CHAPTER 1
Acetylenes, Allenes, and Olefins
BY R. S. ATKINSON
1 Acetylenes
Areas of acetylenic chemistry reviewed recently include the base-catalysed isomerization of acetylenes, nucleophilic additions to acetylenes, additions to activated triple bonds, synthetic and naturally occurring acetylene compounds as drugs, allenic and acetylenic carotenoids, linear polymers from acetylenes, carbonylation of mono-olefinic and monoacetylenic hydrocarbons, and the combustion and oxidation of acetylene. Several books have also appeared.
Synthesis. — The coupling reaction between acetylenic Grignard reagents and allylic halides yields acetylenic olefins which are of value for sterospecific conversion into acyclic isoprenoid polyenes. However, this coupling reaction generally leads to mixtures of allenic and acetylenic products. The lithiated trimethylsilylacetylene has been used to circumvent this problem. Another complementary method is trimethylsilylation of the crude reaction product after treatment with one equivalent of Grignard reagent. Thus the allylic dibromide (1) gives the trimethylsilylated acetylene (2), from which the enediyne (3) is obtained in 50% overall yield.
Selenium dioxide oxidation of aryl ketone semicarbazones (4) in acetic acid affords 1,2,3-selenadiazoles (5). Pyrolysis of the latter gives selenium and the arylacetylenes (6) in good yield. The same procedure has been used to prepare cyclo-octyne in 34% yield.
The fragmentation reaction of Eschenmoser, which gives acetylenes from toluene-p-sulphonyl hydrazones of αβ-epoxy-ketones (Scheme 1), has been adapted to the synthesis of acetylenes from ketones substituted with leaving groups in the α-position [(7) [right arrow] (8)].
Cadiot–Chodkiewicz coupling of 1-bromoacetylenes with terminal acetylenes in the presence of cuprous salts and amines is much slower when 1-chloroacetylenes are used. Conditions have been described for the intra-molecular coupling of the bromodiyne (9) to (10) in 40% yield using high dilution and complementing the Glaser reaction.
Labile and unstable acetylenes are conveniently coupled with halogeno-acetylenes as their copper(II) salts. The terminal acetylenes required, e.g. (11), can be obtained by deformylation with base of the aldehydes obtained by nickel peroxide oxidation of the corresponding alcohols (12). Iodopyrazoles, iodopyridines, and iodonitrobenzenes couple efficiently with acetylenes in the presence of copper, potassium carbonate, and pyridine. Copper acetylides also react with allylic halides to give ene-ynes (13) and the reaction is accelerated by the presence of halide or cyanide ion. Similarly, reaction with acid chlorides giving acetylenic ketones (14) is catalysed by halide salts and by addition of hexamethylphosphortriamide at a specific time during the reaction.
A synthesis of p,p'-bridged tolans (15) has used the Fritsch–Buttenberg –Wiechell (FBW) rearrangement of gem-dihalogeno-olefins with strong base. The effect of diminishing n upon the u.v. spectrum of (15) has been determined and for the o,p'-bridged acetylene and p,p'-bridged diacetylenes. The FBW rearrangement has also been used to prepare dicyclopropylacetylene from (16) with n-butyl- lithium.
Conversion of terminal olefins into alk-l-ynes by a bromination-dehydro-bromination sequence is often easier in theory than in practice. The use of DMSO as solvent and methylsulphinyl carbanion or sodamide as the base gives excellent yields with little isomerization to alk-2-ynes. Moreover, conditions have also been found for transformation of alk-1-ynes into alk-2 -ynes.
Selective hydroboration of symmetrical conjugated diynes with dialkyl-boranes provides a route to acetylenic ketones in yields >70%. Protonolysis of the intermediate boranes also gives the corresponding cis-ene-ynes in high yield (Scheme 2).
Reaction between acetylenic Grignard reagents and hydroximoyl chlorides (17) is known to give isoxazoles via intermediate ketoximes (18). The latter have now been isolated by working at low temperature. In 4,4,4-triethoxy-but-1-yne (19), obtained from propargylmagnesium bromide and tetraethyl orthocarbonate, the carboxy-group, masked as an orthoester, is protected from attack by basic reagents, and ready acetylene-allene interconversion is inhibited. Thus the lithio-derivative of (19) is acylated and converted into enol-ether (20) by base-catalysed addition of alcohols. This represents extension of carboxylic acid R by two acetyl units.
