Alkynes acetylides from

A good example is the synthesis of a substituted alkyne starting from acetylene (ethyne) itself. One alkylation uses NaNH2 as the base to make sodium acetylide and the other uses BuLi to make a iithium acetylide. 

A formal [3 + 2] cydoaddition route leading to the preparation of di- and tri-substituted indoles 264 from ortho-haloanilines 261 and copper(I) acetylides 262 was introduced by Castro (Scheme 9.92) [75, 76, 111], simultaneously with the mentioned earlier coupling-cyclization reaction en route to benzofurans 57 (Scheme 9.21). It is believed that this stoichiometric in copper cascade reaction proceeded with the generation of an intermediary ortho-alkynylaniline 263 [77]. Attempts to turn this reaction into a more practical catalytic process, using basic conditions to generate Cu(I)-acetylide from a terminal alkyne in the presence of Cul, provided poor yields of the respective indoles 264. 

FIGURE 7.95 Formation of an acetylide from a terminal alkyne. 

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). 

This reaction process takes advantage of the ease with which a copper acetylide will oxidatively insert into an alkynyl halide bond. The postulated mechanism begins with and in situ base- and Cu(I)-induced formation of a copper acetylide (1) from a terminal alkyne (33). This intermediate undergoes oxidative addition into the activated C-X bond of an alkynyl halide (34) to afford the copper(III) species 35. Reductive elimination of the bis-alkyne 32 from complex 35 delivers the reaction product and regenerates the copper(l) halide 36 which may re-enter the catalytic cycle. 

Jiao et al. developed a Cul- and AgCOg-cocatalyzed synthesis of pyrazolo[l,5- ] pyridine derivatives via dehydrogenative annulations of pyridinium ylide and terminal alkynes (Scheme 8.68). Ag2C03 might assist the formation of copper acetylide from alkyne with Cu(I) catalyst. The C(sp)-H bond of alkyne... 

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). 

The properties of organometallic compounds are much different from those of the other classes we have studied to this point Most important many organometallic com pounds are powerful sources of nucleophilic carbon something that makes them espe cially valuable to the synthetic organic chemist For example the preparation of alkynes by the reaction of sodium acetylide with alkyl halides (Section 9 6) depends on the presence of a negatively charged nucleophilic carbon m acetylide ion... 

We won t study the details of this substitution reaction until Chapter 11 but for now can picture it as happening by the pathway shown in Figure 8.6. The nucleophilic acetylide ion uses an electron pair to form a bond to the positively polarized, electrophilic carbon atom of bromomethane. As the new C-C bond forms, Br- departs, taking with it the electron pair from the former C-Br bond and yielding propyne as product. We call such a reaction an alkylation because a new alkyl group has become attached to the starting alkyne. 

Because of its generality, acetylide alkylation is an excellent method for preparing substituted alkynes from simpler precursors. A terminal alkyne can be prepared by alkylation of acet dene itself, and an internal alkyne can be prepared by further alkylation of a terminal alkyne. 

An alkyne is a hydrocarbon that contains a carbon-carbon triple bond. Alkyne carbon atoms are sp-hybridized, and the triple bond consists of one sp-sp a bond and two p-p tt bonds. There are relatively few general methods of alkyne synthesis. Two good ones are the alkylation of an acetylide anion with a primary-alkyl halide and the twofold elimination of HX from a vicinal dihalide. 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

Formation of Alkynes, Alkenes, and Ketones from Boranes and Acetylides... 

When acetylene and real alkynes are in contact with copper, silver and transition metals, they form acetylides and analogues that are explosive, from ambient temperature upwards for acetylides. For instance, acetylene that was accidentally in the presence of electrical wires whose copper was bare led to a detonation. 

The effect of stoichiometry, substituent, and temperature were investigated in reactions between the hydride HCo(tdppep) (19) and a number of alkynes.175 The cr-acetylide complex (20) and the (7-alkenyl (21) are formed from the stoichiometric reaction with ethyl propiolate. However, when a ten-fold excess of ethyl propiolate is used, the acetylide complex is formed quantitatively and one equivalent of alkyne is hydrogenated to alkene. Forcing conditions and a large excess of... 

This work was extended to include acetylides (alkynyls) of the type (RNG)Au-G=C-C6H4-/)-C H2 +1, with n — 6-12 (even numbers), and R as above. The compounds were prepared from (tht)AuCl and the alkynes /)-HC=C-C6H4-C H2 +1 in aqueous acetone with soda as a weak base. The resulting insoluble, polymeric alkynylgold(i) complexes were dissolved in an organic solvent by adding equivalent quantities of the isocyanides. All products show distinct transitions from a crystalline to a smectic A phase and finally to the isotropic melts.206... 

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-... 

The metal vinylidene intermediates discussed elsewhere in this chapter are limited to a single carbon-substituent on account of the 1,2-migration process by which they form from terminal alkynes. Alkenylidenes—vinylidenes bearing two carbon-substituents—are formed by nucleophilic addition of the (i-carbon of a metal acetylide to an electrophile (Scheme 9.16) [30]. 

Finally, the peculiar formation of iodoalkynes from iodine and acetylenes with relatively low (< 25) pK values in liquid ammonia should be mentioned [121]. The most likely intermediates occurring are acetylide "anions" formed in very low concentrations from the acetylene and the base ammonia. The conversions proceed very slowly and iodinadon of the lithiated alkynes in the same solvent is undoubtedly a far superior method. 

Terminal alkynes are acidic, and the end hydrogen can be removed as a proton by strong bases (e.g. organolithiums, Grignard reagents and NaNH2) to form metal acetylides and alkynides. They are strong nucleophiles and bases, and are protonated in the presence of water and acids. Therefore, metal acetylides and alkynides must be protected from water and acids. 

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