Lithium In Liquid Ammonia Research Articles

ChemInform Abstract: CYCLOPROPYL ORGANYL SULFIDES

Three methods were developed for the synthesis of cyclopropyl organyl sulfides, which are based on the reaction of cyclopropyl halides with either thiols or alkali metal thiolates in a superbasic medium, the reaction of cyclopropyllithium with diorganyl disulfides, and the reaction of cyclopropyl alkyl sulfides with lithium in liquid ammonia and subsequent reaction with organic bromo derivatives. In contrast, the cleavage of cyclopropyl aryl sulfides leads to the formation of lithium arylthiolates.

A convenient reduction of dialkylated tosylmethyl isocyanide

Dialkylated tosylmethyl isocyanides have been conveniently reduced to the corresponding hydrocarbons with lithium in liquid ammonia. This process has been successfully utilised in the synthesis of (Z)-9-tricosene - a sex pheromone of common house fly.

Cyclopropyl organyl sulfides

Three methods were developed for the synthesis of cyclopropyl organyl sulfides, which are based on the reaction of cyclopropyl halides with either thiols or alkali metal thiolates in a superbasic medium, the reaction of cyclopropyllithium with diorganyl disulfides, and the reaction of cyclopropyl alkyl sulfides with lithium in liquid ammonia and subsequent reaction with organic bromo derivatives. In contrast, the cleavage of cyclopropyl aryl sulfides leads to the formation of lithium arylthiolates.

Ester enolates from .alpha.-acetoxy esters. Synthesis of arylmalonic and .alpha.-arylalkanoic esters from aryl nucleophiles and .alpha.-keto esters

Eater enolates are generated by reductive α-deacetoxylation of α-acetoxy-α-arylmalonic esters or a-acetoxy-α-arylalkanoic esters with lithium in liquid ammonia or sodium α-(dimethylamino)naphthalenide in hexa- methylphosphoramide-benzene. Since the requisite α-acetoxy esters are available from aryl nucleophiles. the reductions provide effective new synthetic routes to arylmalonic esters and α-arylalkanoic esters. For example, 2-(p-isobutylphenyl)propionic acid (ibuprofen. a commercially important nonsteroidal antiinflammatory agent) is obtained in 73% yield overall from isobutylbenzene. Arenes, aryllithiums, or aryhrtagnesium halides react with α-keto esters, e.g., diethyl oromalonate, ethyl pyruvate, methyl phenylglyouxalate, or alkyl glyoxylates, to afford α-hydroxy esters. These are acetylated with acetic anhydride-triethylamine and p-(dimethylamino)pyridine as a catalyst. Reductive α-deoxygenation then allows replacement of the acetoxy group by hydrogen or an alkyl group.

ChemInform Abstract: REDUCTION OF A 3,4‐CYCLIC‐SUBSTITUTED 2H‐1‐BENZOPYRAN‐2‐ONE WITH LITHIUM IN LIQUID AMMONIA

AbstractDie Reduktion des Cumarinderivates (I) mit Li/NH3 führt zu den cis‐hydrierten Produkten (II)‐(IV) im Verhältnis (42:l4:44), die durch Jones‐Oxidation zum Lacton (II) übergeführt werden.

Reduction of a 3,4‐cyclic‐substituted 2H‐1‐benzopyran‐2‐one with lithium in liquid ammonia

AbstractReduction of the α,β‐unsaturated lactone system in 1‐hydroxy‐3‐pentyl‐7,8‐dihydro‐spiro[dibenzo[b,d]pyran‐9,2′‐[1,3]dioxolan]‐6(10H)‐one (3) with lithium in liquid ammonia leads to cis products.

