Subject Birch reduction

The Birch reduction of a benzenoid compound involves the addition of two electrons and two protons to the ring. The order in which these additions occur has been the subject of both speculation and study. Several reviews of the subject are available and should be consulted for details. The present discussion is concerned with summarizing data that is relevant to understanding the reaction from the preparative point of view. For convenience, reaction intermediates are shown without indicating their solvation by liquid ammonia. This omission should not obscure the fact that such solvation is largely responsible for the occurrence of the Birch reduction. 

Reduction of a conjugated enone to a saturated ketone requires the addition of two electrons and two protons. As in the case of the Birch reduction of aromatic compounds, the exact order of these additions has been the subject of study and speculation. Barton proposed that two electrons add initially giving a dicarbanion of the structure (49) which then is protonated rapidly at the / -position by ammonia, forming the enolate salt (50) of the saturated ketone. Stork later suggested that the radical-anion (51), a one electron... 

Reduction of aromatic compounds to dihydro derivatives by dissolved metals in liquid ammonia (Birch reduction) is one of the fundamental reactions in organic chemistry308. When benzene derivatives are subjected to this reduction, cyclohexa-1,4-dienes are formed. The 1,4-dienes obtained from the reduction isomerize to more useful 1,3-dienes under protic conditions. A number of syntheses of natural products have been devised where the Birch reduction of a benzenoid compound to a cyclohex-1,3-diene and converting this intermediate in Diels-Alder fasion to polycyclic products is involved (equation 186)308f h. 

Polyfullerenes C qH with n reaching from 18 to 44 were observed imder Birch conditions (for n > 44 see Section 5.3.4). Isomers with more than 36 hydrogens could not be obtained with the usual Birch procedure. Much milder conditions were necessary and were found with the Benkeser reduction [43]. CgoHjg, obtained with Birch reduction, was subjected to a reduction with li in refluxing ethylene-diamine and yielded four new polyhydrofullerenes, C qH with n = 38, 40, 42 and 44 [43]. These derivatives could be separated by preparative HPLC and characterized by mass spectrometry. 

This type of Birch reduction-alkylation also works in the naphthalene series36. Thus, the naphthalene carboxamides 10. when subjected to the standard Birch reduction-alkylation conditions, furnish a single set of diastereomers 11 (d.r. >95 5 by ]II and 13C NMR no experimental details given)36. 

The synthesis of prostaglandin PGB1 as described by Morin et al. (Eli Lily Research Labs.), starts with 7-(2-methoxyphenyl)heptanoic acid 142 which is converted into 143 through Birch reduction, esterification and acetalization. Ozone cleavage of 143 and cyclization of the resulting dialdehyde affords cyclopentene carbaldehyde 144 which was subjected to ( )-selective Wittig olefination with... 

Most of the parent centropolyindanes have been subjected to partial reduction of the benzo rings [133, 134]. Birch reduction of fenestrindane 9, for example, leads to the [5.5.5.5]fenestratetraene 272 bearing four annelated 1,4-... 

The isoquinoline (251) was subjected to the Dryden modification of the Birch reduction (73) to afford the enol ether (252), which was treated with hot phosphoric acid to give tetrahydrohomoglaziovine... 

TTHE REACTION OF benzene or one of its derivatives with an alkali metal in liquid ammonia containing an alcohol cosolvent is known as the Birch reduction (1-6). As expected with anionic intermediates, 1-substituted-1,4-dihydro products result from electron-withdrawing groups, and 2,5-dihydro products result from electron-donating groups, as shown in Scheme I. Application of these conditions to polynuclear aromatic compounds produces complications because the products formed initially are subject to reduction under the reaction conditions (3). Although methods such as the use of iron salts minimize side reactions, more recently developed procedures avoid... 

The reactions for the conversion of the AMformyl derivative (253) to chasmanine were studied (160) in a model system starting with compound 277. Birch reduction of 277 afforded compound 278, which was subjected to equilibration in methanolic hydrochloric acid-dioxane under reflux for six days to give epimers 278 and 279 in a ratio of 2.7 1. These epimers were separated by careful column chromatography on silica gel. The... 

New and continuing efforts towards the total synthesis of dendrobine (59 R = H) have been reported.In one sequence (Scheme 8), the butyric acid (85) was readily transformed into the ketal (86), which was submitted to a Birch reduction and hydrolysis to yield the cyclohexenone (87) as the single diastereomeric product. Acid treatment of (87) gave a stereoisomeric mixture of products (88) which were not separated but subjected to reaction with base to give compound (89). The same compound was obtained directly by treatment of (87) with strong base (Michael and aldol condensations combined). After some discouraging results, the tricyclic compound (89) was transformed into the desired keto-acid (90) via an abnormal ozonolysis reaction. Compound (90) possesses the correct stereochemistry at three asymmetric centres required for elaboration of dendrobine (59 R = H). 

