Acetylides double bonds from

The addition of acetylides to oxiranes yields 3-alkyn-l-ols (F. Sondheimer, 1950 M.A. Adams, 1979 R.M. Carlson, 1974, 1975 K. Mori, 1976). The acetylene dianion and two a -synthons can also be used. 1,4-Diols with a carbon triple bond in between are formed from two carbonyl compounds (V. Jager, 1977, see p. 52). The triple bond can be either converted to a CIS- or frans-configurated double bond (M.A. Adams, 1979) or be hydrated to give a ketone (see pp. 52, 57, 131). 

A multi-step reaction sequence was then realized to prepare the precursor (178) for the pivotal macrocyclization reaction. Alternate stepwise chain elongations were achieved according to Schemes 28 and 29. Reaction of the tosylate prepared from the alcohol 162 with lithium acetylide afforded the alkyne 174 (Scheme 28). Following the introduction of a tosylate at the upper branch, a one-carbon chain elongation of the terminal alkyne afforded the methyl alkynoate 175. A methyl cuprate 1,4-addition was used to construct the tri-substituted C double bond stereoselectively. For this purpose, the alkynoate 175 was initially transformed into the Z-configured a,/ -unsat-... 

Attack from the more open backside leads to formation of the a-acetylide. Mild hydrolysis of the enol ether function then affords the unconjugated ketone ethynodrel (14-5), This first oral contraceptive to reach the market has become better known as The Pill . The double bond in that product moves into conjugation on treatment with strong acid, forming ethynodrone (14-6), the second contraceptive pill to reach pharmacy shelves. 

The synthesis of the fragment C3-C13 was achieved in five steps from 169. Treatment of the tosylated stereotetrad 169 with 5 equivalents of lithium acetylide in DMSO led an acetylenic compound which was treated with ra-Buli and methyl iodide, and then reduced by Na/NH3 to produce the E-geometry of the C12-C13 double bond with concomitant removal of the PMB group at C5, giving the primary alcohol 170 (49% yield for the three-step sequence). Swern oxidation of 170 gave the corresponding aldehyde which was involved in an Evans-type asymmetric aldol reaction with the boron enolate A to produce the adduct 171 (dr > 95/5, 90% yield). (Scheme 33). 

The reactions of acetylene which have been mentioned are analogous to those of the unsaturated hydrocarbons containing a double bond. Acetylene and other compounds which contain a carbon atom in combination with hydrogen and joined to a second atom in the manner which is represented by a triple bond, that is, those containing the group H —C =, show characteristic properties which serve to distinguish them from other substances. Such compounds are converted into metallic derivatives when they are treated with an ammoniacal solution of cuprous chloride or of silver chloride. If acetylene is passed into a solution of cuprous chloride in ammonia, a red precipitate is formed which has the composition C2CU2. This compound, which is a carbide of copper, is usually called copper acetylide. It explodes, when dry, if it is struck or is heated to 100°-120°. When treated with hydrochloric acid or with a solution of potassium cyanide, acetylene is formed. 

Finally, mention must be made of a short paper by Faranov et al. who have departed from the study of vinylic monomers and have produced cathodic-ally, by an anionic mechanism, oligomers of both phenylacetylene and diphenyl-acetylide which contain conjugated double bonds. 

In the remainder of this chapter, particular reactions are selected for examination of their synthetic potential. Acetylide ions are useful for linking carhon chains, particularly where a double bond is desired with stereoselectivity. Acetylene and 1-alkynes may be deprotonated with strong bases such as LDA and then treated with alkyl halides or carbonyl compounds. Preformed lithium acetylide complexed with ethylenediamine is available as a dry powder. Several alkynes derived from acetylide and carbon dioxide or formaldehyde are available, including propargyl alcohol (HC CCHjOH), propargyl bromide (HC CCH Br), and methyl propio-late (HC=CC02CH3). 

The addition of polar organometallics onto carbon-nitrogen double bonds opens a versatile entry to amines. Lithium acetylides often require activation by boron trifluoride to display full reactivity. Azomethines derived from crotyl or cinnamyl... 

Isomerization also results when sodium amide is used as the base in the double dehydrohalogenation. All possible triple-bond isomers are formed, but sodium amide is such a strong base that it deprotonates the terminal acetylene, removing it from the equilibrium. The acetylide ion becomes the favored product. When water is added to quench the reaction, the acetylide ion is protonated to give the terminal alkyne. 

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