An approach to taxodione involving biomimetic polyene cyclization methodology

A novel synthesis of 11,12-dimethoxyabieta-8,11,13-triene ( 4), involving the biomimetic cyclization of allylic alcohol 5 is described. This represents a formal total synthesis of taxodione ( 1), a tumor-inhibitory diterpenoid quinone methide. Treatment of the sodium salt of 8 with allyl bromide gave a 91% yield of allyl ether 19 which readily underwent a Claisen rearrangement to give (after methylation with dimethyl sulfate) the dimethoxy olefin 21 in 90% yield. Hydroboration with disiamylborane, followed by oxidative work-up gave alcohol 17 in 98% yield. Oxidation with Collins' reagent afforded 22 in 83% yield. which, upon treatment with isopropenylmagnesium bromide, gave allylic alcohol 23 in 91% yield. Conversion of 23 into chloro ketone 25 was readily effected in 80% yield via a chloro ketal Claisen rearrangement. This substance afforded epoxide 26 in 94% yield when treated with isopropenyllithium. Reduction of 26 with lithium in liquid ammonia gave the desired substrate 5 in 93% yield. When 5 was treated with trifluoroacetic acid in methylene chloride at ca −45° for 45 min, a 90% yield of the desired tricyclic material 6 was obtained. Conversion of 6 to dl-11,12-dimethoxy-abieta-8,11,13-triene ( 4) was effected in 59% yield by ruthenium tetroxide oxidation (to give 30) followed by sodium cyanoborohydride reduction of the corresponding tosylhydrazone of 30. Resolution of 30 involved the separation of the diastereomeric ketals 31. Conversion of d- 30 into d-11,12-dimethoxyabieta-8,11,13-triene ( 4) was effected in the aforementioned manner used in the dl-series.

Protonation, and reductive cleavage by lithium of the CS bond, in (methylthio)pentadienylic anions generated from various cis,trans‐isomers of 1‐(methylthio)‐1,3‐pentadiene and 1‐(methylthio)‐1,4‐pentadiene

AbstractTreatment of the various cis,trans‐isomers of CH3SCHCHCHCHCH3 and CH3SCHCHCH2CHCH2 with a slight excess of potassium amide in liquid ammonia, followed by quenching of the solutions thus obtained with ammonium chloride, gives, in all cases, the is isomer CH3SCH2CHCHCHCH2(> 90% trans) From the anionic solutions 1H NMR spectra have been recorded.Reductive cleavage of the CS bond of the anions CH3SCHCHCHCHCH2⊖ with lithium in liquid ammonia, followed by methylation, leads to almost complete recovery of CH3SCHCHCHCHCH3. During this cleavage, the double bond next to sulfur retains its configuration, while the configuration of the other double bond changes from trans to cis. It remains the same, however, on starting from a (methylthio)pentadiene with a cisC3C4 double bond. The ultimate result of the cleavage procedure with CH3SCHCHCH2CHCH2 is CH3SCHCHCHCHCH3: the configuration of the C1C2 double bond remains the same and the C3C4 double bond is always cis.

The dianion derived from N-methylphthalimide

Reduction of N-methylphthalimide with lithium in liquid ammonia provides a stable dianion which has been alkylated with various reagents.

Total synthesis of substituted (±)-6,6-dimethyl-B-norestra-1,3,5(10)-trien-17β-ols and their 9β-isomers

Total syntheses of (±)-1,4-dimethoxy-6,6-dimethyl-B-norestra-1,3,5(10)-trien-17β-ol(11a), (±)-2,3-dimethoxy-6,6-dimethyl-B-norestra-1,3,5(10)-trien-17β-ol (11b), and (±)-3-methoxy-6,6-dimethyl-B-norestra-1,3,5(10)trien-17β-ol (11c), have been carried out starting from 4,7-dimethoxy-3,3-dimethylindan-1-one (1), 5,6-dimethoxy-3,3-dimethylindan-1-one (2), and 4′-methoxy-3-methylbut-2-enophenone (4), respectively. Generally, it is found that the intermediate 6,6-dimethyl-B-norestra-1,3,5(10),8-tetraen-17β-ols (10), on lithium–liquid ammonia reduction, yield a mixture of 8β,9α- and 8β,9β-trienols, (11) and (12) respectively, in the ratio 1 : 1. This is due to the comparable stabilities of these two isomers. However, the reduction carried out in presence of aniline affords a higher percentage of the 8β,9α-trienol (11). The assignment of configurations is made by chemical and 1H n.m.r. analysis. Catalytic hydrogenation of the tetraenols (10) is shown to proceed via initial isomerisation to the corresponding 6,6-dimethyl-B-norestra-1,3,5(10),9(11)-tetraen-17β-ols (26), followed by hydrogenation from the β-side to give, exclusively, the 8β,9β-trienols (12).

