Lithium In Liquid Ammonia Research Articles

Reductive cleavage of 1-methyltricyclo[4.4.0.0 2,6]Decan-3-one and related compounds with lithium in liquid ammonia

Reductive cleavage of 1-methyltricyclo[4.4.0.0 2,6]Decan-3-one and related compounds with lithium in liquid ammonia

ChemInform Abstract: CYCLOPENTANONES. XVIII. THE LITHIUM‐LIQUID AMMONIA REDUCTION OF SOME 2,3‐DIALKYL‐4‐HYDROXY‐2‐CYCLOPENTENONES. THE IMPORTANCE OF THE PROTONATION OF INTERMEDIATE ENOLATE ANIONS ON THE STEREOCHEMICAL OUTCOME

AbstractDie Stereochemie der Reduktion der Cyclopentenone (I) und der Hydroxy‐cyclopentenone (IV) in Gegenwart verschiedener Protonendonatoren (Phenol, Methanol, Äthanol, Isopropanol, tert.‐Butanol) wird untersucht.

Cyclopentanones—XVIII : The lithium-liquid ammonia reduction of some 2,3-dialkyl-(4-hydroxy)-2-cyclopentenones. the importance of the protonation of intermediate enolate anions on the stereochemical outcome

The stereochemical outcome of the lithium-liquid ammonia reduction of 2,3-dialkyl-4-hydroxy-2-cyclopentenones and 2,3-dialkyl-2-cyclopentenones possessing bulky substituents (i-propyl and t-butyl) is investigated, using different proton donors. The relative configuration of both alkyl groups in the reduction products is interpreted on the basis of the geometry of the transition state for protonation of the intermediate enolate anions formed during the reduction

ChemInform Abstract: CYCLOPENTANONES. XVII‐ PROSTAGLANDIN SYNTHESIS INVOLVING THE LITHIUM‐LIQUID AMMONIA REDUCTION OF 3‐ALKYL‐4‐HYDROXY‐2‐(1′‐OCTYNYL)‐2‐CYCLOPENTENONES

AbstractLi/NaH‐Reduktion des Cyclopentenons (Ia) in Gegenwart von Na‐äthylat liefert als Hauptprodukt das Desoxy‐8‐epi‐PGF,a (IIa), während bei der Reduktion von (Ia) in Gegenwart von Phenol hauptsächlich das Desoxy‐PGFlß (IIIa) (geringe Ausbeute) entsteht; neben (IIa) bzw. (IIIa) werden jeweils die entsprechenden Isomeren (IIIa) bzw. (IIa), verschiedene weitere Isomere sowie gesättigte Verbindungen gebildet.

ChemInform Abstract: CLEAVAGE OF DIMETHYL SULFOXIDE BY ALKALI METALS

AbstractDie reduktive Spaltung von DMSO (I) durch zwei Äquivalente Li in flüssigem Ammoniak in Gegenwart von tert.‐Butanol liefert Methansulfenat (II) als Li‐Salz, das durch Einwirkung von Alkylbromiden zu den Sulfoxiden (III) reagiert.

Mannich reaction in a number of six-membered heterocyclic ?,-ketones. X. Stereochemistry of the reduction and phenylation of 2, 2-dimethyl-5-dimethylaminomethyl-4-oxotetrahydropyran

2, 2-Dimethyl-5-dimethylaminomethyl-4-oxotetrahydropyran was subjected to reduction with lithium aluminum hydride, sodium borohydride, aluminum isopropoxide, and lithium in liquid ammonia, to catalytic hydrogenation over Raney nickel, and phenylation with phenyllithium. The quantitative ratios in the resulting mixtures of stereoisomeric 2, 2-dimethyl-5-dimethylaminomethyl-4-hydroxytetrahydropyrans and their dependence on the character of the reducing agents were established by means of gas — liquid chromatography and PMR spectroscopy. The individual geometrical isomers of the amino alcohols were isolated, and their three-dimensional structures were studied by means of their PMR and IR spectra.

Cleavage of dimethyl sulfoxide by alkali metals

AbstractReaction of dimethyl sulfoxide with two equivalents of lithium in liquid ammonia gives a solution of lithium methanesulfenate which can be alkylated or benzylated to yield the corresponding sulfoxide.