A safe and convenient preparation of dichloroacetylene uses a liquid medium and reduces explosion hazards. All the six homo- and hetero-dihalogenoacetylenes (21) have been obtained pure and characterized by their i.r. and Raman spectra. Chlorofluoroacetylene has also been synthesized by base treatment of 1,1-dichloro-2-fluoroethylene (22). It is a very unstable explosive compound which adds regiospecifically to ethers in the absence of initiators. Trichloroethylene reacts with AW-disubstituted lithium amides and secondary amines to form chloroketen aminals (23). Upon further treatment with strong base, the latter undergo HCl α-elimination and 'onium' rearrangement to afford yne-diamines (24) in high yields.
Acetylenic sulphoxides and sulphones are obtained by oxidation of the more readily available acetylenic sulphides using m-chloroperbenzoic acid at -20 °C in chloroform. Alternatively, the sulphoxides may be prepared by dehydrohalogenation of chlorovinylsulphoxides (25). A useful preparative route to acetylenic acids (26) uses aroylmalonates as starting materials. Treatment with arenesulphonic anhydrides yields the intermediate enol sulphonates, and decarboxylative elimination of the derived diacids gives (26) in 80% overall yields.
The synthesis of the hexadehydro[18]annulene (27), and hence of [18]-annulene, has been improved. Although cycloheptyne has not been isolated, the thiacycloheptyne (29) has been prepared in low yield by oxidation of bishydrazone (28).
Asymmetric synthesis of acetylenic alcohols is possible by reduction of the corresponding ketones with lithium aluminium hydride complexed with sugar derivatives; the optical yields are 4–7%. The trimethylether of the naturally occurring robustol (30), from the leaves of Grevillea robusta A. Cunn., has been synthesized in 55% yield via cupric acetate oxidative cyclization of the diacetylene (31).
Cycloaddition Reactions. — The use of dimethylacetylene dicarboxylate (DMAD) in cycloaddition reactions with various substrates is illustrated in the Table.
1,2,3-Trimethylindole and DMAD yield the benzazepine (32) and the dienone (33); the suggested mechanism is shown in Scheme 3. A reaction similar to the formation of benzazepines from indoles accounts for cycloaddition of nitroacetylenes to cyclic enamines, affording the ring-opened nitrocycloheptadienylamine (34), which can be hydrolysed to the cycloheptenone with acid.
The product from the reaction of nitroacetylene (35) with ynamine (36) is not the stabilized cyclobutadiene (37) but the isomeric nitrile oxide (38). The nucleophilic ynamines also cycloadd to carbonyl groups and to acyclic imines to give acrylamide and acrylamidines, respectively (Scheme 4); cyclic imines give the two-carbon ring expansion.
Cycloaddition of acetylenes with various substituted isocyanates follows a diversity of pathways depending on the substitution of both reactants. Thus cycloaddition of the ethynylogous acid amide (39) with N-carbonylisocyanates gives oxazinones (40). By contrast, one mole of N-benzoylisocyanate reacts with one mole of ethyl propiolate to yield (41), but in a 2:1 molar ratio with 3-methoxypropyne to yield (42). The extremely electrophilic halogenosulphonylisocyanates react differently again: (43) reacts with but-2-yne in a 2 : 1 molar ratio to give (44) whereas X-ray analysis shows the structure of the product from chlorosulphonylisocyanate and hex-3-yne to be (45).
1,3-Dipolar addition of cyanoacetylene to the ylide (46) gives the cyanoindolizine (47), dehydrogenation being effected by the acetyleneF2 The 1,3-dipolar addition of azlactones (48) to DMAD proceeds via prior tautomerism to the mesoionic oxazolium 5-oxide (49); pyrroles are the products of subsequent elimination of carbon dioxide.
The Diels–Alder addition product (50) from butadiene and 1,2-dibenzoyl-acetylene is a versatile precursor for preparation of isoindoles, isobenzo-furans, and isobenzothiophens.
Other Additions to the Acetylenic Bond. — Nucleophilic. Acetophenone oxime and DMAD react to yield the 1:1 adduct (51), which undergoes a Claisen-type rearrangement on heating to the pyrrole (52). Similarly, the adduct (53) from phenylamidoxime and DMAD is thermally rearranged to the imidazolone (54). The driving force in both these rearrangements is the making of a C — C bond at the expense of breaking a N — O bond. Adducts (55) of N-allylanilines with DMAD also undergo a hetero-Cope rearrangement to give anilinofumarates, which are converted into quinolones (56) under the conditions of the reaction.
