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A novel protocol for a significantly improved, practical, and chemoselective ammonia-free Birch reduction mediated by bench-stable sodium dispersions and recoverable 15-crown-5 ether is reported. A broad range of aromatic and heteroaromatic compounds is reduced with excellent yields. [ABSTRACT FROM AUTHOR]

Conspectus As a result of the unique physical and electrical properties, graphene continues to attract the interest of a large segment of the scientific community. Since graphene does not occur naturally, the ability to exfoliate and isolate individual layers of graphene from graphite is an important and challenging process. The interlayer cohesive energy of graphite that results from van der Waals attractions has been determined experimentally to be 61 meV per carbon atom (61 meV/C atom). This requires the development of a method to overcome the strong attractive forces associated with graphite. The exfoliation process that we, and others, have investigated involves electron transfer into bulk graphite from intercalated lithium to yield lithium graphenide. The resulting graphenide can be reacted with various reagents to yield functionalized graphene. As a part of our interest in the functionalization of graphene, we have explored the Birch reduction as a route to hydrographenes. The addition of hydrogen transforms graphene into an insulator, leading to the prediction that important applications will emerge. This Account focuses mainly on the characterization of the hydrographenes that are obtained from different types of graphite including synthetic graphite powder, natural flake graphite, and annealed graphite powder. Analysis by solid state 13C NMR spectroscopy proved to be important since it was shown that the hydrographenes are composed of interior, isolated aromatic (predominantly fully substituted benzene) rings surrounded by saturated rings. The expected clusters of benzene rings were not found. NMR spectroscopy also offers strong evidence for the presence of tert-butyl alcohol and ethanol (workup solvent) that could not be removed in vacuo from the samples. These compounds could be observed to move freely within the layers of the hydrographene. High-resolution transmission electron microscopy images revealed a remarkable change in morphology that results when hydrogen is added to the graphenide. The appearance of edge and circular dislocations and increased distances between graphitic layers are most visible in the case of the hydrographenes that are formed from annealed graphite. The repetitive hydrogenation of synthetic graphite powder leads to an increase in the distances between the graphitic layers in the (002) direction from 3.4 Å for the initial graphite to 4.11 Å after the first reduction and to 4.29 Å after a third reduction of the same material. Defect-free graphite is formed when the hydrographenes are heated. The distance between carbon layers decreases from 4.11 to 3.44 Å after heating the samples to 1200 °C. This trend toward the spacing of graphite confirms the reversibility of the functionalization process. The C-H bonds have been broken yielding hydrogen, and the exposed carbon orbitals are in close enough proximity to have reverted to graphite. This Account introduces only a narrow area of materials chemistry, and many applications of graphene and its derivatives can be expected as researchers exploit this burgeoning field. [ABSTRACT FROM AUTHOR]

Single-layer graphene chemically reduced by the Birch process delaminates from a Si/SiOx substrate when exposed to an ethanol/water mixture, enabling transfer of chemically functionalized graphene to arbitrary substrates such as metals, dielectrics, and polymers. Unlike in previous reports, the graphene retains hydrogen, methyl, and aryl functional groups during the transfer process. This enables one to functionalize the receiving substrate with the properties of the chemically modified graphene (CMG). For instance, magnetic force microscopy shows that the previously reported magnetic properties of partially hydrogenated graphene remain after transfer. We also transfer hydrogenated graphene from its copper growth substrate to a Si/SiOx wafer and thermally dehydrogenate it to demonstrate a polymer- and etchant-free graphene transfer for potential use in transmission electron microscopy. Finally, we show that the Birch reduction facilitates delamination of CMG by weakening van der Waals forces between graphene and its substrate. [ABSTRACT FROM AUTHOR]

A library of star-shaped 2H-imidazolines has been synthesized via Debus-Radziszewski condensation from 1,2-diketones and ketone starting materials. Selective reduction of one imine group of the 2H-imidazole intermediate with LiAlH4 or catalytic flow hydrogenation furnished 2H-imidazolines, which could be conveniently diversified by reacting the amine N with electrophiles, resulting in a set of 21 amide-, carbamate-, urea-, and allylamine-containing products. In total, five points of diversification could be used, which allow the production of a set of functionally diverse compounds. The synthesis of acylated 2H-imidazolidines resulted in intrinsically labile compounds, which spontaneously degraded to acyclic derivatives, as shown for the reaction of 2H-imidazolidine with hexylisocyanate. [ABSTRACT FROM AUTHOR]