Studies on 1-azabicyclo compounds. XXV. Synthesis of nine-membered ring aminolactams and related compounds from octahydropyrrolo(1,2-alpha)pyrazin-1-one (author's transl)

Reduction of both methiodides, II and XI, with lithium in liquid ammonia or sodium amalgam gave nine-membered aminolactams, III and XII, respectively, which, on treatment with lithium aluminum hydride, afforded the correspouding diamines, IV and XIII. Diamines (IV and XIII) were also obtained by lithium aluminum hydride reduction of II and XI, respectively. Reduction of XV with lithium in liquid ammonia yielded XVI.

The total synthesis and anti-fertility activity of 6-silasteroids

4,4-Dimethyl-6-methoxy-4-sila-1-tetralone ( 2) was prepared by a modified literature procedure and converted to 3-methoxy-6,6-dimethyl-6-silaestra-1,3,5(10),8,14-pentaen-17β-yl acetate ( 5c). Catalytic hydrogenation of 5c gave 3-methoxy-6,6-dimethyl-6-silaestra-1,3,5(10),8-tetraen-17β-yl acetate ( 6b), and its 14-iso- and Δ 1,3,5(10),8(14) isomers, the proportions varying with the catalyst and solvent. Reduction of 6b with lithium-liquid ammonia, and O-demethylation, gave 6,6-dimethyl-6-silaestradiol ( 8b). Reduction of the 3-methyl ether of 8b with lithium-liquid ammonia- t-butanol and hydrolysis afforded 3-keto-6,6-dimethyl-6-silaestr-1(10)-en-17β-ol ( 15), which was catalytically reduced to its 1,10α-dihydro derivative 17. The 5,6 SiC bond of 8b, 15 and their derivatives was cleaved by boron tribromide, aq. ethanolic hydrogen fluoride, and other reagents, providing a series of 5,6-seco-6,6-dimethyl-6-silasteroids. X-ray crystallographic analysis of 17 and the 17α-ethynyl derivative of 15 confirmed the stereochemical assignments. None of the compounds which were subjected to uterotropic, anti-uterotropic, or post-coital assays, showed significant activity. A partially completed synthesis of 6-silaestradiol ( 21a) is described.

Studies on 1-azabicyclo compounds. XXVI. Synthesis of ten-membered ring amines from 9a-cyanomethyl-, 9a-ethoxycarbonylmethyl-, and 1-ethoxycarbonyl-octahydroquinolizine.

Quaternization of 9a-cyanomethyl- and 9a-ethoxycarbonylmethyl-octahydroquinolizine (VI and XI) with methyl iodide afforded cis (VIIa and XIIa) and trans methiodides (VIIb and XIIb), respectively. On treatment with lithium in liquid ammonia, the methiodides (VIIa, XIIa, and XXIV) gave the ten-membered ring amines (VIII, XIII, and XXV), respectively, in moderate yields, however, the methiodide (XXIX) gave only the demethylated product (XXVIII). And the methiodide (VIIa) yielded also the decyanated amines (IX and X) as the by-products. The formation of the ten-membered ring amines (VIII, XIII, and XXV) was proved to proceed as shown in Chart 5 via the unsaturated ten-membered ring amines (XVII, XVIII, and XXX), which were actually derived from the methiodides (VIIa, XIIa, and XXIV), respectively. On the other hand, treatment of VIIa and XIIa with sodium ethoxide afforded the endocyclic olefinic ring amines (XV and XVI), which were shown to be obtained by isomerization of the initially formed exocyclic olefinic ring amines (XVII and XVIII), respectively.

