Synthesis of Alkynes from Acetylides

Predict the products of the following acid-base reactions, or indicate if no significant reaction would take place. 

The second approach forms the triple bond by a double dehydrohalogenation of a dihalide. This reaction does not enlarge the carbon skeleton. Isomerization of the triple bond may occur (see Section 9-8), so dehydrohalogenation is useful only when the desired product has the triple bond in a thermodynamically favored position. 

An acetylide ion is a strong base and a powerful nucleophile. It can displace a halide ion from a suitable substrate, giving a substituted acetylene. 

If this S 2 reaction is to produce a good yield, the alkyl halide must be an excellent S 2 substrate It must be primary, with no bulky substituents or branches close to the reaction center. In the following examples, acetylide ions displace primary halides to form elongated alkynes. 

If the back-side approach is hindered, the acetylide ion may abstract a proton, giving elimination by the E2 mechanism. 

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Introduction 392 9-2 Nomenclature of Alkynes 393 9-3 Physical Properties of Alkynes 394 9-4 Commercial Importance of Alkynes 395 9-5 Electronic Structure of Alkynes 396 9-6 Acidity of Alkynes Formation of Acetylide Ions 397 9-7 Synthesis of Alkynes from Acetylides 399 9-8 Synthesis of Alkynes by Elimination Reactions 403 Summary Syntheses of Alkynes 404 9-9 Addition Reactions of Alkynes 405... 

A general one-pot procedure for the synthesis of alkynes from aldehydes (Corey-Fuchs reaction) that involves the synthesis of the triphenylphosphonium dibromomethane reagent has been explored by Michel and coworkers. In general, the base of choice is f-BuOK, but in case of the N-Boc piperidine, use of BuLi in order to avoid unwanted side reactions between the carbamate and the acetylide function provides a cleaner reaction at low temperature (eq 64). 

A synthesis of dienediynes from 2-(hydroxymethylene)cyclopentanone involves the di-enol ditriflate [bis(trifluoromethanesulphonate)] 120, which reacts with an alkyne in the presence of a palladium catalyst to give 121, accompanied by only small amounts of the regioisomer 122. The major product on treatment with the same or different alkyne yields the dienediyne 123 2-(Alkyn-l-yl)-l-methylpyrrolidines 125 (R = Me, pentyl, MesSi or Ph) have been obtained from the thiolactam 124 by sequential alkylation, treatment with a lithium acetylide and reduction with LAH. The phenylthio group in a-(phenylthio)-lactams is displaced by an alkynyl group by the action of an alkyn-l-ylzinc chloride or of di(alkyn-l-yl)zinc compounds. Thus the j -lactam 126 gave 127 and the azaprostacyclin II 128 gave 129 1... 

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. 

Fig. 16.30. Pd(0)-catalyzed arytation of a copper acetytide at the beginning of a three-step synthesis of an ethynyt aromatic compound. Mechanistic details of the C,C coupling Step 1 formation of a complex between the catalytically active Pd(0) complex and the arylating agent. Step 2 oxidative addition of the arylating agent and formation of a Pd(II) complex with a cr-bonded aryl moiety. Step 3 formation of a Cu-acetylide. Step 4 trans-metalation the alkynyl-Pd compound is formed from the alkynyl-Cu compound via ligand exchange. Step 5 reductive elimination to form the -complex of the arylated alkyne. Step 6 decomposition of the complex into the coupling product and the unsaturated Pd(0) species, which reenters the catalytic cycle anew with step 1.

A typical example of such reactions of 1-alkynyltrialkylborates is demonstrated in the synthesis of internal acetylenes. When 1-alkynyltrialkylborates (18), readily prepared from lithium acetylides and trialkylboranes, are treated with iodine, the corresponding internal alkynes are obtained in almost quantitative yields (Eq. 39)... 

Other nucleophiles that have been used in this context are acetylides (alkynes). The addition of those to iminium cations generated in situ from aldehydes and secondary amines accomplishes a gold(III)-catalyzed three-component coupling for the synthesis of propargylamines, as can be observed in equation (124). The reactions are performed in water or in tetrahydrofuran (THF) when supported catalysts are employed.Chiral prolinol derivatives as... 

Additional developments in the synthesis of enediyne motifs, beyond the now well-established Pd-catalyzed routes, have recently been reported. Casey et al. (377, 399) demonstrated that cw-enediyne complexes can be readily obtained via dimerization of Cp(CO)2Re-aIkynylcarbene complexes at 100°C (cf. Fig. 27), as well as from the addition of a,oc)-diynes to manganese carbyne complexes that rearrange to enediynes below room temperature. In parallel, Cummins and co-workers have demonstrated that sequential reductive coupling of Mo(IV) acetylides and alkyne metathesis can also be used as a novel route to both ( )- and (Z)-enediyne constructs (523). 

As noted above, alkyne anions are very useful in Sn2 reactions with alkyl halides, and in acyl addition reactions to a carbonyl.46 Alkyl halides and sulfonate esters (tosylates and mesylates primarily) serve as electrophilic substrates for acetylides. A simple example is taken from Kaiser s synthesis of niphatoxin B, in which propargyl alcohol (36) is treated with butyllithium and then the OTHP derivative of 8-bromo-1-octanol to give a 47% yield of 37.48... 

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. 

Loreau synthesized the cis-9,trans- -, trans- 0,cis- 2-, and ar-10,a r-12-CLA using 1,2-dichloroethene (22). The synthesis of cis-9, trans- -C Js started from 7-bromoheptane-l-ol which was first blocked with a protecting group before lithium acetylide was added to yield 2-(non-8-ynyloxy)tetrahydro-2H-pyran. This first building block was attached to trans-1,2-dichloromethane by using conventional alkyne... 

Equations 13.10-13.12 show three examples of the synthesis of vinylidene complexes by reactions of metal-acetylide complexes with acid or base. The molybdenum(II) acetylide complex in Equation 13.10 reacts with acid to protonate the p-carbon and generate a cationic vinylidene complex. In this case, the vinylidene complex is thermodynamically unstable. Warming to 0 °C leads to rearrangement of this species to the tautomeric alkyne complex. In contrast, the more electron-rich molybdenum-acetylide complex in Equation 13.11 containing three phosphite donors generates a vinylidene complex upon addition of a proton from alumina to the 3-carbon of the acetylide. The vinylidene form of the complex is apparently more stable than the alkyne complex in this case. 

Because of the ready availability of acetylene and the ease with which it is converted to a nucleophile, alkylation of acetylide anions is the most convenient laboratory method used for the synthesis of other alkynes. The process can be repeated, and a terminal alkyne in turn can be converted to an internal alkyne. An important feature of this reaction is that a new carbon-carbon skeleton can be made, allowing for the construction of larger carbon skeletons from smaller ones. In the following scheme, the carbon skeleton of 3-heptyne is constructed from acetylene and two lower-molecular-weight haloalkanes. 

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