634. 6o H. Hogeveen and A. F. Bickel Chem. Comm. 1967,635. 61 D. 0.DePree and R. D. Closson J. Amer. Chem. SOC.,1958,80,2311. 256 M.F. Ansell general reaction for aliphatic alkenoic and araliphatic acids.6Z This is illus- trated by the formation of lithiated-isobutyric acid (82) which is stable in the solvent system up to 40".These reagents can be alkylated with alkyl halides and with epoxides (81) (e.g. a 17,20-epoxy-steroid) yield spiro-lactones such as (83). The chlorination of the esters CH,[CH,];CO,Me where n = 2,3,4 or 5 by N-dichlorodimethylamine in an acidic medium is highly ~elective.~ In each case more than 70% of the monochlorinated material has the chlorine attached to the carbon atom adjacent to the terminal methyl group.Chlori- nated esters may also be prepared from hydroxy-esters under almost neutral conditions by heating them with triphenylphosphine and carbon tetra-chloride.64 The reaction proceeds with inversion at !he reaction centre and a possible reaction route is shown in Scheme 6. Esters of dichloroacetic acid RCH(OH)*CO,R' + [Ph,P*CCl,]+Cl-+ [Ph3P.0*CHR-C02R']+ C1- + CHC1 1 RCHCl*CO,R f Ph,PO SCHEME 6 can65 be used as the 'reactive methylene component' in the Michael reaction as shown by the formation of the ester (84) from methyl a-methylmethacrylate and ethyl dichloracetate.A disadvantage of the direct acylation of sodio-malonic esters as a route to acyl-malonic esters is that the primary product is often further acylated. This /OEt Me02C. CCl,. CH,-CHMe-CO,Me EtO,C.CH :C RCO .CH(CO,Et) \ OSiMe (84) (85) (86) 62 P. L. Creger J. Amer. Chem. SOC. 1967,89,2500. 63 F. Minisci R. Galli A. Galli R. Bernardi Tetrahedron Letters 1967 2207. 64 J. B. Lee and I. M. Downie Tetrahedron 1967,23,359. " H. Timmler and R. Wegler Chem. Ber. 1967 100,2362. Aliphatic Compounds may be overcome66 by reaction of the sodio-malonate with trimethylsilyl chloride to yield the ‘keten acetyl’ (85) which will react readily with an acyl halide RCOCl eliminating trimethylsilyl chloride to give the acylmalonic ester (86).The oxidative decarboxylation of disubstituted malonic acids (87) + (88) provides a useful route to ketones and is achieved67 in two stages by reaction with lead tetraacetate The ketones are obtained in yields of 45-70 % which is very satisfactory in view of the simplicity of the process. The existence of two forms of succinyl dichloride (89) and (90)has in the past been assumed6* in order to explain the formation of abnormal products such as (92) from its reaction with triethylaluminium trichloride. However there is no physical evidence to support the existence of the cyclic form and n.m.r. evidence shows that it exists predominantly in the acyclic form.The formation of the product (92) cap be explained on the basis of a [3,2,1]-bicyclic mecha- ni~m~~as illustrated (91) - (92). CH,. COCl . I CH,. CO C1 (89) Ci Et OAl R,I Cl Et CH * I CH,. COzH CH. Et C1I (90) Friedel-Craft reactions are usually associated with aromatic compounds however the single-step condensation of succinyl chloride with carboxylic acids RCH C02H under Friedel-Craft conditions yields” 2-alkylcyclo-pentan-1,3-diones (93; n = 1). These compounds are important in steroid syntheses and can also be obtained7’ by the cyclisation of y-0x0-carboxylic acids RCH CO. [CH,] C02H with aluminium chloride in the presence of an acylating agent such as acetyl or propionyl chloride. The use of glutaryl chlorides or 6-0x0-acids leads to the 2-alkylcyclohexane-l,3-diones (93; n r= 2).CH,.CO \ /O\ CHR CH,[CH,],.CH. CH -CH,*CH=CH[CHz],.CO2Me (94) [AH,]n.CO/ (93) (95) 66 U. Schmidt and M. Schwochau Tetrahedron Letters 1967,4191. 6’ J. Tufariello and W. J. Kissel Tetrahedron Letters 1966 6145. 68 G. H. Schmid Canad. J. Chem. 1966,44,2917. 69 M. S. Newman and C. Courduvelis J. Amer. Chem. SOC.,1964,86,2942. ’O H. Schick G. Lehmann and G. Hilgetag Angew. Chem. 1967,79,97. ’’ H. Schick G. Lehmann and G. Hilgetag Chem. Ber. 1967,100,2973. 258 M.F. Ansell The unusual rearrangement of methyl vernolate (94) in the presence of boron trifluoride etherate to the cyclopropane acid (95)has been reported.72 Nitrogen Derivatives.