Reduction, of alkynes

Alkynes are reduced to trans-alkenes under dissolving-metal conditions. 

There are several ways to perform the cis reduction of alkynes. For example, catalytic hydrogenation using a poisoned catalyst and hydroboration followed by protonation yields ds-alkenes. For examples and mechanism, see Chapter 6, section 6.2. 

Straus, D. A., Encyclopedia of Reagents for Organic Synthesis, Wiley, New York, 2000. 

Alkynes undergo many of the same addition reactions as alkenes. For example, alkynes wiU undergo catalytic hydrogenation just as alkenes do  

In the process, the alkyne consumes two equivalents of molecular hydrogen  

Under these conditions, the cis alkene is difficult to isolate because it is even more reactive toward further hydrogenation than the starting alkyne. The obvious question then is whether it is possible to add just one equivalent of hydrogen to form the alkene. With the catalysts we have seen thus far (Pt, Pd, or Ni), this is difficult to achieve. However, with a partially deactivated catalyst, called a poisoned catalyst, it is possible to convert an alkyne into a cis alkene (without further reduction)  

There are many poisoned catalysts. One common example is called Lindlar s catalyst Lindlar s catalyst =, Pd / BaS04, CH3OH 

An energy diagram showing the effect of a poisoned catalyst. Hydrogenation of the alkyne is catalyzed, but subsequent hydrogenation of the alkene is not catalyzed. 

Alkynes are reduced to alkanes by addition of Hz over a metal catalyst. The reaction occurs in two steps through an alkene intermediate, and 

Complete reduction to the alkane occurs when palladium on carhon (Pd/C) is used as catalyst, hut hydrogenation can he stopped at the alkene stage if the less active Lindlar catalyst is used. The Lindlar catalyst is a finely divided palladium metal that has heen precipitated onto a calcium carbonate support and then deactivated by treatment with lead acetate and quinoline, an aromatic amine. The hydrogenation occurs with syn stereochemistry (Section 8.5), giving a cis alkene product. 

The alkyne hydrogenation reaction has been explored extensively by the Hoffmann-LaRoche pharmaceutical company, where it is used in the commercial synthesis of vitamin A. The cis isomer of vitamin A produced initially on hydrogenation is converted to the trans isomer by heating. 

An alternative method for the conversion of an alkyne to an alkene uses sodium or lithium metal as the reducing agent in liquid ammonia as solvent. This method is complementary to the Lindlar reduction because it produces 

Mechanism of the lithium/ammonia reduction of an aikyne to produce a trans alkene. 

Reduction of an alkyne adds H2 to one or both of the n bonds. There are three different ways by which the elements of H2 can be added to a triple bond. 

When an alkyne is treated with two or more equivalents of H2 and a Pd catalyst, reduction of both n bonds occurs. Syn addition of one equivalent of H2 forms a cis alkene, which adds a second equivalent of H2 to form an alkane. Four new C-H bonds are formed. By using a Pd-C catalyst, it is not possible to stop the reaction after addition of only one equivalent of H2. 

Problem 12.10 Which alkyne has the smaller heat of hydrogenation, HC = CCH2CH2CH3orCH3C = CCH2CH3 Explain your choice. 

Palladium metal is too active a catalyst to allow the hydrogenation of an alkyne to stop after one equivalent of H2. To prepare a cis alkene from an alkyne and H2, a less active Pd catalyst is nsed—Pd adsorbed onto CaCOs with added lead(ll) acetate and quinoline. This catalyst is called the Lindlar catalyst after the chemist who first prepared it. Compared to Pd metal, the Lindlar catalyst is deactivated or poisoned.  

With the Lindlar catalyst, one equivalent of H2 adds to an alkyne, and the ds alkene product is unreactive to further reduction. 

Decreasing the number of degrees of unsaturation increases the melting point. 

When an oil is partially hydrogenated, some double bonds react with H2, whereas some double bonds remain in the product. 

Partial hydrogenation decreases the number of allylic sites, making a triacylglycerol less susceptible to oxidation, thereby increasing its shelf life. 

Draw the products formed when triacylglycerol A is treated with each reagent, forming compounds B and C. Rank A, B, and C in order of increasing melting point. 