An efficient and operationally simple approach to complex cis-hexahydroindanes is reported. Upon Birch reduction of unprotected, C4-alkylated tetrahydroindanols and electrophiiic trapping of the tetrasubstituted enolate, as-fused products are formed with a new stereogenic quaternary carbon. The reaction is convergent, completely diastereoselective, and shows a broad scope with regard to the electrophile. [ABSTRACT FROM AUTHOR]

Birch reductive alkylation of methyl m-(hydroxymethyl)benzoate derivatives, using lithium in ammonia-tetrahydrofuran in the presence of tert-butyl alcohol, can be achieved without significant loss of benzylic oxygen substituents. Similar treatment of o- and p-(hydroxymethyl)benzoate derivatives results largely in loss of benzylic oxygen substituents. The results are rationalized by computations describing electron density patterns in the putative radical anion intermediate involved in these reactions. [ABSTRACT FROM AUTHOR]

The Birch reduction (lithium in liquid ammonia) of graphite gives a highly reduced, exfoliated product that is free of lithium. Edge and interior hydrogenation were demonstrated by solid-state 13C NMR spectroscopy. Elemental analysis of a carefully purified sample allows the chemical composition to be expressed as (C1.3H)n. Atomic force microscopy images showed that the reduced graphene was highly exfoliated. Hydrogen mapping by electron energy loss spectroscopy showed that the entire surface of the reduced sample was covered by hydrogen, consistent with the NMR studies also indicating that hydrogen was added in interior positions of the graphene lattice as well as along the edge. A large band gap (4 eV) further establishes the high level of hydrogenation. [ABSTRACT FROM AUTHOR]

The Birch Reduction is one of the main reactions of organic chemistry. The reaction involves the reaction of dissolving metals in ammonia with aromatic compounds to produce 1,4-cyclohexadienes. Discovered by Arthur Birch in 1944, the reaction occupies 300 pages in Organic Reactions to describe its synthetic versatility. Thus, it is remarkable that the reaction mechanism has been so very controversial and only relatively recently has been firmly established. Perhaps this is not that surprising, since the reaction also has many unusual and esoteric mechanistic facets. Here, I provide a description of how I have applied ever-evolving levels of quantum mechanics and a novel experimental test to understand details of the mechanism and the origins of the selectivities observed in the Birch reduction. The reaction involves an initial radical anion resulting from introduction of an electron from the blue liquid ammonia solution of free electrons formed by the dissolution of Li or related metals. This radical anion is protonated by an alcohol and then further reduced to a carbanion. Finally, the carbanion is protonated using a second proton to afford a nonconjugated cyclohexadiene. The regiochemistry depends on substituents present. With 18 resonance structures in the case of anisole radical anion, prediction of the initial protonation site would seem difficult. Nevertheless, computational methods from Hückel theory through modern density functional calculations do correctly predict the site of protonation. An esoteric test established this mechanism experimentally. The nature of the carbanion also is of mechanistic interest, and the preponderance of the resonance structure shown was revealed from Hückel calculations involving variable bond orders. For the trianion from benzoic acid, parallel questions about structure are apparent, and have been answered. Some mechanistic questions are answered experimentally and some by modern computations. Recently, our mechanistic understanding has led to a variety of synthetic applications. For example, the preparation of alkyl aromatics from benzoic acids makes use of the intermediates formed in these reactions. This Account provides an overview of both experimental techniques and theoretical methodology used to provide detailed mechanistic understanding of the Birch Reduction. [ABSTRACT FROM AUTHOR]