-In 1864 Guether7 reported correctly that triethyl- amine is converted to diethylnitrosamine by aqueous nitrous acid.Yet in 1967 a paper74 was still able to open as follows ‘The belief that tertiary aliphatic amines do not react with nitrous acid is one of the most persistent myths in organic chemistry . . . .’. In general an alkyl group is removed oxidatively and appears as an aldehyde or ketone and the nitrogenous portion is converted into a nitrosamine. The reaction is consider to proceed via hydrolysis of an immonium salt (Scheme 7). RiN-CHR; + HNO + R:k(CHRi)NO + R:I;I=CR;* + HNO HNO R:N=CR; + H2O + R;C:O + Ri6H2 -2 R:N*NO SCHEME 7 Condensation of secondary amines with ketones or aldehydes in the presence of stoicheiometric quantities of titanium tetra~hloride~~ gives rise to enamines in 55-94 % yield.(Scheme 8). The use of enaminesin the alkylation of ketones76 2R’CH,COR2 + 6R;”H + TiCl + 2R’.CH=CR2NR + 4RiNH,CI + TiOz SCHEME 8 is well established. Alkylation of enamines derived from aldehydes often leads to N-alkylation and aldol condensation. However aldehyde enamines derived from n-butylisobutylamine can often be alkylated in good yield77 (Scheme 9). C,H,. CH CHO -+ C,H,. CH=CH .NBu”Bu’ me&C,H,- CHMe -CHO SCHEME 9 Fulminic acid undergoes 1,3-dipolar cyclo-addition reactions.78 Thus with methyl acrylate methyl 2-isoxazoline-5-carboxylate(96) is formed. Such reactions are incompatible with the classical carboxine strwture C-NOH for fulminic acid but agree with the formonitrile structure (97). Thus sup- porting the recent79 i.r.spectroscopic evidence in favour of the latter structure. 72 H. B. S. Conacher and F. D. Gunstone Chem. Comm. 1967,984. 73 B. Guether Arch. Pharm. 1864 [2] 123,200. 74 P. A. S. Smith and R. N. Loeppky J. Amer. Chem. SOC. 1967,89 1147. ” W. A. White and H. Weingarten J. Org. Chem. 1967,32,213. 76 G. Stork A. Brizzolara H. Landesman J. Szmuskovicz and R. Terrell J. Amer. Chem. SOC. 1963,85 207. ” T. J. Curphey and J. C. Hung Chem. Comm. 1967,510. ” R. Huisgen and M. Christ Angew. Chem. Internat. Edn. 1967,6,456. 79 W. Beck and K. Feldl Angew. Chem. Internat. Edn. 1966,5,525. Aliphatic Compounds Monosubstituted alkyl di-imides have been postulated as reaction inter- mediates but have never been isolated. t-Butyldi-imide (98) produced by the base-catalysed decomposition of tetra-n-butyl (or tetramethy1)ammonium t-butylazoformate (99) has now been detected spectroscopically.80 Cyanogen azide N,CN which must be handled with extreme care as when it is neat it detonates violently adds to acetylene to form a 1:1-adduct,81 which is a tautomeric mixture of 1 -cyano-1,2,3-triazole (100)and a-diazo-N-cyanoethyl- - c [H-CEN-0 -H-C=N=O] (97) (98) Me3C-N:NH NC-N /N\ ‘N Ld NC -N idenimine (101).Similar results are obtained with methyl- and dimethyl- acetylene but the ethoxyacetylene adduct exists exclusively as the open-chain ethyl a-diazo-N-cyanoacetimidate (102). Cyanogen azide decomposes smoothly at ca. 40” to yield cyanonitrene :N .CN. The latter inserts stereospecifically into tertiary C-H bonds as is shown by its reaction with the 1,2-dimethyl- cyclohexanes.Each isomer yielding a single stereochemically pure cyanamide. [e.g. (103) -+ (104)]. The stereochemistry of the adduct (104) was not proved. Reversal of the assignment would mean that the reaction proceeded with inversion of configuration which the authors consider unlikely.82 (103) (1 04) +-[H,N-C-C=N ++H,N=C-C_N -H,~==c=c=N ++ P. C. Huang and E. M. Kosower J. Amer. Chem. SOC.,1967,89 391 1. M. E. Hermes and F. D. Marsh J. Amer. Chem. Soc. 1967 89,4760. ” A. G. Anastassiou and H. E. Simmons J. Amer. Chem. Soc. 1967,89 3177. I8 260 M. F. Ansell Considerable selectivity is shown by ethoxycarbonyl-nitrene from ethyl azidoformate when it undergoes insertion into C-H bonds to yield carba- mates (R-H + RNH -C0,Et).The reactivity of primary secondary tertiary C-H bonds in alkanes was found83 to be 1 10:32. With cyclic ethers,84 insertion of ethoxycarbonylnitrene occurs exclusively into the C-H bond adjacent to the oxygen atom. The carbamates (105) and (106) being the sole products from the parent ethers (105a) and (106a). Nitrenes and the decomposition of carbonylazides have been re~iewed.