Dissolving-metal reduction alkynes

Dissolving-Metal Reduction of Aromatic Compounds and Alkynes. Dissolving-metal systems constitute the most general method for partial reduction of aromatic rings. The reaction is called the Birch reduction,214 and the usual reducing medium is lithium or sodium in liquid ammonia. An alcohol is usually added to serve as a proton source. The reaction occurs by two successive electron transfer/proto-nation steps. 

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... 

Reduction of an alkyne to an (E)-alkene can be achieved by treating the alkyne with lithium or sodium metal in ammonia at low temperatures (Following fig.). This is called dissolving metal reduction. 

Na, or Li in liquid ammonia, for example) to reduce aromatic rings and alkynes. The dissolving metal reduction of enones by lithium metal in liquid ammonia is similar to these reactions—the C=C bond of the enone is reduced, with the C=0 bond remaining untouched. An alcohol is required as a proton source and, in total, two electrons and two protons are added in a stepwise manner giving net addition of a molecule of hydrogen to the double bond. 

The partial reduction of alkynes provides methods that are both regio-and stereospecific. Dissolving metal reductions tend to give trans alkenes, whereas catalytic methods of reduction generate the cis alkenes (Scheme 3.3). A Lindlar catalyst (Pd/CaCOj + PbO, partially poisoned with quinoline) has been recommended for use in this context. 

Although catalytic hydrogenation is a convenient method for preparing cis alkenes from alkynes, it cannot be used to prepare trans alkenes. With a dissolving metal reduction (such as Na in NH3), however, the elements of H2 are added in an anti fashion to the triple bond, thus forming a trans alkene. For example, 2-butyne reacts with Na in NH3 to form rram-2-butene. 

Dissolving metal reduction of an alkyne with Na, NH3 to form a trans alkene (12.5C)... 

Dissolving Metal Reduction of an Alkyne to a Trans Alkene 435... 

For reduction, relevant data from polarographic and cyclic voltammetric experiments are summarized in Tables 1 and 2, respectively. For the results in Table 1 the variety of solvents and reference electrodes used makes comparisons difficult. It is clear, however, that even with the activation of a phenyl substituent (entries 6,7,9-14) reduction occurs at very cathodic potentials. In this context it is worth noting that in aprotic solvents at ca. — 3 V vs. S.C.E.) it becomes difficult to distinguish between direct electron transfer to the alkyne and the production of the cathode of solvated electrons. Under the latter conditions the indirect electroreductions show many of the characteristics of dissolving metal reductions (see Section II.B). Even at extreme cathodic potentials it is not clear that an electron is added to the triple bond the e.s.r. spectra of the radical anions of dimesitylacetylene and (2,4,6,2, 4, 6 -hexa-r-butyldiphenyl)acetylene have been interpreted in terms of equal distribution of the odd electron in the aromatic rings . 

Both disubstituted alkynes (Chapter 3.3, this volume) and isolated terminal double bonds may be reduced by alkali metals in NH3, but isolated double bonds are usually stable to these conditions. However, 16,17-secopregnanes (10 equation 8) afford mixtures of cyclization products (11) and (12) in 61% to 80% yield with Na naphthalenide-THF, Na-NHs-THF, Na-THF or Li-NHs-THF. With Na-NHa-THF-r-butyl alcohol, a 91% yield of a 72 28 mixture of (11) (12) (R = Me) is obtained. This type of radical cyclization of alkenes and alkynes under dissolving metal reduction conditions to form cyclopentanols in the absence of added proton donors is a general reaction, and in other cases it competes with reduction of the carbonyl group. Under the conditions of these reactions which involve brief reaction times, neither competitive reduction of a terminal double bond nor an alkyne was observed. However, al-lenic aldehydes and ketones (13) with Li-NHs-r-butyl alcohol afford no reduction products in which the diene system survives. ... 

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). ... 

Catalytic hydrogenation of an enone would not be chemoselective if an isolated double bond were also present in the molecule. However, isolated double bonds are inert to dissolving metal reduction. On the other hand, a variety of functional groups are reduced with alkali metals in liquid ammonia. These include alkynes, conjugated dienes, allylic, or benzylic halides and ethers. 

Semireduction of internal alkynes in the presence of a transition metal catalyst (e.g., Ni2B, Pd/C) provides disubstituted cw-alkenes. On the other hand, dissolving metal reduction of alkynes or reduction of propargylic alcohols with LiAlH4 or with Red-Al [sodium bis(2-methoxyethoxy)aluminum hydride] furnishes tran -disubstituted alkenes. ... 

The two hydrogen atoms add to the opposite faces of the alkene (i.e. anti-addition) using sodium in liquid ammonia. This dissolving metal reduction produces a solvated electron, which adds to the alkyne to produce a radical anion (bearing a negative charge and an unpaired... 

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

Fig. Reduction of alkyne to a (Z)-alkyne. Dissolving Metal Reduction...

Dissolving metal reductions work because the electrons released as reactive metals form soluble cations that can be harnessed to do other, more useful, reductions. Electrons are the simplest possible reducing agents, and they will reduce carbonyl compounds, alkynes, or aromatic rings—in fact any functional group with a low-energy n orbital into which the electron can go. 

The alkyne was then reduced to an E alkene by a dissolving metal reduction, a step which also hydrolysed the five-membered heterocycle. The next step, an epoxidation, is needed to install the third of the chiral centres at the left-hand end of penarisidlne. However, hydrogen-bond directed epoxidation of this allylic alcohol would be expected to give the syn product shown, which has the wrong relative stereochemistry between the brown OH group and the epoxide. 

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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