A new synthesis of N-formylnordihydrothebainone, and hence a formal synthesis of codeine and morphine, has been reported. The (+)-(R)-isomerof the tetrahydroisoquinoline (156) was subjected to Birch reduction, iV-formylation, and cyclization (with scission of the benzyl ether groups) to give N-formyl-2-hydroxynordihydrothebainone (157). Selective conversion of this into the 2-(l-... 

The stereoselectivity of the reaction was determined by converting both p-lactams 204 and 205 into the corresponding hydroxy compounds 206 and 207, followed by removal of the chiral auxiliary under Birch reduction conditions and further benzoylation. The resulting P-lactams 208 and 209 were subjected to HPLC analysis indicating that the ratio of cis and trans isomers was 95 5 for both compounds. After purification by column chromatography the optical purity of the major isomer was found to be 70% ee. 

Lithiated allyl sulfide 256-Li reacted with m-xylylene dibromide 257 to afford the bis-sulfide 258. A double Mislow-Evans rearrangement of 258 and subsequent reductive trapping of the sulfenate ester provided the symmetric trans-diol 255. Monoprotection, Sharpless asymmetric epoxidation, and reductive ring-opening of the epoxide gave 1,3-diol 259 in 97% ee. After several functionalizations, the arene was subjected to Birch reduction to provide 1,4-cyclohexadiene 254. Ozonolysis of the diene, followed by reductive workup and treatment of the resulting 1,3-diketone with acid furnished pyra-... 

Birch reduction is a standard reductive procedure of aromatic molecules to non-aromatic derivatives. Similar to the two-electron oxidation of phenol derivatives to the corresponding dienones, the Birch protocol is considered to involve reductive conversion of aromatic compounds to cyclohexadienes. When aromatic compounds were subjected to cathodic reduction in the presence of a proton source, Birch-type reduction products were produced (Scheme 5) [20 - 22]. 

In this chapter, an overview of dearomatization tactics employed in organic synthesis is presented. The material is organized according to mechanistic considerations and includes discussion of conventional as well as transition metal-mediated dearomatization reactions, with particular emphasis accorded to asymmetric processes. This chapter highlights the most common dearomatization reactions encountered in synthesis (with the exclusion of the Birch reduction—the topic of another chapter in this volume) and is not meant to provide a comprehensive treatise on the subject. Only dearomatization reactions of carbocyclic arenes are discussed. 

Birch reduction of 2-acyl- or 2-acetyl-5-alkylthiophenes and subsequent alkylation with an aUcyl halide gave 2-acyl-2-alkyl- or 2-acyl-2,5-dialkyl-2,5-dihydrothiophenes in moderate to good yields. As illustrated in Scheme 123, for a series of substrates, both 2-acylthiophenes and thiophene-2-carboxylic acid were tolerated in this process. The compounds 123 represent useful synthetic intermediates, which can be further converted into 1,3-dienes. Substituted dihydrothiophenes were subjected to m-CPBA, followed by thermolysis, and finally provided a series of 1,3-dienyl ketones [141]. 

When thien-2-ylacetic acid was subjected to the abovementioned reaction coti-ditions, similar ring opening was observed and the products consisted of (Z)-3-benzylthio-3-hexenoic acid and (Z)- and ( )-3-benzylthio-2-hexenoic acid with the ratio of 84 12 4. As illustrated in Scheme 127, the Birch reduction of 2-(thien-2-yl) propanoic acid with five equivalents of sodium in liquid ammonia in the presence of ethanol and a subsequent treatment with ammonium chloride and benzyl bromide led to the formation of (Z)-3-benzylthio-2-methyl-3-hexenoic acid in the yield of 63%. Additionally, under similar reaction conditions, 2-(thien-2-yl)hexenoic acid and 2-(thien-2-yl)-4-pentenoic acid also created the corresponding (Z)-3-benzylthio-2-butyl-3-hexenoic acid and (Z)-2-allyl-3-benzylthio-3-hexenoic acid with 77 and 76% yields, respectively [140]. 

The first synthesis and AC determination of a 3-fame-sene-trimethoxystyrene conjugate (R)-(- -)-140 were accomplished. A synthetic precursor ( )-138 was enantioresolved as MaNP ester by HPLC, and their ACs were determined by H NMR anisotropy. The second-eluted ester (5 15, 55)-( )-139b was subjected to the Birch reduction giving the target compound (R)-(+)-140. ... 

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