~ Base-catalysed polymerisation of hydrogen cyanide yields a mixture of products including a tetramer diaminomaleonitrile (1lo) a pentamer poly- meric amino-acid precursors and black intractable solids believed to have a fused-pyridine structure. Whatever the routes to these products the key intermediate is probably the dimer which in the absence of experimental evidence has been assumed to be iminoacetonitrile HN=CH * CN however it might be the isomeric iminocyanocarbene (107).Thermal or photolytic decomposition of the sodium salt of 1 -cyanoformamide toluene-p-sulphonyl- hydrazone (109) which would be expected to yield iminocyanocarbene yields86 the hydrogen cyanide tetramer diaminomaleonitrile (1 lo) as the major product. Iminocyanocarbene identified spectroscopically is formed as a yellow product on irradiation of the hydrazone (109) at -196". It exhibits no triplet state e.s.r. signals and therefore exists in the singlet state (108) with considerable dipolar character. Aminocarbene may be a key intermediate in hydrogen cyanide polymerisation and prebiological organic syntheses.Among the naturally occurring nitrogen compounds reported this year are fragin (1 11),87 isolated from Pseudornonasfragi a growth inhibitor which at a Me[CH,],.CONH.CH,-CH.CHMe HO,C.CH.CH,.N(OH).NO I I N(0H).N=O NH (1 11) (112) CH3[CH2] 12-CH(O&)-CH,. C0,[CH,],&Me3CI concentration of 20 p.p.m. inhibits the growth of Chlorella and Aspergillus niger. It contains the rare N-nitrosohydroxylamine group which is also found in the antibiotic alanosine (112),88 isolated from Streptomyces alansinicus D. S. Breslow T. J. Prosser A. F. Marcantonio and C. A. Genge J. Amer. Chem. Soc. 1967 89,2394. 84 H. Nozaki S. Fujita H. Takaya and R. Noyori Tetrahedron 1967,23,45. W. Lwowski Angew. Chem. Internat. Edn. 1967,6 897.86 R. E. Moser J. M. Fritsch T. L. Westman R. M. Kliss and C. N. Mathews J. Amer. Chem. SOC.,1967,89 5673. '' S. Tamura A. Murayama and K. Hata Agric. and Eiol. Chem. (Japan) 1967 31 758; S. Tamura A. Murayama and K. Kagel ibid. p. 996. G. C. Lancia A. Diene and E. Lazzari Tetrahedron Letters 1966 1769. Aliphatic Compounds 26 1 nsp. which has some antiviral and antitumour proper tie^.^^ Pahutoxin (113) is the poison of the blue boa fish which is toxic to fish of other species.g0 Sulphur Derivatives-Refluxing trifluoroacetic acids affords an excellent medium for the preparation of thioacetates and thioacetals. However in the absence of other carbonyl ethane thiol undergoes the un-precedented condensation with the acid giving the ortho-thiol ester (114).Esters of carboxylic acids can be C-alkylated with alkyl halides using sodamide in contrast alkylation of dithioesters RICH .CS. SR’ with R’Br occurs at sulphur to yield9’ ketone thioacetals (115). Thioketens apart from the perfluorinated compound (116)93 are very unstable.94 However some in situ reactions of thioketens have been reported. Acetylthioalkynes react as shown in Scheme 10 with diethylamine to yield probably viu a thioketen N-substituted thioamides and N-substituted acetamides. RCd-SCO-CH + Et,NH -+ [R-CS-SH] + CH3.CONEt2 RCH2.CS NEt2- Et,NH RCEI=C=S SCHEME 10 Crystalline methanesulphinic acid CH * SO.OH has been obtained9’ for the first time from its previously known acid chloride. All the molecules within a particular crystal have been shown by X-ray study to have the same chirality.That is they are all (S) or all (R). An attempt to convert a single optically active crystal of the substance into optically active methyl methane- sulphinate by the action of diazomethane failed. The first reported sulphinyl isocyanate CCl * SO-NCO is obtained96 by the action of silver cyanate on the corresponding sulphinyl chloride. Thermolysis go” of t-butylsulphoxide (117) eliminates isobutene to yieldg7 the first aliphatic sulphenic acid t-butylsulphenic acid (118). Its structure has 89 Y. K. S. Murthy J. E. Thieman C. Coronelli and P. Sensi Nature 1966 211 1198. ’O D. B. Boylan and P. J. Scheuer Science 1967,155,52. ” D. L. Coffen Chem. Comm. 1967. 1089. 92 P. J. W. Schuijl L.Brandsma and J. F. Arens Rec. Trav. chim. 1966,85,1263. ’3 M. S. Raasch Chem. Comm. 1966,577; see Ann Rep. 1966 p. 386. 94 H.E. Wijers C. H. D. Van Ginkel L. Brandsma and J. F. Arens Rec. Trao. chim. 1967,86,907. 95 F. Wudl D. A. Lightner and D. J. Cram,J. Amer. Chem. SOC. 1967,89,4099. 96 A. Senning Angew. Chem. 1966,78 1100. ’’ J. R. Shelton and K. E. Davis J. Amer. Chem. SOC. 1967,89,718. 