The synthesis of Tetracyclo[5,3,1,03,5,04,9]undecan-2-one and the acid-catalysed and reductive cleavages of the cyclopropyl ring

Tetracyclo[5,3,1,03,5,04,9]undecan-2-one (2,4-dehydro-5-homoadamantanone) (3) was synthesized by copper-catalysed intramolecular insertion of a diazoketone into a double bond. Acid-catalysed opening of the cyclopropyl ring in aqueous acetic acid cleaved the C3-C4 bond to give a mixture of exo-7-hydroxytricyclo[4,3,1,13,8]undecan-4-one (13) and its acetate (12). Under the same conditions except for the presence of bromide ion, a mixture of (12), (13) and exo-7- bromotricyclo[4,3,1,13,8]-undecan-4-one (17) was obtained. Reduction of (17) with LiAlH4 gave homoadamantanol. Reduction of (3) with lithium in liquid ammonia gave cleavage of the C 3-C 5 bond to afford tricyclo[5,3,1,04,9]-undecan-2-one (4), the structure of which was confirmed by independent synthesis.

Cyclopentanones—XIII: The proton donor depending stereoselectivity of lithium ammonia reduction of 2,3-dimethyl-4-hydroxy-2-cyclopentenone

The stereochemistry of the lithium-liquid ammonia reduction of 2,3-dimethyl-4-hydroxy-2-cyclopentenone is discussed as a function of the acidity of the proton donor. It is shown that the configuration of the resulting 2,3-dimethyl-1,4-dihydroxycyclopentene is determined by competing intra- and intermolecular protonation.

Cleavage of 1,4-diketones on reduction with lithium in liquid ammonia. Conversion of cyclohexenone photodimers into the dihydrodimers

A mechanism is discussed for cleavage of the central carbon–carbon bond in 1,4-diketones, (CO)C–C(CO), when this bond is orthogonal to the planes of the two carbonyl functions; lithium–ammonia–t-butyl alcohol reduction of the 1,4-diketonic photochemical dimers from isophorone and cyclohexenone gave in each case one stereoisomer of the corresponding dihydrodimers.

Studies on 1-Azabicyclo Compounds. XVIII. Synthesis of Fourteenmembered Ring Diamine, 1, 8-Dimethyl-1, 8-diazacyclotetradecane, and Related Compounds from Perhydrodipyrido [1, 2-a : 1', 2'-d]-pyrazine via Ten-membered Ring Diamine, 2-Methyl-perhydro-2H-pyrido [2, 1-c]-2, 9-diazecine

Oxidation of the anti- and syn-diamine (IX and X) with mercuric acetate gave the enaminolactam (XII). Treatment of the methiodides (XIII, XVIII, and XIX) with lithium in liquid ammonia afforded the ten-membered ring aminolactam (XX) in an excellent yield, which was reduced to the ten-membered ring diamine (XXI). Hofmann degradation of the carbamate (XXIII) derived from XXI provided the fourteen-membered ring aminocarbamate (XXVII) and the oxazolidone (XXVIII), which were converted to the fourteen-membered ring diamine (XXX) and the hydroxydiamine (XXXI), respectively.

Stereoselectivity in the reductive cleavage of vinylcyclopropane

Treatment of vinylcyclopropane ( 6) with lithium in liquid ammonia at 0° or 25° slowly effects reductive cleavage to afford a mixture of cis-2-pentene ( 7), trans-2-pentene ( 8), and 1-pentene ( 9). The major product is 7 and the ratio 7:8 is greater at 0° (4·25) than at 25° (3·2). Control experiments have established that the products are stable in lithium amide-liquid ammonia at 25°. In contrast, product ratios for cleavage of 6 with sodium in liquid ammonia at 0° or 25° are somewhat variable due to equilibration under the reaction conditions, and 8 is the major product at longer reaction times at 25°. It is suggested that the predominant cis-stereoselectivity is greatest in solvent-separated ion pair transition states.

Synthetic plant growth regulators. II. The preparation of tricyclic helminthosporic acid analogues with gibberellin-like properties

Cyclopropyl ketone (13), prepared by the copper-catalysed decomposition of diazoketone (12), underwent specific cyclopropyl bond fission on reduction with lithium in liquid ammonia. Oxidation of the reaction product mixture followed by catalytic hydrogenation gave ketone (7) whose stereo-chemistry was established by degradation to trans-decalyl- 9-acetic acid (18), an authentic sample of which was prepared from trans-decalin-9-carboxylic acid. Ketone (7) was converted via its methylene derivative (21) to the pyrrolidinium salt (24) which underwent base induced [2,3]sigmatropic rearrangement, followed by hydrolysis, to give aldehyde (26). Acid (5) was formed by simple oxidation and converted by base catalysed isomerization of its methyl ester, then hydrolysis, into acid (6).