Interactive to use a web-based palette to predict products for alkyne reduction reactions. 

O Lithium metal donates an electron to the alkyne to give an anion radical. .. 

Hydrogenolysis can occur using dissolving metal conditions, and is particularly useful for the cleavage of O-benzyl and N-benzyl derivatives. It is widely used as a useful alternative to catalytic hydrogenation. Treatment with sodium in ammonia cleaves the O-benzyl group, as in the conversion of 491 to 492 (in 90% yield), in Mulzer s synthesis of hastanecine. l Note that the byproduct is toluene. It is also possible to cleave other reactive C—O (or C—N) bonds. Allylic acetates, for example, are cleaved to the hydrocarbon, as shown by the reaction of 493 with lithium and ammonia to give an 81% yield of 494.  

Since the mechanism involves electron transfer to a heteroatom rather than carbon, vinyl, and aryl derivatives can be easily reduced under these conditions. Many functional groups can be reduced, depending on their ability to accept an electron. Cyclopropane rings are opened under these conditions. The bridging cyclopropane moiety in 498, for example, was opened with lithium and ammonia to give 499 in 85% yield, as 

The hydroboration/oxidation sequence is complementary to the direct, mercury(II)-catalyzed hydration reaction of a terminal alkyne because different products result. Direct hydration with aqueous acid and mercury(Il) sulfate leads to a methyl ketone, whereas hydroboration/oxidation of the same terminal alkyne leads to an aldehyde  

Problem 8.6 What alkyne would you start with to prepare each of the following compounds by a hydroboration/oxidation reaction  

Complete reduction to the alkane occurs when palladium on carbon (Pd/C) is used as catalyst, but hydrogenation can be stopped at the alkene 

As was discussed in Sections 11.1.5 and 11.2.3, the stereoselective partial hydrogenation of alkynes to either cis or trans alkenes is of key importance. Chemical reductions can also be applied to achieve both selective transformations. 

It was observed in 1941 that with sodium in liquid ammonia, called dissolving-metal reduction, different dialkylacetylenes were converted to the corresponding trans alkenes in good yields and with high selectivity 195 

The observation was a significant finding since at the time, when the only synthetic method to reduce alkynes selectively was their conversion by heterogeneous catalytic hydrogenation (Raney nickel) to cis alkenes. The dissolving-metal reduction provided easy access to high-purity trans alkenes since the latter do not readily react further under the conditions used. The efficient reduction of 1-alkynes in this system requires the presence of ammonium ion.196 

The electron transfer to the acetylenic bond forms the frans-sodiovinyl radical 20 that, after protonation, produces tram radical 21. At low temperature (—33°C) in the presence of excess sodium, the conversion of the trans radical to sodiovinyl intermediate 22 is slightly more rapid than the conversion of the tram radical to the cis radical 23 (21 — 22 22 — 23). As a result, protonation yields predominantly the trans alkene. However, low sodium concentration and increased temperature lead to increasing proportion of the cis alkene. Although other dissolving-metal reductions are less thoroughly studied, a similar mechanism is believed to be operative.34 Another synthetically useful method for conversion of alkynes to trans alkenes in excellent yields is the reduction with CrS04 in aqueous dimethylforma-mide.198 

Besides heterogeneous and homogeneous catalytic hydrogenations, chemical reductions can also transform alkynes to cis alkenes. Interestingly, activated zinc in the presence of a proton donor (alcohol), although a dissolving-metal reagent, reduces disubstituted alkynes to cis alkenes 199 

In 1945, Campbell and McDermott [32] found that the reduction of diaUcylacety-lenes by calcium hexamine [CafNI-Isle] in diethyl ether yielded the corresponding trans alkenes. In 1984, Benkeser and Belmonte [33] reported results from detailed studies of the reduction of internal and terminal alkynes by calcium in a mixture of methylamine and ethylenediamine (1 1 v/v). For example, reduction of 4-oc-tyne gives a mixture of isomeric trans octenes in 75% overall yield it includes trans-2-, 3-, and 4-octenes in the ratio 1 9 88. Treatment of 1-heptyne, a terminal alkyne, with a fivefold excess of calcium produces 70% of a mixture containing 87% n-heptane, 7% tra s-2-heptene, and 3% 1-heptene. 