262 M.F. Ansell been confirmed spectroscopically and from its reaction with electrophilic olefins such as ethyl acrylate with which it forms ethyl /3-(2-methylpropyl-2- sulphinyl) propionate (1 19). The N-sulphonylamines (121) are a new class of compounds and are obtained" by the action of triethylamine on sulphamoyl chlorides (120) in (Bu'),$-O Bu'S.OH But~.CHZ.CHZ.CO2Et I 0-RN=SO2 RNH .SOzCl EtNH -SOZ*NHPh Ph-C+& PhN--Ca L'N-&02 EtOI2 CO-Ph (123) (124) (125) toluene at -75". They cannot be isolated but addition of aniline to a cold toluene solution of (121 ; R = Et) yields N-phenyl-N'-ethylsulphamide(122). The analogous benzoyl derivative (124) is more electrophilic and reacts with ethyl vinyl ether to give the cycloadduct (123). If a toluene solution of the compound (124) is allowed to warm from -78" in the absence of a trapping agents exclusive formation of phenylisocyanate occurs. This reaction (124) (125) may involve the ol-elimination of sulphur dioxide. Oxidation of dialkyl disulphides with chloramine in the presence of ammonia in acetoni trile yieldsg9 the dialkyl sulphone di-imines which have been assigned structures (126)'' and (127).'0° The former structure (126) is now supported"' (126) (127) (128) by i.r.and Raman spectroscopy. These compounds are sufficiently stable to be gas chromatographed they are very soluble in water and are resistant to both acid- and base-catalysed hydrolysis. They react with halogens (CI Br and I) in aqueous solution buffered by potassium carbonate to yield NN'-dihalogeno-SS-dialkylsulphurdi-imines(128) which have the usual properties of N-halogeno-compounds. 98 G. M. Atkins jun. E. M. Burgess J. Amer. Chem. SOC.,1967,89,2502. 99 J. A. Cogliano and G. L. Brande J. Org.Chem. 1964,29,1397. loo R. H. Appel H. Fehlhaber D. Hanssgen and R. Schollhorn Chem. Ber. 1966,99 3108.R. G. Laughlin and W. Yellin J. Amer. Chem. SOC.,1967,89,2435. Io2 R.Appel and D. Hannsgen Angew. Chem. 1967,79,96. Aliphatic Compounds The highly reactive diphenylsulphonium isopropylylid (129) which can be obtained by the action of t-butyl-lithium on diphenylisopropylsulphonium fluoroborate in tetrahydrofuran at -70°,reacts with nonconjugated carbonyl compounds to yield'03" oxirans (130) but with ap-unsaturated carbonyl compounds addition occurs at the carbon-carbon double bond to yield"3b PhCHO Ph2S=C Me Me2C==CH-CH=CH -CO,Me Me2C=CH-CH-CH.C0,Me (1311 (129) MexMe + Me2 S -CH. C02R p-MeC6H,SO; Me 2S -CH2.C02Me (132) (133) gem-dimethylcyclopropanes (131). Dimethylsulphonium methoxycarbonyl-methylylid (132; R = Me) is a crystalline solid stable in an inert atmosphere at -20" for an extended period is obtained1O4 by the action of potassium t-butoxide on methyl dimethylsulphonium acetate toluene-p-sulphonate (1 33).The ethyl ester (132; R = Et) which is reasonably stable at -lo" is obtainedlo5 from the corresponding sulphonium bromide by the action of saturated potassium carbonate containing one equivalent of sodium hydroxide. Both these ylids react with ap-unsaturated carbonyl compounds to yield methoxy- carbonylcyclopropane derivatives. The polar lipids isolated to date generally consist of a long aliphatic chain of at least fourteen carbon atoms with a polar functional group at one end. 1,14-Docosyl disulphate has been isolated106 from the phytoflagellate Ochromonas danica and is the first polar lipid which has functional groups at both ends of the molecule and is the first known aliphatic sulphate lipid.Oxygen Derivatives-Trialkylborons Alk3B available via hydroboration of alkenes undergo a remarkably fast 1,4-addition to methyl vinyl ketone (134 ;R = Me) and acraldehyde (1 34 ;R = H) to yield the adducts (1 35) which CHSH-COR A1 k -CH,*CH-L R*OBAlk2 A1k .CH CH .COR (134) (135) (136) (137) (138) (1 39) lo3 (a)E. J. Corey M. Jautelat and W. Oppolzer Tetrahedron Letters 1967 2325; (b) E. J. Corey and M. Jautelat J. Amer. Chem. SOC. 1967,89 3913. lo4 J. Casanova and D. A. Rutolo Chem. Comm. 1967 1224. lo5 G. B. Payne 154th National Meeting Amer. Chem. SOC. Chicago Ill. Sept. 11-15th 1967 Organic Section Paper 158.lo6 G. L. Mayers and T. H. Haines Biochemistry 1967,6 1665. 