1.4- Cyclohexadienes. from Birch reduction

Because the reactions of related in -cyclohexadienyl complexes are synthetically valuable, the reactions of this ligand have been studied extensively. An outline of how this chemistry can be conducted on the Fe(CO)j fragment is shown in Equation 11.51. A variety of cyclohexadienes are readily available from Birch reduction of substituted aromatics. Coordination and abstraction of a hydride, typically by trityl cation, leads to cationic cyclohexadienyl complexes. These cyclohexadienyl complexes are reactive toward organolithium, -copper, -cadmium, and -zinc reagents, ketone enolates, nitroal-kyl anions, amines, phthalimide, and even nucleophilic aromatic compounds such as indole and trimethoxybenzene. Attack occurs exclusively from the face opposite the metal, and exclusively at a terminal position of the dienyl system. This combination of hydride abstraction and nucleophilic addition has been repeated to generate cyclohexa-diene complexes containing two cis vicinal substituents. The free cyclohexadiene is ttien released from the metal by oxidation with amine oxides. ... 

Birch reduction-methylation of the 2,3-dialkyl substituted benzamide 85 (Scheme 19) provided the cyclohexa-1,4-diene 86 with diastereoselectivity comparable to that observed with the 2-alkylbenzamides illustrated in Scheme 4. Cyclohexadiene 86 was converted to iodolactone 87 and reduction of 87 with BusSnH occurred with exclusive equatorial delivery of hydrogen to give the axial methoxyethyl derivative 88. Lactone 88 was converted to the Caribbean fruit fly pheromone (+)-epia-nastrephin 90 (> 98% ee) in 9.5% overall yield from the chiral benzamide 85. °... 

Therefore, using either direct Birch reduction alkylation or Birch reduction-protonation-enolate formation alkylation, both followed by auxiliary removal, it is possible to prepare either enantiomer of a desired 2,5-cyclohexadiene-l -carboxylic acid derivative in excellent enantiomeric purity from the same starting materials. 

Perhaps it should be mentioned also the orientation of the Birch reduction which is strongly dependent on the nature of the aromatic substituents. Donor-substituted benzenes furnish predominantly 1-substituted 1,4-cyclohexadienes while acceptor-substituted analogues give 3-substituted 1,4-cyclohexadienes. The regioselectivities can be explained by the destabilizing d-d pairing in the intermediates from d-substi-tuted cyclohexadienyl radical anions leading to the 3-substituted products, and the... 

Fig. 14.71. Birch reduction of benzenes give 1,4-cyclohexadienes. The radical anion C is formed by capture of a solvated electron in an antibonding 7r orbital of an aromatic compound. The alcohol protonates this radical anion to the radical D, which captures another electron from the solution to form the carbanion E. The carbanion is protonated by a second equivalent of the alcohol, and the 1,4-dihydroaromatic compound results.

A special case involves complexes of cyclohexadienyl ligands, which may result from the addition of nucleophiles to r)6-arene complexes (Section 7.7) or hydride abstraction from complexes of readily available cyclohexadienes (Birch reduction of arenes) (Figure 7.14). In the latter case, it is within the chemistry of iron that such complexes find the widest... 

Carboxylic acids can be transformed into alkenes when they contain a leaving group like H (Scheme 12), SiMea, SPh or CO2H in the -position. The alkene is formed by an 1-elimination from the intermediate carbocation. Some examples are summarized in Table 10. The decarboxylative elimination of l,4-cyclohexadiene-6-carboxylic acids (Table 10, entry 2) is part of a useful method for the alkylation of aromatic compounds. This involves first a reductive alkylation using a Birch reduction, which is then fol-... 

Birch reduction of aromatic ethers is well known to afford alicyclic compounds such as cyclohexadienes and cyclohexenones, from which a number of natural products have been synthesized. Oxidation of phenols also affords alicyclic cyclohexadienones and masked quinones in addition to C—C and/or C—O coupled products. All of them are regarded as promising synthetic intermediates for a variety of bioactive compounds including natural products. However, in contrast to Birch reduction, systematic reviews on phenolic oxidation have not hitherto appeared from the viewpoint of synthetic organic chemistry, particularly natural products synthesis. In the case of phenolic oxidation, difficulties involving radical polymerization should be overcome. This chapter demonstrates that phenolic oxidation is satisfactorily used as a key step for the synthesis of bioactive compounds and their building blocks. 