Synthetic studies towards complex diterpenoids. Part 11. Stereochemically defined synthesis of the racemates of 1,2,3,4,4a,9a-hexahydro-7-methoxy-1-methylfluorene-1-carboxylic acid

Two simple synthetic routes to 1,2,3,4-tetrahydro-7-methoxy-1 -methylfluorene-1 -carboxylic acid (1b), a potential intermediate towards gibberellins, and its stereochemically defined transformations to three racemates of 1,2,3,4,4a,9a- hexahydro-7-methoxy-1 -methylfluorene-1 -carboxylic acid (4b)–(6b) are described. Catalytic hydrogenation of (1 b) yields a mixture of (5b) and (6b) in a ratio of ca. 95 : 5, whereas, lithium-liquid ammonia reduction of (1b) gives (4b) and (6b) in a ratio of ca. 23 : 77. A mechanism is proposed to explain the stereochemical results in the lithium–ammonia reduction of (1b) and related systems.

ChemInform Abstract: FUNCTIONALIZATION OF TRANS‐DECALIN. II. A SYNTHESIS OF DL‐ISOPETASOL FROM TRANS‐5‐OXODECALIN‐8A,2‐CARBOLACTONE

AbstractAusgehend von dem Lacton (Ia) wird über die Verbindungen (Ib) und (II)‐(IV) das Oxodecalinacetal (Va) synthetisiert und zu (Vb) epimerisiert.

ChemInform Abstract: A SIMPLE TOTAL SYNTHESIS OF (+)‐FERRUGINOL, (+)‐SEMPERVIROL, AND (+)‐PODOCARPA‐8(14)‐EN‐13‐ONE

AbstractDie aus (‐)‐α‐Cyclocitral (I) und den Phosphoniumsalzen (II) erhältlichen Styrylderivate (III) werden hydriert und die gebildeten Verbindungen (IV) zu den isomeren Podocarpan‐Derivaten (V) und (VI) cyclisiert.

Functionalization of trans-Decalin. II. A Synthesis of dl-Isopetasol from trans-5-Oxodecalin-8a,2-carbolactone

Abstract A stereocontrollcd synthesis of dl-isopetasol (1a) from trans-5-oxodecalin-8a,2-carbolactone (2a) is described. The key intermediate, trans-5,5-ethylenedioxy-1β,8aβ-dimethyldecalin-2-one (7b) was prepared by reductive methylation of trans-5,5-ethylenedioxydecahydrocyclopropa[d]naphthalen-2-one (5) for introducing the vicinal two methyl groups at C-1 and C-8a carbon atoms. The cyclopropyl ketone 5 was obtained by reduction of the acetal of 2a followed by (1) tosylation of the primary alcohol, (2) oxidation of the secondary alcohol with Corey’s NCS–DMS reagent, and (3) cyclization with t-BuOK. Reduction of 5 with lithium in liquid ammonia provides initially the corresponding enolate anion, which can be trapped with methyl iodide to give trans-5,5-ethylenedioxy-1α,8aβ-dimethyldecalin-2-one (7a), smoothly. Epimerization of 7a with MeONa in MeOH gave the desired intermediate 7b. Reduction of 7b with lithium in liquid ammonia gives the 2α-alcohol 8b, stereoselectively. The conversion of 8b into 1a was carried out as follows: (1) deacetalization of 8b followed with acetylation, giving trans-6α-acetoxy-4aβ,5β-dimethyldecalin-1-one (9b); (2) reduction of 9b with NaBH4 and subsequent dehydration affording the olefinic acetate 11; (3) oxidation of 11 with CrO3–pyridine complex, giving the enone 12; (4) aldol condensation of 12 with acetone followed by dehydration, isomerization of double bond, and hydrolysis, providing the desired 1a.