264 M.F. Ansell on hydrolysis produce the corresponding carbonyl compounds (1 36). The complete generality of this reaction remains to be established as only the only carbonyl substrates used have been the two mentioned above.lo7 The reductive (Mg-CH3 * C02H) coupling of acetylacetone in hydrocarbon media yields as the main product the bis-acetal(l39) with the noradamantane skeleton. The reaction is considered to proceed via reductive coupling of the enol-form of acetylacetone (1 37) which cyclises to the bis-hemi-acetal (1 38) the latter on dehydration forms (139). In aqueous media in which acetyl- acetone exists in the diketone form no reductive dimerisation is observed.Io8 Dimerisation of aldoketens to their p-lactone dimers is catalysed by triethyl- amine.This catalyst is not effective in converting 0x0-ketens into p-lactone- dimers in fact dehydrohalogenation of isobutyryl chloride in the presence of triethylamine yields tetramethylcyclobutane-1,3-dione (143). It is now shown"' that the product from the triethyl phosphite-catalysed dimerisation of dimethyl- keten contains 94 % of the p-lactone dimer (142) and 3 % of the cyclobutane dione (143). A suggested mechanism for the reaction is shown in Scheme 11. /Me,C=C=O (140) I_ I 0- Me2(3=C-CMe2I I 0-C=O (142) (141) +/ €'(OR) 3 SCHEME 11 The effectiveness and selectivity of the catalyst depending on its ability to co- ordinate with the carbonyl-carbon and give the zwitterions (140) and (141).Base-catalysed (BuLi) disproportionation of the dimer (143) leads to the dimethylketen trimers (144) and (145).'" Alk-7-en-2-ones (146) on heating at 300-400" are cyclised in almost quanti- tative yield to alkylcyclopentyl ketones (148)' This reaction has been applied to many compounds having this skeleton and also to compounds which are precursors of alk-7-en-2-ones such as the derived enol-acetates ketols and 3-ethoxycarbonyl derivatives. The suggested mechanism of this reaction in- volving the intermediate enol(l47) is similar to that proposed112 for the cycli- lo' A. Suzuki A. Arase H. Matsumoto M. Itoh H. c.Brown M. M. RogiC and M.W. Rathke J. Amer. Chem. SOC. 1967,89 5708; H. C. Brown M. M. RogiC M. W.Rathke and G. W. Kabalka ibid. p. 5709. P. F. Casals and J. Wiemann Bull. SOC.chim. France 1967,3478. Io9 E.U.Elan J. Org. Chem. 1967,32,215. R. D. Clark J. Org. Chem. 1967,32 399. F. Rouessac P. LePerchec and J.-M. Conia Bull. SOC.chim. France 1967,818,822,826. W.D. Huntsman and T. H. Curry J. Amer. Chem. Soc. 1958,80,2252; W. D. Huntsman V. C. Soloman and D. Eros ibid. p. 5455. Aliphatic Compounds (146) (147) (148) (149) (150) (151) (152) (153) (157) (154) (155) sation of octa-1,6-diene and is consistent with the observed steric course of the reaction. Similar cyclisation reactions leading to five-membered rings have been reported. For example the A6-aldehyde (149) at 320" yields the aldehyde (150)' l3 and the alk-7-yne-2-one (151) at 260" yield the cyclopentenyl ketones (152) and (153).'14 These cyclisation reactions are not restricted to the formation of five-membered rings as non-8-en-2-one (154) at 360" yields (80 %) the cyclohexyl ketone (155) and dodec-11-en-2-one (156) at 390" yields (30%) the cyclodecyl ketone (1 57).' The modification of functional group properties by perfluorination can lead to novel reactions and compounds with unexpected properties.Hexafluoro- acetone reacts' with hexaphenylcarbodiphosphorane (158) in diglyme to form the cyclophosphorane (159) m.p. 155-157". This is the first stable 'Wittig intermediate' and on being heated in an inert solvent the Wittig reaction is completed to yield (160). 'I3 R. Bloch and J.-M. Conia Tetrahedron Letters 1967 3409.'I4 F. Rouessac P. LePerchec J. L. Bouk and J. M. Conia Bull. SOC. chim. France 1967,3554. 'I5 J.-M. Conia and F. Leyendecker Bull. SOC. chim. France 1967,830. '16 G. H. Birum and C. N. Mathews Chem. Comm. 1967 137. 