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Stereoselective and chemoselective semihydrogenation of the internal alkyne 208 to the ew-alkene 210 is achieved by the Pd-catalyzed reaction of some hydride sources. Tetramethyldihydrosiloxane (TMDHS) (209) i.s used in the presence of AcOH[116]. (EtO)3SiH in aqueous THF is also effective for the reduction of alkynes to di-alkenes[l 17], Semihydrogenation to the d.v-alkene 211 is possible also with triethylammonium formate with Pd on carbon[118]. Good yields and high cis selectivity are obtained by catalysis with Pd2fdba)3-Bu3P[119],... 

The stereochemistry of metal-ammonia reduction of alkynes differs from that of catalytic hydrogenation because the mechanisms of the two reactions are different The mechanism of hydrogenation of alkynes is similar to that of catalytic hydrogenation of alkenes (Sections 6 1-6 3) A mechanism for metal-ammonia reduction of alkynes is outlined m Figure 9 4... 

The mechanism by which the Birch reduction of benzene takes place (Figure 118) IS analogous to the mechanism for the metal-ammonia reduction of alkynes It involves a sequence of four steps m which steps 1 and 3 are single electron transfers from the metal and steps 2 and 4 are proton transfers from the alcohol... 

The special salt effect is a constant feature of the activation of substrates in cages subsequent to ET from electron-reservoir complexes. In the present case, the salt effect inhibits the C-H activation process [59], but in other cases, the result of the special effect can be favorable. For instance, when the reduction of a substrate is expected, one wishes to avoid the cage reaction with the sandwich. An example is the reduction of alkynes and of aldehydes or ketones [60], These reductions follow a pathway which is comparable to the one observed in the reaction with 02. In the absence of Na + PFg, coupling of the substrate with the sandwich is observed. Thus one equiv. Na+PFg is used to avoid this cage coupling and, in the presence of ethanol as a proton donor, hydrogenation is obtained (Scheme VII). 

The masked propargylic anfz-l,3-diols obtained in these reactions are useful precursors to more functionalized systems. Lindlar reduction of alkyne 171 generated the (Z)-allylic diol 172, which underwent diastereoselective osmium tetraoxide-catalyzed dihydroxylation to provide the partially protected tetraol 173 (Scheme 28). The propargylic anfz-l,3-dioxane 175,obtained in 88% yield from... 

Schemes 6-30 A plausible reaction pathway for lr(l)-catalyzed reduction of alkynes with MeOH...

Partial reduction of alkynes to Z-alkenes is an important synthetic application of selective hydrogenation catalysts. The transformation can be carried out under heterogeneous or homogeneous conditions. Among heterogeneous catalysts, the one that... 

Scheme 5.7 illustrates these and other applications of the hydride donors. Entries 1 and 2 are examples of reduction of alkyl halides, whereas Entry 3 shows removal of an aromatic halogen. Entries 4 to 6 are sulfonate displacements, with the last example using a copper hydride reagent. Entry 7 is an epoxide ring opening. Entries 8 and 9 illustrate the difference in ease of reduction of alkynes with and without hydroxy participation. 

F. Sato developed titanium (Il)-based c/s-reduction of alkynes as shown in Scheme 5 [14], and the method was applied to the synthesis of pheromones by Kitching (Scheme 6) [15]. This titanium (Il)-based reaction gives pure (Z)-alkenes. Kitching summarized the contemporary methods for the synthesis of skipped polyynes and their reduction to skipped polyenes [15]. 

Kitching employed the titanium (Il)-based czs-reduction of alkynes in their synthesis of (3 ,8Z,llZ)-3,8,ll-tetradecatrienyl acetate (9), the pheromone of the moth Scrobipalpuloides absoluta as shown in Scheme 15 [15]. 

Supplemental References for Table 2. Organosilane Reduction of Alkynes... 

A few remarkable, but rather uncommon, transfer hydrogenations also deserve mention within the context of this chapter namely, the reduction of alkynes to alkenes using a chromium catalyst, and the reduction of double bonds using diimines. 

Scheme 20.29 Reduction of alkynes to trans-alkenes by chromous sulfate.

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