The stereochemistry of nucleophilic addition to activated triple bonds is related to the nature of the activating groups. In the case of the trifluoromethyl substituted acetylenes where activation is by the inductive effect alone, addition is predominantly trans, e.g. methoxide-catalysed addition of methanol to hexafluorobut-2-yne gives (57), trans-Addition is also observed in the nucleophilic addition of thiols to ethylsulphonylacetylene to give (58) in a kinetically controlled reaction; isomerization at 100 °C gave the trans products (59).
Copper alkyls, prepared from RMgBr and CuBr, react with terminalalkynes to give dienes (60) by two successive sterospecific additions. No metal–hydrogen exchange occurs in ether and the reaction can be limited to the first step; bubbling oxygen into the solution promotes the coupling reaction whose stereospecificity is illustrated by the reactions (1) and (2). The vinylcopper intermediate (61) is identified by hydrolysis with D2O to give the deuterio-olefin (62) or by iodination to provide iodo-olefins, mono- or di-substituted on C-2 (63) and (64). The more reactive allyl bromide may also add to the intermediate copper complex [reaction (3)].
Addition of Grignard reagents to alkenes and alkynes is known to be promoted by the presence of hydroxy-functions near the multiple bonds. The stereochemistry of addition appears to be trans [e.g. (65)] with cis-addition products resulting from a side-reaction — probably addition to an allenol (66) formed by Grignard-promoted isomerization of the alkynol. The trans-addition eliminates a mechanism such as (67). Similarly, suitably located tertiary amine functions can cause addition of Grignard reagents to otherwise unreactive multiple bonds, e.g. (68) [right arrow] (69).
Electrophilic. Electrophilic addition of bromine to acetylenes has received much less attention than the corresponding reaction with olefins. At low bromine concentration and in the absence of bromide ion, the rate of bromination of ring-substituted phenylacetylenes correlates well with σ+ values. The ρ value of –5.17 is interpreted in terms of a transition state leading to a vinyl cation intermediate (70) and, in agreement, addition is non-stereospecific. In contrast, a cyclic bromonium ion is postulated in alkylacetylene bromination with the isolation of trans-dibromides from hex-3-ynes and hex-1-ynes.
A kinetic and product study of the reaction of diphenylacetylenes with triphenylaluminium is interpreted as monomeric aluminium attacking the acetylene electrophilically in the rate-determining step (71); cis-Addition products are obtained. Vinylalanes, formed by addition of aluminium alkyls to acetylenes, are known to add to disubstituted acetylenes to produce trans,trans-dienes, e.g. (72), after hydrolysis. Terminal alkynes do not undergo this reaction owing to metalation, but the derived terminal alanes (73) are also converted by cuprous chloride into isomerically pure trans,trans-dienes (74). Hydroalumination has also been used to convert alk-1-ynes into alkylcyclopropanes and trans-2-alkyl-1-halogeno-cyclopropanes (75), cleavage of the carbon-aluminium bond occurring with retention of configuration.
Monohydroboration of terminal alkynes with bulky hydroboranes (76) places the boron exclusively at the terminal position of the triple bond. Addition to unsymmetrically disubstituted alkynes is markedly affected by the triple bond substituent size. Protonolysis or oxidation with H2O2 converts the alkynes into alkenes and ketones (aldehydes), respectively. Hydroboration of hex-1-yne with bis(trans-2-methylcyclohexyl)borane (77) gives the vinylborane (78). Treatment of (78) successively with 6N-NaOH and iodine gave (79) in 85 % yield. Migration of the cyclohexyl group occurs with retention of configuration at the ring. Inversion at the migration terminus is known from previous work. A complementary method for introducing trans-olefinic groups on to cycloalkane rings is treatment of α-halogenovinylboranes (80) with sodium methoxide followed by protonolysis.
The products of addition of sulphur dichloride to diphenylacetylene are strongly dependent on the solvent. In ether, the unstable vinylsulphenyl chloride (81) is formed, which readily cyclizes to the benzothiophen (82). In methylene chloride, the divinylsulphide (83) is formed exclusively.
Reaction of 5-halogenopent-1-yne or 6-halogenohex-2-yne with trifluoroacetic acid gives predominantly the 1,4-halogen shifted product (84). Addition of HX to the double bond is trans and provides a general method for preparation of trans-unsymmetrical vinyl halides, which are themselves synthetically useful.