266 M. F. Ansell The carbonyl group is normally resistant to attack by radicals. However in perfluoro-ketones the double bond more closely resembles the double bond in a weakly polarised olefin than it does the carbonyl group in a hydrocarbon ketone. This permits' ' the radical addition of a hydrocarbon to the carbonyl group (Scheme 12 R = cyclohexyl). R H +(C F3 )F=O R-orhv CF3C(OH)R+CF3CH* OR SCHEME 12 Metal fluorides catalyse the addition of fluorine to the carbonyl group in perfluoro-carbonyl compounds. In this way the fluoroxy-compound F,C- OF is obtained' l8 from perfluoroformaldehyde.Addition of fluorine to carbon dioxide"** '" gives CF,(OF) in almost quantitative yield. The latter is also obtained',' by fluorination sodium oxalate or sodium trifluoroacetate. It is a liquid b.p. -64",and has considerable thermal stability (unchanged after 6 hr. at 150")compared with other fluoroxy-compounds. It is strongly oxidising towards reducing agents such as mercury potassium iodide and aqueous alkali. The unstable and explosive bis-fluoroxy-compound FO-CF,*O-CF,*OF is obtainedI2' by addition of fluorine to the bis(fluorocarbony1)peroxide FCO -0.0 COF. The existence stability and isolation of alkyl-polyoxide has been dis- cussed,' 22 but the existence of such compounds has remained questionable.The reported'23 isolation of di-butyl peroxide was shown to be incorrect,'23* but the low temperature oxidation Df t-butyl- and cumyl-hydroperoxides apparently proceeds via the formation of tri0~ides.l~~ Evidence has now been (161) R 00.0* OR R10.0-OR2 (162) pre~ented'~' from an e.s.r. study of the irradiation products of di-t-butyl- peroxycarbonate that di-t-butyltetroxide (161) is stable below -70" and di-t- butyltrioxide (162; R' = R2 = But)is stable below -35". A further illustration of the effect of fluorine substitution on reactivity referred to above is the E. G. Howard P. B. Sargeant and C. G. Krespan J. Amer. Chem. SOC.,1967,89,1423. 'I8 M. Lustig A. R.Pitochelli and J. K. Ruff,J. Amer. Chem. SOC. 1967,89,2841.F.A.Hohorst and J. M. Shreeve J. Amer. Chem. SOC.,1967,89,1809. I2O P. G. Thompson J. Amer. Chem. SOC.,1967,89 1811. '" M.Lustig and J. K. Ruff Chem. Comm. 1967,870. '22 S. W.Benson J. Amer. Chem. SOC.,1964,863922. 12' Ann. Reports 1966,63 387. 12* P. D.Bartlett and P. Giinther J. Amer. Chem. SOC.,1966,88,3288. 12' P.D.Bartlett and G. Guaraldi J. Amer. Chem. SOC. 1967,89,4799. Aliphatic Compounds formation of bis(perfluoromethy1)trioxide (162; R' = R2 = CF,) in high yield (87%) by the reaction of one mole of oxygen fluoride with two moles of carbonyl fluoride.'26 This compound b.p. -16" is remarkably stable having a half-life of 65 weeks at 25". The trioxide (162; R' = R2 = CF,) is also formedI2' in low yield by fluorination of sodium trifluoroacetate together with the trioxide (162; R' = CF, R2 = CF,CF,) and possibly the tetroxide (161; R = CF,).Halogen Derivatives-The aliphatic halides are key compounds in organic syntheses and the past year has seen outstanding developments in this field particularly in the preparation and use of vinyl halides The conversion of alk-1-ynes to cis- and trans-vinyl bromides via hydro- boration has been reported'28 and is shown in Scheme 13. Alk-1-ynes react with bis-(3-methyl-2-butyl)boron (referred to as disiamylborane ;abbreviated to Sia,BH) to yield trans-alkenyldisiamylboranes. The latter react with c BSiaz A1k.C fCH (163) H\ c=c Br A1k0 H... I 'C-c-' -,c =c Ald \H Alk H L (164) SCHEME 13 bromine (presumably trans-addition) and the resulting dibromides will undergo elimination of the elements of disiamylboron bromide either solvolytically (trans) to yield the cis-vinyl halide or thermally (cis) (in boiling carbon tetra- chloride) to give the trans-vinyl halide.The cis-halides are obtained > 95% pure and the trans-halides > 88% pure. With phenylacetylene the stereo- chemical results obtained are reversed i.e. solvolysis gives the trans-isomer. Hydroboration of 1 -bromo- or 1-iodo-alkynes readily available by the low temperature halogenation of the corresponding lithium alkynes with dicyclo- hexylborane affords12' the trans-a-halovinylboranes (165) a new class of stable organoboranes which on protonolysis with acetic acid yield cis-vinyl halides (163) ( >85 % steric purity).The conversion of alk-1-ynes to trans-vinyl halides may be achieved',' by converting them into the corresponding vinylalanes (166) by the addition of L. R. Anderson and W. B. Fox,J. Amer. Chem. SOC.,1967,89,4313. I*' P. G. Thompson J. Amer. Chem. SOC.,1967,89,4316. H. C. Brown D. H. Bowman S. Misumi and M. K. Unni J. Amer. Chem. SOC.,1967,89,4531. G. Zweifel and H. Anoumanian J. Amer. Chem. SOC.,1967,89 5086. "O G. Zweifel and C. C. Whitney J. Amer. Chem. SOC.,1967,89,2753. 