Covalent addition reactions turned out to b~ one of the most important functionalization techniques for a structural alteration of single walled carbon nanotube (SWCNT) scaffolds. During the last years, several reaction sequences based on an electrophilic interception of intermediately generated SWCNTn- carbanions, obtained via Birch reduction or by a nucleophiic addition of organometallic species, have been developed. Nevertheless, the scope and the variety of potential electrophiles is limited due to the harsh reaction conditions requested for a covalent attachment of the functional entities onto the SWCNT framework. Herein, we present a significant modification of the reductive alkylation/arylation sequence, the so-called Billups reaction, which extends the portfolio of electrophiles for covalent sidewall functionalization to carbonyl compounds-ketones, esters, and even carboxylic acid chlorides. Moreover, these carbonyl-based electrophiles can also be used as secondary functionalization reagents for anionic SWCNT intermediates, derived from a primary nucleophi~ic addition step. This directly leads to the generation of mixed functional SWCNT architectures, equipped with hydroxyl or carbornyl anchor groups, suitable for ongoing derivatization reactions. A correlated absorption and emission spectroscopic study elucidates the influence of the covalent sidewall functionalization degree onto the excitonic transition features of carbon nanotubes. The characterization of the different SWCNT adducts has been carried out by means of Raman, UV-vis/nIR, and fluorescenLe spectroscopy as well as by thermogravimetric analysis combined with mass spectrometry and X-ray photoelectron spectroscopy analysis. [ABSTRACT FROM AUTHOR]

The reaction of 1,2-diphenylbenzene with rubidium metal in THF yields extremely sensitive and pyrophoric [η5{ 1,2-diphenyl-2,5-cyclohexadienyl}rubidium]∞ (1). Compound 1 characterizes a possible intermediate in a Birch-type reaction and represents a very rare example of a fully characterized organorubidium complex as well as an open main-group metal pentadienide as part of a six-membered ring. In the solid state the rubidium atoms interact with the cyclohexadienyl moiety, whereas the coordination sphere of the soft cation is additionally stabilized exclusively by several metal π-arene interactions despite the presence of strongly coordinating donors. The bonding situation was elucidated by MP2/def2-TZVPP calculations including population analysis. [ABSTRACT FROM AUTHOR]

The Birch reduction of aromatic rings to cyclohexadiene compounds is widely used in chemical synthesis and requires solvated electrons, the most potent reductants known in organic chemistry. Benzoyl-coenzyme A (CoA) reductases (BCR) are key enzymes in the anaerobic bacterial degradation of aromatic compounds and catalyze an analogous reaction under physiological conditions. Class I BCRs are FeS enzymes and couple the reductive dearomatization of benzoyl-CoA to cyclohexa-1,5-diene-1-carboxyl-CoA (dienoyl-CoA) to a stoichiometric ATP hydrolysis. Here, we report on a tungsten-containing class II BCR from Geobacter metallireducens that catalyzed the fully reversible, ATP-independent dearomatization of benzoyl-CoA to dienoyl-CoA. BCR additionally catalyzed the disproportionation of dienoyl-CoA to benzoyl-CoA/monoenoyl-CoA and the four- and six-electron reduction of benzoyl-CoA in the presence of a reduced low-potential bridged 2,2′-bipyridyl redox dye. Reversible redox titration experiments in the presence of this redox dye revealed a midpoint potential of E0′= -622 mV for the benzoyl-CoA/dienoyl-CoA couple, which is far below the values of other known reversible substrate/product redox couples in enzymology. This work demonstrates the efficiency of reversible metalloenzyme catalysis, which in chemical synthesis can only be achieved under essentially irreversible conditions. [ABSTRACT FROM AUTHOR]

Diastereoselective Birch reduction—alkylation reactions of bicyclic β-alkoxy-α,β-unsaturated carbonyl compounds and tricyclic analogues were investigated. Although the relative configuration of the product was altered according to the structure of the starting material, stereoselectivity of the reaction could be accounted for by similar reaction pathways. The product from the tricyclic β-alkoxy-α,β-unsaturated carbonyl compound corresponded to the trichothecene skeleton. [ABSTRACT FROM AUTHOR]

Birch reductive alkylation of 2-aminobiphenyls affords access to highly functionalized polyenes that react through a Pd(II)-catalyzed oxidative amination cascade or through a double 1,4-addition process to provide the tetracyclic skeleton of indole alkaloids with up to four stereogenic centers created in a single-pot operation. [ABSTRACT FROM AUTHOR]

