Ethoxyacetylene1

[927-80-0]  · C4H6O  · Ethoxyacetylene  · (MW 79.09)

(preparation of alkenylcuprates,2 anhydrides,3 ketenes,4,5 lactones;6 reacts with allylboranes7)

Alternate Name: ethyl ethynyl ether.

Physical Data: bp 48-50 °C; d 0.800 g cm-3 (0.745 g cm-3 in hexane).

Solubility: sol alcohol, ether, benzene, hexane.

Preparative Methods: from chloroacetaldehyde diethyl acetal (70%).8,9

Form Supplied in: 50 w/w % solution in hexane(s).

Handling, Storage, and Precautions: moisture sensitive; potential fire hazard with certain metal salts.8 Use in a fume hood.

Cycloaddition Reactions.

Ethoxyacetylene (1) participates in [2 + 2], [4 + 2], and 1,3-dipolar cycloaddition reactions. Diels-Alder reactions with oxazinones give substituted 3,5-disubstituted 2,6-dichloropyrimidines (eq 1).10 1,3-Dipolar cycloaddition reactions with aldoximes (eq 2)11 and with nitrile oxides12 give isoxazoles.

Ethoxyacetylene and its derivatives thermally decompose to generate ketenes4,5,13 which either add to themselves or undergo further cycloaddition reactions. In addition, other ketenes, such as dimethylketene, add to (1) to give cyclobutanone derivatives (eq 3).14

Ethoxyacetylene gives pyrazoles with Diazomethane, triazoles with aryl and substituted alkyl azides, 2-quinolines with aryl isocyanates, and o-ethoxyphenylacetylene with benzyne.1 Phospholes may be prepared in a [2 + 2 + 1] cycloaddition of a terminal phosphinidene complex with (1).15 Organometallic reagents add to ethoxyacetylene to give 1,4-naphthoquinone-cobalt16 and 2H-pyrrole-tungsten complexes,17 and phenols.18

Nucleophilic Additions to Ethoxyacetylene.

Vinyl anions can be generated by nucleophilic addition to ethoxyacetylene. Alkyl cuprates tend to transfer only one group while (Z)-alkenyl cuprates transfer both groups to give (E)-a,b-unsaturated ketones after hydrolysis of the initial enol ethers (eq 4).19 These vinylcopper reagents have been coupled, condensed with alkyl and vinyl iodides, acid chlorides, vinylogous acid chlorides, and iodine to give a variety of derivatives.2

Trimethylsilylmethylcopper adds to ethoxyacetylene with cis addition to give allylic silane (2) that, when quenched with electrophiles, gives (E)-3-substituted 2-alkoxy-2-alkenylsilanes (eq 5).20

Arylcopper reagents extend this chemistry. Thus, by coupling a Grignard reaction with a Wacker oxidation, 1,4-diketones can be prepared (eq 6).21

Nucleophilic Reactions of Ethoxyacetylene.

Anions derived from ethoxyacetylene, generated as the Grignard reagent,22 or lithium8,23 or aluminum24 salts, add to alkyl halides,25 aldehydes, ketones, and epoxides22 to give precursors of a-hydroxy ketones,26 aldehydes, acids, or a,b-unsaturated esters. Cyclohexene epoxide and ethoxyacetylene give a lactone upon treatment of the intermediate alcohol with acid. Conversion to the alane is necessary as no ring opening occurs with lithium ethoxyacetylide (eq 7). This methodology is superior to that which uses lithium t-butylacetate (Rathke's salt), which fails to react with hindered epoxides.24

Ethoxyacetylene reacts with aldehydes and ketones in the presence of Boron Trifluoride to give a,b-unsaturated esters.27

Acylation Reactions.

Amines can be acylated by ethoxyacetylene to give carboxylic acid derivatives in good yields.13 1-Ethoxyvinyl esters, which are useful as acylating agents, have been prepared from carboxylic acids and ethoxyacetylene in a RuII-catalyzed reaction.28 Cyclic anhydrides have been formed by dehydrating diacids with (1) (eqs 8 and 9).3,29 Weakly nucleophilic 2-fluoro-2,2-dinitroethanol yields bis(2-fluoro-2,2-dinitroethyl)ethoxy ethyl orthoester in a 95% yield in a HgII-catalyzed reaction with ethoxyacetylene.30

Lactones have been prepared by thermolysis of adducts formed from lithium ethoxyacetylide and hydroxy ketones (eq 10). Higher reaction temperatures increase conversion and lower reaction times. Good yields are reported for five-, six-, and seven-membered rings. Larger macrocycles (9-, 10-, 15-membered) require Bu3N as a catalyst to get respectable yields and to minimize oligomeric products (see also 2-Chloro-1-methylpyridinium Iodide).6

Insertion Reactions.

Allyl(dialkyl)boranes react with ethoxyacetylene to give dialkyl(alkoxypentadienyl)boranes which may be converted to 2-alkoxy-1,4-pentadienes7 or methyl allyl ketone31 on protonolysis. In a one-pot reaction, triallylboranes and ethoxyacetylene give 1,4-pentenynes as shown in eq 11.7 Similar chemistry is observed with tribenzylboranes.31 The ethoxyacetylene/(iodo-9-BBN) adduct reacts with acyclic a,b-unsaturated ketones to give d-keto esters (74-95%)32 and with aryl aldehydes to give cinnamic esters (89% yield, 99% (E)).33 Unlike Wittig chemistry, this methodology tolerates base-sensitive functional groups. In a Mercury(II) Acetate catalyzed reaction, ethoxyacetylene, diphenylboronic acid, and alkyl or aryl aldehydes give b-hydroxy and b-acetoxy esters.34

Transition Metal Catalyzed Reactions.

Zirconium reagents catalyze a one-pot addition of ethoxyacetylene to aryl iodides or bromides to give (E)-b-ethoxyalkene derivatives (eq 12). A variety of functional groups are tolerated on the aryl halide (Cl, OMe, CN, CO2Me).35 This chemistry has been extended to indoles.36 Ethoxyacetylene gives pyrones with CO2 and Bis(1,5-cyclooctadiene)nickel(0),37 and indenols with acetophenone and PhCH2Mn(CO)5.38

Miscellaneous Synthetic Transformations.

Ethoxyacetylene has been used to prepare substituted acylketenes,39 (alkoxyethynyl)phosphonites,40 and alkoxy metal carbenes.41


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Kenneth C. Caster

Union Carbide Corporation, South Charleston, WV, USA



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