268 M.F. Ansell (165) (16 6) di-isobutylaluminium hydride followed by halogenation with iodine or bromine to give the trans-vinyl halide (164)(>98 % steric purity). The conversion of propargylic alcohols to vinyl halides has been a~hieved,'~' as is illustrated by the conversion of the alcohol (167) into the P-iodo-alcohol (168) by reduction with lithium aluminium hydride aluminium chloride followed by iodination (excess of iodine at -78").The replacement of aluminium chloride by sodium methoxide in the above reaction sequence lead specifically to the y-iodo-alcohol (170).No explanation has yet been advanced for this unprecedented positional selectivity. f RC-C*CH,OH -RpCH20H -& RpCH20H \ H H (167) (168) (16 9) H H The Wurtz-type of reaction of aliphatic halides has an attractive simplicity which is not always realised in practise. However this year has produced a number of novel improvements in the means of carrying out such reactions. The previously unreported dimerisation of vinyl halides can be achieved' 32 by the action of cuprous chloride on a tetrahydrofuran solution of a vinyl-magnesium halide at -40" to -60".A vinyl-copper@ complex is formed which on warming to + 20" gives the diene in good yield with separation of elemental copper.The symmetrical coupling of other alkyl halides may be achieved converting them via the derived organolithium or magnesium compound into the copper(1)ate complex by reaction with tetrakis [iodo-(tri-n-butylphosphine) copper(^)] which with molecular oxygen at low temperature undergoes oxidative coupling (Scheme 14).'33 This reaction resembles the oxidative- coupling of cuprous acetylides. The more difficult specific cross-coupling E. J. Corey J. A. Katzenellenbogen and G.H. Posner J. Amer. Chem. SOC. 1967,89,4245. 13' T. Kauffmann and W. Sahm Angew. Chem. 1967 79,101. "' G. M. Whitesides J. Sanfilippo jun. C. P. Casey and E. J. Panek J. Amer. Chem. SOC. 1967 89,5302. Aliphatic Compounds 02 C4H9Li+ [ICuP(C,H&] -0 C,H,CuLi -GH 18 -78" -78" SCHEME 14 reaction has been achieved'34 by the use of lithiumdialkylcopper of which the methyl isomer has been most studied. It is an ether-soluble complex prepared by the action of 1 mole equiv. of cuprous chloride on 2 mole equiv. of methyl- lithium. It reacts with a wide variety of organic halides (see organometallic section). An illustration' 31 of its reactivity is the stereospecific reaction with the halide (170) to yield trans-farnesol (171).The isomeric halide (168) yields the farnesol isomer (169). The overall reaction sequence (167) -N (169) or (174) is (172) (173) BrCH -CH=CH[CH2]n. CH=CH.CH,Br 1 (174) (175) PCH2 Br Y = [CH,],; n = 1 2,3 or 4 or CH,.O-CH applicable to a wide variety of synthetic problems in which stereospecific formation of a trisubstituted olefinic linkage is involved. Previously acetylenic precursors have been widely used for the stereospecific synthesis of cis-and trans-alkenes of the type XCH :CHY and certain trisubstituted alkenes from symmetrical acetylenes but they have not previously been used in the stereo- specific synthesis of more highly substituted olefins from unsymmetrical acetylenes. Cross couplings involving allylic halides can be achieved' 35 using n-allyl- nickel(1) bromides (172)which are readily obtained by the reaction of the allylic 134 E.J. Corey and G. H. Posner J. Amer. Chem. SOC.,1967,8!2,3911. 135 E. J. Corey and M. F. Semmelhack J. Am. Chem. SOC.,1967,89,2755. 270 M.F. Ansell bromide with an excess of nickelcarbonyl in dry benzene. The resulting complexes (172) can be recrystallised from ether at -70". In polar solvents these compounds react with a wide variety of aryl vinyl and alkyl halides (reactivity I > Br > C1) as illustrated by the formation of (173) from a-methyl- ally1 bromide (172; R = Me) and p-dibromobenzene. The intramolecular coupling of dihalides is a traditional route to cyclo- alkanes. A number of examples of this reaction reported this year show that with suitable reaction conditions good yields can be obtained.Thus 1,3- dihaloalkanes with alkali-metal vapour yield' 36 1,3-alkadiyl radicals which cyclise to cyclopropanes in yields up to 88 %. 1,3-Di-iodopropane with benzoyl peroxide or t-butyl peroxide gives 9Crl00% yieldsi3' of cyclopropane by a radical induced y-elimination reaction. No mechanistic details are available but it appears a synthetically useful reaction 1,5'di-iodopentane giving cyclo- pentane. 