Birch reduction 1,3-cyclohexadiene

Birch reduction (Section 11 11) Reduction of an aromatic nng to a 1 4 cyclohexadiene on treatment with a group I metal (Li Na K) and an alcohol in liquid ammonia Boat conformation (Section 3 7) An unstable conformation of cyclohexane depicted as... 

With an effective strategy for construction of the diazofluorene established, we set out to prepare the coupling partners required for synthesis of (—)-kinamycin F (6). The synthesis of the enone 117 began with meta-cresol (128, Scheme 3.23). Silylation formed the silyl ether 119 in nearly quantitative yield. Birch reduction of the silyl ether 119 formed the cyclohexadiene derivative 129 in excellent yield. Asymmetric dihydroxylation [52] of 129 occurred regioselectively to afford the... 

Silylated 1,4-cyclohexadienes, such as 58, are accessible by the Birch reduction of resorcin dimethyl ether and subsequent one-pot silylation-methylation. The reduction of bromo adamantane with 58, occurs readily in the presence of the radical initiator AIBN, with the driving force being the aromatization leading to 59 (Scheme 14). 

A solution of lithium, sodium, potassium or calcium in liquid ammonia can reduce a wide variety of unsaturated groups. Thus when aromatic rings are reduced by such metals in liquid ammonia, non-conjugated cyclohexadienes are produced. The reaction is called Birch reduction. 

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. °... 

Birch reduction of enantiomcrieally pure benzamides followed by alkylation of the amide enolate was used with remarkable success to obtain chiral cyclohexadiene derivatives22. In this case the chiral auxiliary was located in the benzamide moiety. 

The combined Birch reduction alkylation of chiral, enantiomerically pure aroyl amides of 2-pyrrolidinemethanol (prolinol) or 2-pyrrolidinecarboxylic acid (proline) gives chiral, non-racemic, 1,1-disubstituted 2,5-cyclohexadienes 1 or 2-cyclohexenes 2, respectively, in high diastereomeric ratios. These reactions are useful for the preparation of valuable chiral synthetic intermediates 3 25 29-31-36. 

Table6. 1,1-Dialkylated 2,5-Cyclohexadienes by Birch Reduction-Alkylation of l-Aroyl-2-pyrrolidinemethanol Derivatives32 3, 38,3y 1. k/nh3/thf...

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. 

Problem 10.22 In the Birch reduction benzene is reduced with an active metal (Na or Li) in alcohol and liquid NHj(-33 °C) to a cyclohexadiene that gives only OCHCH CHO on ozonolysis. What is the reduction product ... 

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... 

Recently, two completely different methods which are compatible with an alkene have been used successfully. The first of these involves121 prior Birch reduction of the phenyl group to a cyclohexadiene. Subsequent treatment with fluoride ion and basic hydrogen peroxide then completes the overall cleavage (equation 31). 

Reduction of substituted benzenes with sodium (or lithium) in liquid ammonia in the presence of a proton source (such as methanol, ethanol, etc.) leads to a substituted, non-conjugated cyclohexadiene as a result of 1,4-addition of hydrogen (the Birch reduction).16 With benzene the product is cyclohexa-1,4-diene as a result of the following mechanistic pathway. 

Birch reductions of monosubstituted arenes yield 1,4-cyclohexadiene derivatives in which the alkyl group is a substituent on the double bond. With p-xylene, both methyl groups are double-bond substituents in the product. 

Cyclohexadienes are avaiable by the Birch reduction of aromatic compounds, and converted to 1,3-diene complexes by heating with Fe(CO)5. l-Methoxy-1,4-... 

The Birch Reduction offers access to substituted 1,4-cyclohexadienes. 

Catalytic hydrogenolysis using Pd—C, Pd(OH)2 or Pd(OAc)2 is the most commonly employed method for the removal of benzyl ethers, and yields are often quantitative. Cyclohexene, cyclohexadiene, formic acid and ammonium formate can also be used as hydrogen sources rather than hydrogen. Benzyl ethers can also be removed by Birch reduction with lithium or sodium dissolved in liquid ammonia, but this procedure is not often applied in carbohydrate chemistry. 

The product of a Birch reduction is 1,4-cyclohexadiene. Offer a reason why this product is not further reduced under the reaction conditions. 

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... 

Alkali metals in liquid ammonia in the presence of an alcohol reduce aromatic systems to 1,4-cyclohexadienes. These can be further elaborated into a host of derivatives. The availability of a wide variety of substituted aromatic compounds, either commercial or via synthesis, makes the Birch reduction an important tool in organic synthesis. 

Regiochemistry. Birch reduction of monosubstituted benzenes could furnish either of two possible 1,4-cyclohexadienes, A or B below. 

In the laboratory of A.G. Schultz during the asymmetric total synthesis of two vincane type alkaloids, (+)-apovincamine and (+)-vincamine, it was necessary to construct a crucial c/s-fused pentacyclic diene intermediate. The synthesis began by the Birch reduction-alkylation of a chiral benzamide to give 6-ethyl-1-methoxy-4-methyl-1,4-cyclohexadiene in a >100 1 diastereomeric purity. This cyclohexadiene was first converted to an enantiopure butyrolactone which after several steps was converted to (+)-apovincamine. 

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