In the presence of superacids, alkynes generate vinyl cations which are trapped by carbon monoxide. Thus a mixture of but-2-yne and carbon monoxide, when bubbled into FSO3H–SbF5 in an n.m.r. tube, gave (85), (86), and (87) (Scheme 5); (85) was explained by attack of adventitious water. Curiously, the stereochemistry of (86) implies attack of carbon monoxide upon the more hindered side of the (presumably linear) vinyl cation intermediate. The methyl migration required to explain (87) is also unexpected. Vinyl cations are also involved in the reaction of t-butylacetylene with anhydrous HL1 at room temperature (Scheme 6); (88) and (89) are minor products from cyclodimerization of the vinyl cation intermediate.
Acid-catalysed intramolecular cyclization of (90) gives the enone (91). None of the isomeric (92) was obtained, although it is stable under the reaction conditions.
Acetylenic bond participation occurs in the biogenetic-like cyclizations (93) [right arrow] (94) and (95) [right arrow] (96), the vinyl cation in the former case being trapped by ethylene carbonate.
Acetolysis of 1,3-di-t-butylpropargyl tosylate (97) shows an eight-fold rate enhancement by comparison with a model compound (98). The major products were the acetate (99) and the rearranged olefins (100) and (101). None of the other products was allenic: hence the positive charge density resides mostly at C-1 in the propargyl cation.
Radical Addition. Free-radical addition of toluene-p-sulphonyl iodide or methanesulphonyl iodide to acetylenes proceeds readily and stereoselectively when the two are mixed in ether and illuminated. The high yields of crystal-line products (102) obtained imply that in the mechanism (Scheme 7), chain transfer by the sulphonyl iodide (k3) is much faster than isomerization of the intermediate vinyl radical (k2). The trans-addition was confirmed by zinc-acetic acid reduction to the sulphone, and by X-ray analysis of one of the adducts.
The kinetically controlled radical addition of ethyl mercaptan to ethoxy-acetylene is also trans and sterospecific at low conversions to give cis-1-ethoxy -2-(ethylthio)ethylene (103).
In the peroxide-catalysed reaction of pentamethyldisilane with pentamethyl-disilanylacetylene, abstraction of hydrogen from an intermediate vinyl radical (104) must occur to account for acetylene (105) as one of the products. Trialkylboranes are known to undergo facile 1,4-addition to many αβ-olefinic carbonyl compounds. Acetylacetylene does not react spontaneously with trialkylboranes but the radical reaction, as in the case of β-substituted olefinic carbonyl compounds, may be induced by the presence of catalytic amounts of oxygen. Hydrolysis of the intermediate allenic compound (106) produces αβ-unsaturated methyl ketones in good yield.
Addition of benzyne to tricyclo[4,1,0,02,7]heptane (107) gives the formal [σ2 π2 + δ2] cycloaddition product (108) in 61 % yield. The mechanism is believed to involve a biradical intermediate (109) with attack on the C-1 — C-7 bond taking place from inside the 'flap' as shown, a feature which is characteristic of these reactions. Dicyanoacetylene reacts with (110) to form (111), and in principle attack takes place here inside the 'flap' at either a or b. The isolation of (111) shows that reaction has occurred at b and that the initial radical addition is fairly sensitive to steric effects
Other Reactions of Acetylenes. — Several recent papers have been concerned with the mechanism of nucleophilic displacement at acetylenic carbon. In the halide displacement from halogenoacetylenes, substitution is feasible by either α-addition and β-elimination [reaction (4)] or by attack on the halogen atom with subsequent attack by the acetylide anion [reaction (5)]. Viehe and Delavarenne have suggested a third possibility which includes β-addition, α-elimination, and 'onium' rearrangement [reaction (6)] similar to the mechanism of the Frisch–Buttenberg–Wiechell rearrangement. Their evidence is that addition of thiophenolate anion in protonic solvents to t-butylchloroacetylene gives (112) and (113). The latter are thermodynamically unstable with respect to (114) but all three isomers yield the acetylene (115) on treatment with lithium diethylamide. This acetylene is also obtained on addition of thiophenolate anion to t-butylchloroacetylene in aprotic solvents, and the inference is that the mechanism in reaction (7) is operating, assuming that a drastic change in mechanism does not occur with absence of proton-donating solvents. The validity and generality of this mechanism remains to be proved.