An indirect method for effecting radical carbocyclization onto aromatic rings is described. Cross-conjugated dienones such as 13, readily prepared by Birch reduction of aromatic tert-butyl esters, in situ alkylation, and oxidation (10→ 11→ 12→ 13), undergo radical cyclization; the products (14) are aromatized by silylation, Saegusa oxidation, and treatment with BiCl3·H2O. A noteworthy feature of this route is that it provides opportunities to attach an additional substituent to the original aromatic ring. [ABSTRACT FROM AUTHOR]

The reaction of an excess of 1,1-diaryl-2,2-dicyanoethylenes (1) with Sml2 is biphasic for olefin with at least one available para position. The first phase is completed in less than 0.5 s with the second phase extending over a few hundred seconds. This phase is second order with respect to the radical anion, which is formed in the dead-time of the mixing in the stopped flow spectrophotometer and is overall of -1 order in the initial concentration of Sml2. In this phase, a dimer is formed between two radical anions with the formation of a CC bond between a benzylic and a para position. The second phase is enhanced by proton donors and shows an H/D kinetic isotope effect with MeOH. Minute amounts of ethylene glycol accelerated the reaction to such an extent that the second phase is ‘absorbed’ into the first, rendering it rate determining. In this phase, the dianionic dimer disproportionates after protonation to furnish the neutral species and the anion, which after second protonation provides the reduced product. When the two para positions are occupied by substituents, the reaction takes place by the traditional Birch reduction sequence of electron-proton-electron-proton-transfer steps. It is shown that the detour mechanism, coupling followed by disproportionation, should be typical of olefin but not of carbonyl reduction. This difference stems from the dissimilarity in protonation rate on carbon and oxygen. [ABSTRACT FROM AUTHOR]

Quaternary stereocenters on a 2-cyclohexen-1-one ring are synthesized with good to excellent levels of enantioselectivity. The quaternary stereocenter is created through a new synthetic sequence involving three reactions: the enantioselective Birch reduction-allylation, enol ether hydrolysis, and the Cope rearrangement. To illustrate the ability of the sequence to enantioselectively generate complex structures, a variety of substrates are described. Notably, the sequence works for the enantioselective generation of vicinal quaternary-tertiary stereocenters, the generation of congested arylic quaternary stereocenters, and hydroxyalkyl substituted quaternary stereocenters. [ABSTRACT FROM AUTHOR]

For the first time various heteroaromatic compounds with bridgehead nitrogen, including indolizines, bispyrrolopyrimidines, pyrroloquinolines, pyrroloisoquinolines, and bispyrrolopyrazines, were selectively partially reduced under Birch reduction conditions. It was found that the double bond in the fused heterocycles which possesses the highest LUMO density can be selectively reduced under these conditions. Indolizine 6, containing an ester group at C-6, was reductively alkylated to give dihydroindolizines 8 and 9 possessing a quaternary carbon center in good yield. It was found that ambident substrate 12, under Birch reduction conditions, underwent smooth partial reduction to give 4,5-dihydroquinoline 14 as a sole product with no evidence of reduction of the side chain olefin. It was also shown that electron-rich pyrroloisoquinoline 15, which cannot be reduced via catalytic hydrogenation conditions, was efficiently transformed into its dihydrocounterpart 16 by using the Birch reduction protocol. Finally, it was shown that various fused diazines were smoothly and stereoselectively reduced under Birch reduction conditions to give trans-4,5-disubstituted dihydropyrimidines 30 and 32 in virtually quantitative yields. [ABSTRACT FROM AUTHOR]

Shows that the Birch reduction gives a complex mixture of C[sub 60]H[sub 36] isomers. Transfer hydrogenation method of Ruchardt; Isolation of the isomers by preparative high-pressure liquid chromatography; Determination of nuclear magnetic resonance spectroscopic properties; Comparison of experimental chemical shifts against those computed using density functional theory.

Examines the preparation and Birch reduction-alkylation of 3-substituted 2-methyl-2,3-dihydroisoindol-1-ones. Importance of isoindolinone derivatives as intermediates in organic synthesis; Occurrence of mythylation at benzylic position; Role of methyl substituent in the stereoselectivity of enolate methylation.

