Birch reduction with

The first part is a Birch reduction, with NH3 as the proton source. It gives the carboxylate enolate as the initial product. When the alkyl halide is added, the enolate acts as a nucleophile to give the C3-C7 bond in an Sn2 reaction. 

The superfluous bromine is then removed by reduction with zinc in acetic acid (26-1). The 20 ketone is next protected against the strongly reducing conditions in the subsequent step by conversion to the ethylene glycol acetal (26-2). Birch reduction with lithium in liquid ammonia in the presence of ethanol proceeds as usual to the dihydrobenzene (26-3). Treatment of this last product with mineral acid serves to hydrolyze both the enol ether at the 3 position and the acetal at the... 

The two free hydroxy groups are First protected with acetic anhydride. In a second step the acetyl group is reductively cleaved by a Birch reduction with lithium in liquid ammonia.19 Lithium dissolves in the ammonia with the formation of solvated electrons. Stepwise electron transfer to the aromatic species (a SET process) leads first to a radical anion, which stabilizes itself as benzylic radical 38 with loss of the oxygen substituent. A second SET process generates a benzylic anion, which is neutralized with ammonium chloride acting as a proton source (see Chapter 12). 

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 use of 1,1-diiodomethane as an electrophile in the Birch reduction (with lithium in liquid ammonia) of electron-deficient pyrroles 915 furnished pyrrolines 916 (in high to excellent yields), which provided access to the synthetically important functionalized 5,6-dihydro-2(l//)-pyridinones 917 (via radical ring expansion), substructures commonly found in biologically active natural products (Scheme 177) <2004CC1422>. 2-(Chloroalkyl)-substituted pyrrolines 919 were duly prepared by the reductive alkylation (with l-chloro-3-iodopropane or 1-chloro -iodobu-tane) of electron-deficient pyrrole 918. Allylic oxidation then furnished lactams 920 (Scheme 178). 

An interesting alternative to the Birch reduction with useful synthetic potential is provided by reductive silylation. Benzene, on treatment with lithium metal and trimethylsilyl chloride in THF for a pro-... 

Although one successful synthesis of equilin from equilenin methyl ether has been reported, Birch reductions of such substrates are non-selective, since reduction of both aromatic rings occurs. Use of the free phenol in such reductions, however, has neatly overcome these difficulties. Formation of the naphthoxide ion prior to Birch reduction with lithium-ammonia at — 70 °C has resulted in high yields of equilin. Surprisingly, further reduction of equilin 17-dimethylketal... 

The Birch reduction with alkali metals in liquid ammonia has been described for Cso already in 1990, just shortly after its isolation. A mixture of highly hydrogenated fullerene compounds QqHj, (18 < x < 36) is generated especially with lithium in ammonia in the presence of tert-butanol. Again C >Hi8 and CgoHsg are the major products. Derivatives with even more hydrogen attached carmot be obtained by Birch reduction as they decompose at the conditions applied. 

The preeminence of lithium and sodium in metal reductions has been challenged by the use of calcium in amines, developed by Benkeser. In the initial work, naphthalene was reduced to an 80 20 mixture of A -octalin (522) and A ( )-octalin (523) with lithium in diethylamine-dimethylamine. Replacing lithium with calcium gave a 77 23 mixture of 522 and 523 in 92% yield. This method has come to be called the Benkeser reduction. This has become an important modification because Birch reductions with sodium are... 

Reductive alkylation of a-tetralones, a-Tetralone (1) has been converted into 2 in 607 yield by Birch reduction with potassium and r-butyl alcohol in liquid ammonia at —78° followed by addition of lithium bromide and then methyl iodide. Australian chemists have found that this reductive alkylation is gener-... 

The Eschenmoser-Claisen rearrangement has found numerous applications in the synthesis of terpenoids and steroids. A recent example is Loh s formal synthesis of deoxyanisatin (Scheme 7.29, Eq. 1) [63]. Treatment of 79, the product of a Birch reduction, with DMADMA gave amide 80 after migration of a double bond. Other versions of the Claisen rearrangement lead only to decomposition or re-aromatization. The aUylic quaternary stereocenter of dysidiolide was installed through rearrangement of aUytic alcohol 81 to afford octahydronaphtalene 82... 

The catalytic hydrogenation of the cis-A/B ketone (151) gave the cis-syn-c is-isomer (152). The Birch reduction of the ketone (151) via the corresponding ethylene ketal led after hydrolysis to a mixture of the cis-anti-trans-isomer (154) and the cis-syn-trans-isomer (155) in a ratio of 2 1. The stereodirected synthesis of the isomer (154) was effected from the 3q -hydroxy derivative (153) by Birch reduction with subsequent oxidation of the 3ce-hydroxy group. 

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