The first step of a Birch reduction is a one-electron reduction of the aromatic ring to a radical anion. Sodium is oxidized to the sodium ion Na. This intermediate is able to dimerize to the dianion. In the presence of an alcohol the second intermediate is a free radical which takes up another electron to form the carbanion. This carbanion abstracts another proton from the alcohol to form the cyclohexadiene. 

The principle of least motion, which states that the reaction that involves the least change in atomic positions or electronic configuration (all else being equal) is favored, has been suggested to explain why the Birch reduction forms only 1,4-hexadiene. How does this account for the observation that no 1,3-cyclohexadiene is obtained from a Birch reduction ... 

A better route is the one shown in Scheme 11. The benzene complex 104 forms readily in near quantitative yield upon heating Ru(III) chloride and 1,3-or 1,4-cyclohexadiene in EtOH. The introduction of the Cp ligand is by hali-de/Mcp exchange. The classic procedure to 105 required a stoichiometric quantity of thallium or silver [103], but a very recent, improved procedure shows that cyclopentadiene/K2C03/ abs. EtOH can be used successfully [104]. Although beyond the scope of this review, it is interesting to note that the much less electrophilic complexes [(arene)Ru(C5Me5)] [PFg] are accessible in a one-pot procedure from RuClj [105]. The sequence Birch reduction/complexa-... 

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. 

These reactions of electrophiles with alkene complexes to abstract a hydride from the saturated carbon adjoining the coordinated ir-system can create a sequence for the functionalization of dienes that are derived from the Birch reduction of arenes. A commonly used example of this reaction is the abstraction of a hydride from (cyclohexadiene)Fe(CO)3 (Equation 12.71) by trityl cation as described by Fischer. Such hydride abstractions have been shown to occur by initial electron transfer, followed by H transfer in some cases. ... 

If a 1,4-cyclohexadiene TM contains an electron-donating group (EDG), different strategies would be expected. If the electron-donating group is located on one of the C=C double bonds, the TM could have come from a Birch reduction or a Diels-Alder reaction. However, if the electron-donating group is in an allylic position, then a Diels-Alder disconnection that locates the EDG on the diene would be an appropriate retrosynthesis. 

The complexes of cyclic dienes, such as 1,3-cyclohexadienes, are precursors to / -cyclohexadienyltricarbonyliron salts, which have been applied in origanic synthesis (p. 303). 1,4-Cyclohexadienes, available from the Birch reduction of arenes, are converted into the 1,3-diene complexes. The isomerization occurs through a transient f/ -allyliron hydride (p. 363). 

Cyclohexadienes have most often been derived from cyclohexadienones [42-45]. They are also available by Birch reduction and by Diels-Alder addition followed by elimination [46, 47]. 

Fundamental to the development of dienyl iron tricarbonyl chemistry has been the availability of substituted cyclohexadiene precursors arising from the Birch reduction. In this process, a wide range of aromatic compounds are readily reduced to their corresponding unconjugated cyclohexa-1,4-dienes without further reduction to a cyclohexane. The reaction is typically performed by adding sodium to a liquid ammonia solution of the substrate in the presence of an added alcohol. 

Birch reductions of alkyl benzoates are not normally feasible due to the preference for Bouveault-Blanc-type reduction of the ester group. However, it has now been found that if one to two equivalents of water are added to the ammonia before addition of the metal, then good yields of cyclohexadiene-esters [e.g. (191) from ethyl benzoate] can be realised. It is known that Birch reductions of benzoic acids can be used to generate dianonic species (192). These have been found to undergo conjugate additions to methyl acrylate and... 

Thermal Complexation. Because 1,4-cyclohexadienes are readily available from the metal-aimnonia reduction (Birch reduction) of the corresponding aromatie eompounds, they have been extensively studied as substrates for direct 1,4-diene complexa-... 

In case of benzene, the potassium salt of its anion-radical can be separated as a precipitate after benzene reduction by potassium in the presence of low concentrations of 18-crown-6-ether. For benzene, the heavy-form content is greatest in the solution, not in the precipitate. It is in the solution where most of the nonreduced neutral molecules remain. Since the neutral molecules are inert toward protons, the anion-radicals combine with the protons to give dihydro derivatives (products of the Birch reaction). Therefore, it is possible to conduct the separation chemically. The easiest way is to protonate a mixture after the electron transfer, than to separate the aromatic compounds from the respective dihydroaromatics (cyclohexadiene, dihydronaphthalene, etc.) (Chang and Coombe 1971, Stevenson and Alegria 1976 Stevenson et al. 1986a, 1986c, 1988). 

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