Tetrahydrofurans, 2-ethynyl

Toluene is a useful co-solvent in metal-ammonia reductions as first reported by Chapman and his colleagues. The author has found that a toluene-tetrahydrofuran-ammonia mixture (1 1 2) is a particularly useful medium for various metal-ammonia reductions. Procedure 8a (section V) describes the reduction of 17-ethyl-19-nortestosterone in such a system. Ethylene dibromide is used to quench excess lithium. Trituration of the total crude reduction product with methanol affords an 85% yield of 4,5a-dihydro-17-ethyl-19-nortestosterone, mp 207-213° (after sintering at 198°), reported mp 212-213°. For the same reduction using Procedure 5 (section V), Bowers et al obtained a 60% yield of crude product, mp, 196-199°, after column chromatography of the total reduction product. A similar reduction of 17-ethynyl-19-nortestosterone is described in Procedure 8b (section V). The steroid concentration in the toluene-tetrahydrofuran-ammonia system is 0.05 M whereas in the ether-dioxane-ammonia system it is 0.029 M. 

Acetylene is passed for 1 hr through a mixture consisting of 0.5 g (72 mg-atoms) of lithium in 100 ml of ethylene-diamine. A solution prepared from 1 g (3.5 mmoles) of rac-3-methoxy-18-methylestra-l,3,5(10)-trien-I7-one and 30 ml of tetrahydrofuran is then added at room temperature with stirring over a period of 30 min. After an additional 2 hr during which time acetylene is passed through the solution the mixture is neutralized with 5 g of ammonium chloride, diluted with 50 ml water, and extracted with ether. The ether extracts are washed successively with 10% sulfuric acid, saturated sodium hydrogen carbonate and water. The extract is dried over sodium sulfate and concentrated to yield a solid crystalline material, which on recrystallization from methanol affords 0.95 g (87%) of rac-3-methoxy-18-methyl-17a-ethynyl-estra-l,3,5(10)-trien-17jB-ol as colorless needles mp 161°. 

Reaction vessels used in this procedure were flame dried under vacuum and all operations carried out in an oxygen-free, argon or nitrogen atmosphere. To a solution of 465.7 mg (2.3019 mmol) of 4,4-dimethyl-6-ethynyl-thiochroman in 4 ml of dry tetrahydrofuran at 0°C was added dropwise 1.5 ml of 1.6 M (2.4 mmol) n-butyl lithium in hexane. This was stirred at 0°C for 10 min and at room temperature for 10 min, cooled again to 0°C and then treated with a solution of 330 mg (2.4215 mmol) of fused ZnCI2 in 4 ml dry tetrahydrofuran using a double ended needle. Thereafter the... 

The treatment of the thermodynamic enolate of 2-methylcyclohexanone with ethynyl(phenyl)iodonium tetrafluoroborate in tetrahydrofuran affords 2-ethynyl-2-methylcyclohexanone (equation 267). This is the only example known to this author of the alkynylation of an unactivated monocarbonyl compound with an alkynyliodonium salt. However, the earlier conclusion that simple enolates do not undergo alkynylation with alkynyliodonium salts (section II.D.7 and II.G) needs to be revvised. 

The coupling of /raaf-2,6-diodo-3,7-diphenyltetrathiafulvalene 704 (obtained in 62% yield by metallation of the corresponding diphenyl-TTF with LDA followed by iodination with perfluorohexyl iodide) with trimethylsilylacetylene in the presence of Pd(PPh3)4, Cul, and NEt3 in tetrahydrofuran (THF) afforded symmetrical bis(2-trimethylsilyl)ethynyl-TTF 705 in 70% yield which was then desilylated with aqueous KOFI to give 706 (Scheme 104) <1998S259>. 

Reductions of most monochlorocyclopropanes have been carried out using an alkali metal in liquid ammonia or in an alcohol containing a small amount of water, butyllithium followed by aqueous workup, and zinc in a protic solvent. When butyllithium and alkali metals are employed, halogen atoms elsewhere in the molecule can also react. Thus, treatment of 1-chloro-l-trichIorovinyl-2,2,3,3-tetramethylcyclopropane (4) with excess of butyllithium afforded, after hydrolysis, 1 -ethynyl-2,2,3,3-tetramethylcyclopropane (5) in 43% yield. When the same compound was reacted with lithium in a mixture of tetrahydrofuran and moist rerr-butyl alcohol, 2,2,3,3-tetramethyl-l-vinylcyclopropane (6) and l-ethylidene-2,2,3,3-tetramethylcyclopropane... 

Ethynyl-substituted tetrahydrofurans can be ring-opened via transfer hydrogenation using 10 mol% of TpRuPPhjfMeCNljPF (Tp = tris(l-pyrazolyl)borate) to provide the dienyl ketone in high yield. An example is illustrated below <04JOC4692>. 

Na-acetylide in xylene added under argon to a soln. of 40 g. 3-methoxy-2,5(10)-estradiene-17-one in dimethylformamide, stirred 15 min. at room temp., acetic anhydride added with vigorous stirring, which is continued for 1 min. -> 21 g. 3-methoxy-17a-ethynyl-2,5(10)-estradien-17j -of 17-acetate. Also in tetrahydrofuran s. E. Shapiro, L. Finckenor, and H. L. Herzog, J. Org. Chem. 33, 1673 (1968). 

Polymerization of propynaldehyde (CH=C-CH=0) is also unique. In dimethylformamide at O °C with sodium cyanide or with tri-n-butyl phosphine catalysts, the reactions yield polymers composed of two different structural units. One is a polyaldehyde and the other is a polyacetylene. The reaction in tetrahydrofuran, however, at -78 °C with sodium cyanide catalyst results in a crystalline poly(ethynyl oxymethylene). Radical initiated polymerizations of this monomer at 60 °C, on the other hand, proceed through the acetylenic group only. 

A convenient stereospecific synthesis under mild conditions of terminal acetylenes from olefins via the treatment of lithium ethynyl-trialkylborates with iodine has recently been published. Carboxyl groups, including sterically hindered ones and those of a-amino acids can be conveniently and selectively reduced to alcohols with borane in tetrahydrofuran . Homoallylic alcohols have been dehydrated to the... 

The lack of diastereoselectivity in the reaction was disappointing, and a closer inspection reveals some details. The separated diastereoisomers of complex 5c, dicobalt hexacarbonyl-5-ethynyl-2-(4-nitrophenyl)tetrahydrofuran-3, 3-dicarboxylic acid dimethyl ester, were treated individually with BF3 OEt2 in dichloromethane at room temperature. In both cases, the single diastereoisomer was transformed to a 1 1 mixture. This indicates that the diastereoisomers are very close in thermodynamic stability and that the ratio achieved under the reaction conditions is close to the thermodynamic... 

Acetylene passed slowly into a soln. of Li-naphthalene in tetrahydrofuran to give Li-acetylide quantitatively, then j -ionone added ethynyl-/ -ionol. Y 90%. - This is a convenient procedure for the ethynylation of a,y -unsatd. ketones under very mild conditions. F. e. s. K. Suga, S. Watanabe, and K. Takahashi, Chem. Ind. 1967, 1748 Can. J. Chem. 46, 3041 (1968) 2-acetylene-1,4-diols s. Chem. Ind. 1968, 1489. 

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