Examines the photochemistry of 3-Trimethylsilyl-2 and 5-cyclohexadienones. Preparation of 4-acetoxymethyl-4-alkyl-3-trimethylsilyl-2 through the Birch reduction-alkylation reaction; Photostability of bicyclohexinones; Effects of the trimethylsilyl and methoxy substituents on the photochemical reactivity.

Presents a study deriving schemes for hydroxybenzoyl-CoA reductase (HBCR) iron sulfur protein. Use of Nernst equation in rate laws; Results from coupling electrochemistry and steady-state kinetics; Similarity between the derived mechanism for HBCR and that of the Birch reduction.

Investigates the regioselectivity of the birch reduction. Use of a partially deuterated medium; birch reductions of anisole, 1,3-dimethoxybenzene, 3-methoxytoluene and 2-methoxynaphthalene; Validity of the isotope selectivity hypothesis; Reaction kinetics; Carbanion and radical anion protonation steps.

Presents a study on the asymmetric total synthesis of pheromone (+)-epianastrephin from chiral benzamide. Result of Birch reduction-alkylation of chiral benzamide; Discussion of tandem iodolactonization-radical reduction sequence; Utilization of substitution pattern for asymmetric synthesis of 1,2,6,6-tetrasubstituted 1,4-cyclohexadienes.

Presents an efficient preparation of 3,4-dihydro-4,5-dialkyl-2-benzopyran-1-ones. Discussion of selected Birch reduction-alkylation of title compound; Usefulness of procedure in complex carbocyclic framework construction; Utilization of procedure in diterpene synthesis.

The Birch reduction is a reaction commonly taught in the second-year undergraduate organic curriculum that involves the reduction of an aromatic compound to an alicyclic product using sodium metal and liquid ammonia. The experimental procedure can be challenging for novice chemists and thus has not been widely performed in introductory organic laboratories. An experimental procedure appropriate for introductory organic students is described that utilizes commercially available sodium-impregnated silica gel that is safer and easier to handle. This modified Birch reduction effectively reduces naphthalene to 1,4-dihydronaphthalene while minimizing safety concerns associated with the use of alkali metals and liquid ammonia. [ABSTRACT FROM AUTHOR]

Alkali metals in silica gel (the Na2K-SG(I) reagent) cleanly effect Birch reductions of substrates with at least two or more aromatic rings. The reaction conditions are alcohol-free, ammonia-free, and achieve excellent yields and high selectivities at room temperature. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the synthesis of enantioselective kinamycins. It mentions that the synthesis involves 12 linear steps from the Birch reduction of 3-(triiso-propylsilyloxy)-toluene. It explains the annulation strategy which allows the synthesis of substituted diazofluorenes in three steps from simple precursors such as α-oxidation, carbonyl reduction, and global deprotection.

The article presents a study which examines the mechanism of enzymatic Birch reduction and the stereochemistry and exchange reactions of benzoyl-CoA reductase (BCR). It addresses the unsuccessful studies in the stereochemistry of BCR reaction. It explores the stereochemistry of BCR reaction at the level of the 1,4-hydration product of dienoyl-CoA, 6-hydroxycyclohex-1-ene-1-carboxyl-CoA (6-OH-enoyl-CoA, 3), which is formed by the subsequent enzyme in the pathway, dienoyl-CoA hydratase (DCH).

Presents a high-yielding and versatile method for the reduction of electron deficient pyrroles to 3-pyrrolines. Selective manipulation and deprotection features; Application in organic compound preparation; Birch reduction of pyrroles and its derivatives.

A library of star-shaped 2H-imidazolines has been synthesized via Debus-Radziszewski condensation from 1,2-diketones and ketone starting materials. Selective reduction of one imine group of the 2H-imidazole intermediate with LiAlH4 or catalytic flow hydrogenation furnished 2H-imidazolines, which could be conveniently diversified by reacting the amine N with electrophiles, resulting in a set of 21 amide-, carbamate-, urea-, and allylamine-containing products. In total, five points of diversification could be used, which allow the production of a set of functionally diverse compounds. The synthesis of acylated 2H-imidazolidines resulted in intrinsically labile compounds, which spontaneously degraded to acyclic derivatives, as shown for the reaction of 2H-imidazolidine with hexylisocyanate.