Cyclopentanones—VIII : Stereochemistry of the lithium-liquid ammonia reduction of 2,3-dialkyl-4-hydroxy-2-cyclopentenones

2,3-Dialkyl-1,4-cyclopentanediols are obtained by lithium-liquidammonia-alcohol reduction of 2,3-dialkyl-4-hydroxy-2-cyclopentenones. The configuration of the diastereoisomers formed was proved by 1H-NMR spectroscopy and by chemical evidence. In the most abundant isomer the alkyl groups are trans and each is in trans position to the vicinal hydroxyl function. In another diastereoisomer formed in substantial amount the alkyl groups have a cis orientation and are trans to the vicinal hydroxyl function. The 1H-NMR parameters found are more useful generally for configurational assignments to synthetic and modified prostaglandins.

Dimethylallylation products of phloroacetophenone; a convenient one-stage synthesis of deoxyhumulones

The structures of seven products of the reaction between 2-methylbut-3-en-2-ol and phloroacetophenone, catalysed by boron trifluoride–ether complex, are described; they include the important 2,4,6-trihydroxy-3,5-bis-(3-methylbut-2-enyl)acetophenone (4-deoxyacetohumulone). By a similar reaction the natural hop compounds 4-deoxyhumulone, 4-deoxycohumulone, and 4-deoxyadhumulone are readily synthesised. No 4-deoxyacetohumulone was obtained by reaction of 6-acetyl-2,2,8,8-tetramethyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-5-ol with lithium in liquid ammonia.

Studies on 1-Azabicyclo Compounds. XV. Oxidation of 1, 3, 4, 6, 11, 11a-Hexahydro-2H-pyrazino [1, 2-b] isoquinolin-1-one Derivatives with Mercuric Acetate, and Their Conversion into 1, 2, 3, 4, 5, 6, 7, 8-Octahydro-2-methyl-2, 5-benzodiazecine and Related Compounds

Oxidation of hexahydro-2H-pyrazino [1, 2-b] isoquinolin-1-one (Ia) with mercuric acetate gave the α-aminocarbinol (II), which was characterized as the quaternary ammonium bromide (III). Mercuric acetate oxidation of the diamine (VII), however, afforded the lactam (VIII). Treatment of the methiodides (XIIa, XIIb, and XIIc) with lithium in liquid ammonia yielded the piperazinones (XIIIa, XIIIb, and XIIIc), respectively. On the other hand, reduction of the methiodides (XIIa, XIIb, and XIIc) with sodium amalgam furnished selectively the ten-membered aminolactams (XVIa, XVIb, and XVIc), respectively, in fair yields, which were converted to the corresponding ten-membered diamines (XVIIa, XVIIb, and XVIIc).

Studies on 1-Azabicyclo Compounds. XIV. Synthesis of 1-Methyldecahydro-1, 4-diazecin-5-one from Octahydropyrido [1, 2-a] pyrazine Derivatives

Octahydropyrido [1, 2-a] pyrazine (VI) and its N-benzyl derivative (I) were subjected to oxidation by mercuric acetate to afford 1, 3, 4, 6, 7, 8-hexahydro-2H-pyrido [1, 2-a] pyrazin-1-one (VII) and its N-benzyl compound (II), respectively. The former product (VII) was also obtained by similar oxidation of the lactam (V). Compound (V) was treated with methyl iodide in methanol to give two isomeric methiodides, trans-octahydropyrido [1, 2-a]-pyrazin-1-one methiodide (Xa) and the corresponding cis-methiodide (Xb). On thermal treatment, the latter methiodide was converted into the former. Methiodides, IV, XI, Xa, and Xb were reduced with lithium-liquid ammonia giving the 10-membered ring lactam (XII) in 4%, 52%, 81%, and 82% yields, respectively. When treated with sodium amalgam, Xa gave XII in 59% yield, which, on reduction with lithium aluminum hydride, yielded XIII.