Applications of high-potential quinones. Part 13. Dehydrogenation of de-A-estra-5,7,9-trienes to styrenes

The de-A-estratrienes (1)–(6) yield the corresponding de-A-estra-5,7,9,14-tetraenes (8)–(13) by oxidation with an equimolar amount of dichlorodicyanobenzoquinone in dioxan at room temperature. The rates of dehydrogenation ate sensitive to changes in substituents at C-17. Similar rate ratios are observed for the alcohol–acetate pairs (1)–(2) and (3)–(5), indicating a mechanism involving direct attack at the benzylic position in both the phenols and their methyl ethers. Deoxygenation of the phenol (3) was carried out by cleavage of the diethyl phosphate ester with lithium in liquid ammonia, but could not be achieved by cleavage of the phenyltetrazolyl ether

A Simple Total Synthesis of (+)-Ferruginol, (+)-Sempervirol, and (+)-Podocarpa-8(14)-en-13-one

Abstract The Wittig reaction of (R)-(−)-α-cyclocitral with (3-isopropyl-4-methoxybenzyl)-, (4-isopropyl-3-methoxybenzyl)-, and (3-methoxybenzyl) triphenylphosphonium chloride afforded the styryl derivatives which were partially hydrogenated to the corresponding dihydro derivatives (18, 26, and 27). Intramolecular cyclization of 18 and 26 with anhydrous aluminium chloride followed by demethylation with boron tribromide gave (+)-ferruginol and (+)-sempervirol. The similar cyclization of 27 gave (+)-13-methoxypodocarpa-8, 11, 13-triene. This was reduced with lithium in liquid ammonia in the presence of ethanol and then treated with dilute hydrochloric acid to give (+)-podocarpa-8(14)-en-13-one, a versatile intermediate for natural diterpene synthesis.

Improved preparation of pregn-5-ene-3β, 16α, 20-triols and 5α-Pregnane-3α, 16α, 20-triols

The compounds named in the title were prepared by routes which included the reduction of suitable 16α,17-epoxypregnan-20-ones with aluminium amalgam to give 16α-hydroxypregnan-20-ones, and reduction of the 20-oxo function either with sodium borohydride to obtain the 3, 16α, 20β-triols or with lithium-liquid ammonia to obtain the 3, 16α, 20α-triols.

Electrical Conductivity and Thermoelectric Power of Concentrated Lithium‐Ammonia Solutions

AbstractThe electrical conductivity and thermoelectric power of solutions of lithium in liquid ammonia have been measured as a function of composition and temperature. The transition from the semiconducting to the metallic state has been observed in the intermediate concentration range, around 4.5 mole percent lithium. The obtained results are discussed in terms of the models put forward by Mott and others.

Mannich reaction in six-membered heterocyclic ?-ketones

The stereochemical principles of the reduction of 2,2-dimethyl-5-aminomethyl-4-oxotetrahydropyrans with lithium aluminum hydride, sodium borohydride, aluminum isopropoxide, and lithium in liquid ammonia were investigated by determination of the dependence of the quantitative ratio of the resulting epimeric amino alcohols in the mixtures on the character of the reducing agent and its concentration and the nature of the solvent. The individual geometrical isomers of the amino alcohols were isolated, and their structures were established by PMR and IR spectroscopy.

Double ring opening of bridged dicyclopropyl ketones upon reduction by lithium in liquid ammonia

Double ring opening of bridged dicyclopropyl ketones upon reduction by lithium in liquid ammonia