Mechanism dissolving metal reduction

We therefore use a dissolving metal reduction in strong acid. This reaction, the Clemmensen reduction, may use the principle we have outlined here, but its mechanism is unknown in detail. R2C = 0 + Zn/Hg + cone. HC1— )RaCH2... 

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... 

The mechanism has a good deal in common with a whole class of reductions, of which the Clemmensen is a member, known as dissolving metal reductions. We shall now look at these as our third (after metal hydrides and catalytic hydrogenation) important class of reducing agents. 

The stereochemical course of these, and other similar reductions, led Barton to suggest that dissolving metal reductions of ketones and oximes to secondary alcohols and primary amines would lead to mixtures of products rich in the thermodynamically more stable product. However, in the early 1960s a number of reports appeared in which the reduction of ketones gave primarily the thermodynamically less stable epimeric alcohol. These observations have prompted a continuing series of investigations into the mechanism of these reductions. 

It was suggested in the 1950s that the reduction of aliphatic ketones by dissolving metals proceeded by two sequential one-electron additions to provide a dianion (equation 1). This mechanism was based on the observation that benzophenone affords a dianion on reaction with excess Na in liquid NH3, and it was inferred that aliphatic ketones would behave similarly. A number of workers presented mechanistic rationalizations for the stereochemical course of the dissolving metal reductions of cyclic aliphatic ketones based on this dianion concept. However, in a 1972 review, it was noted that the reduction potentials of alkali metals were not sufficient to effect the addition of two electrons to an aliphatic carbonyl group, and an alternative mechanism was suggested which with some modification is now generally accepted. ... 

The vast majority of the dissolving metal reductions of carbonyl compounds which have been carried out synthetically have used either alcohols or liquid NH3 as the solvent. " However, a variety of other solvents have been employed, frequently in connection with studies of the mechanism of the reductions or in exploratory synthetic studies. 

The reduction of bicycloheptanones, particularly camphor (1) in the absence of added proton donors has been studied extensively in connection with the mechanism of the dissolving metal reductions and are discussed in Section 1.4.2.2. As previously noted, reductions under these conditions are of considerably less utility in synthesis than those carried out in the presence of a relatively acidic proton donor (NH4CI or ethanol). 

There is apparently only one report of the dissolving metal reduction of thioketones thiobenzophe-none (107) has been reduced with excess Na-THF to give dianion (108), which on acidification gave thiol (109). The thiol was not isolated, but was oxidized with iodine to give the corresponding disulfide in 65% overall yield. The mechanism of the reduction is suggested to be the sequential addition of two electrons to the thiocarbonyl, which was confirmed by electron spin resonance spectroscopy studies of the intermediate thioketyl, and trapping dianion (108) with a variety of electrophiles. ... 

The mechanism of dissolving metal reductions depends on the nature of the solvent and the nature of the substrate. The proposed mechanism for the reduction of dialkylacetylenes by sodium in HMPA in the presence of a proton donor is illustrated in equation (18). The addition of an electron to the triple bond of (45) is proposed to produce the rran -sodiovinyl radical (46), or the corresponding radical anion (47), which undergoes protonation by the added alcohol to produce the radical (48). Further reduction of (48) by sodium produces the rrans-sodiovinyl compound (49), which on protonation produces the trans-a -kene (50). In the absence of a proton donor, the reduction of (45) with sodium in HMPA results in the formation of a mixture of cis- and trans-2- and 3-hexenes. Control studies showed that the isomerization products 2- and 3-hexene are not formed by rearrangement of the cis- or frans-3-hexenes. It was concluded that the starting alkyne (45) acts as a reversible proton donor reacting with an intermediate anion or radical anion to produce the delocalized anion (51) which is then protonated to produce the al-lene (52). Reduction of the allene (52), or further rearrangement to the alkyne (53) followed by reduction, then leads to the formation of the mixture of the cis- and trans-2- and 3-hexenes (equation 19). ... 

A radical anion can lose an anionic leaving group to give a neutral free radical, and in the reverse direction, a neutral free radical can combine with an anionic nucleophile to give a new radical anion. A radical cation can also combine with a nucleophile. Such steps occur in the SrnI mechanism (Chapter 2), in dissolving metal reductions, and in oxidative deprotections. These two-electron reactions have obvious counterparts in carbocation chemistry. 

Problem 5.11. Draw a mechanism for the dissolving metal reduction of acetophenone (PhCOMe) to ethylbenzene and thence to l-ethyl-l,4-cyclohexadiene. 

In Section 6.8, you saw the mechanism for the dissolving-metal reduction that converts an alkyne to a trans alkene. 

A MECHANISM FOR THE REACTION ] The Dissolving Metal Reduction of an Alkyne 322... 

This reaction, called a dissolving metal reduction, takes place in solution and produces an )- or rwwr-alkene. The mechanism involves radicals, which are molecules that have unpaired electrons (see Chapter 10). 

The Birch reduction is a dissolving metal reduction, and the mechanism for it resembles the mechanism for the reduction of alkynes that we studied in Section 7.15B. A sequence of electron transfers from the alkali metal and proton transfers from the alcohol takes place, leading to a 1,4-cyclohexadiene. The reason for formation of a 1,4-cyclohexadiene in preference to the more stable conjugated 1,3-cyclohexadiene is not understood. 

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