1,4-Dibromobutane with lithium amalgam in refluxing dioxan givesi3* cyclobutane in 70% yield; a ten-fold increase on the best reported yield with sodium metal; analogously cyclopentane is formed in 75,% yield. Electrolysis of 1,4-dibromobutane (in dimethylformamide-Bu",N ClO,) yields'39 cyclobutane (25%) but cyclopentane could not be prepared from 1,5-dibromopentane.The synthesis of large-ring 1,5-dienes (175; n = 6 8 and 12) can be a~hieved'~' by the cyclisation of allylic dibromides (174; n = 6 8 and 12)with nickelcarbonyl and a large variety of dihalides (76)can be cyclised in good yield to (176) by their reaction with triphenylphosphinemethylene." A completely different route to a cyclic compound is the peroxide-catalysed addition of methylene iodide to alkenes to yield cyclopropanes. This reaction has been applied142 to a large number of alkenes but as yet there is no informa- tion regarding the mechanism of the reaction which appears to be related to the known photochemical addition of methylene iodide to alkenes. Miscellaneous.-The insertion reaction of dichlorocarbene occurs with a very specific preference for C-H bonds located p to either silicon tin or mercury.The insertion of dichlorocarbene into the optically active mercury compound (S)-(-X178) proceeds with net inversion of configuration to yield the product (179) as is shown by conversion of the latter into the (S)-(-)-acid (180). This is an unprecedented stereochemical result from a divalent carbon insertion process. Any mechanistic path which involves direct attack of the divalent carbon atom on the carbon-hydrogen bonding electrons is clearly impossible.'43 Carbon atoms produced in a carbon arc are efficient deoxygenation agents as might be expected since the heat of combination of an oxygen atom with a 136 R.G. Doer and P.S. Skell J. Amer. Chem. SOC.,1967,89,4684. 13' L. Kaplan J. Amer. Chem. SOC. 1967,89 1753. 13' D. S. Connor and E. R. Wilson Tetrahedron Letters 1967,4925. 139 M. R. Rifi J. Amer. Chem. Soc. 1967,89,4442. 140 E. J. Corey and E. K. W. Wat J. Amer. Chem. SOC.,1967,89,2757. 14' H. J. Bestmann and E. Kranz Angew. Chem. 1967,79,95. 14f L. Kaplan J. Amer. Chem. SOC. 1967,89,4566. K. A. Landgrebe and D. E. Thurman J. Amer. Chem. SOC.,1967,89,4542. Aliphatic Compounds 27 1 HI Me I Me I I(Et-C-Me CHzhHg I(Et -C- CHJ2Hg CH C12 IEt -C.CH CO,H aCO2H (178) (179) (1 80) L+c-co+U + SCHEME P-%+C-co+ J Hg(NzC.C02Et)2 C-COzEt COzEt 0 0 carbon atom is 256.7 cal./mole.144 Examples of such reactions which are carried out at low temperature ca.-196” in the condensed phase are shown in Scheme 15. Although the chemistry of carbon atoms as well as di- and trivalent carbon intermediates has been investigated little is known about monovalent carbon intermediates. The scarcity of information on this class of carbon intermediates is related to the difficulty in generating them under conditions amenable to mechanistic study. It is now reported’45 that photolysis of diethyl mercury- bis(diaz0acetate) (181) yields ethoxycarbonylmethyne (182) as a doublet. With cyclohexene it undergoes both insertion and addition reactions to give intermediate radicals which by hydrogen abstraction lead to the products (183) and (194). A ‘compound’ which is partially aliphatic in character is (185) in which the terminal substituents of the open-chain component are too bulky to allow it to slip through the ring.It was prepared’46 by tritylation of decane-1,lO-diol in the presence of a 30-membered cyclic acyloin. Only minute quantities of Ph I /CH-c\ 144 P. S. Skell J. H. Plonka R. R. Engel J. Amer. Chem. SOC.,1967,89 1749. 14’ ThapDo Minh H. E. Gunning 0.P. Stransz J. Amer. Chem. SOC., 1967,89,6785. I. T. Harrison and S. Harrison J. Amer. Chem. SOC.,1967,89,5723. 272 M. F. Ansell the diol are tritylated while being threaded through the macrocycle. However by bonding the macrocycle by way of its half ester with succinic acid to a resin and then by repeatedly (70 times) treating the resin bonded macrocycle with a solution of the diol trityl chloride dimethyl formamide and pyridine a 6% yield of this chromatographical separable product was obtained.The name hooplane is suggested for this class of compound.