An Efficient Stereoselective Synthesis of a Tricyclic Intermediate for the Synthesis of Derivatives of Abietic and Podocarpic Acids

For many years the synthesis of diterpene acids has attracted the attention of organic chemists. Kröniger and Wheeler¹ reported that the condensation of the dimethylate 1a with methyl malonate gave the cis compound 2a which on heating with palladised charcoal was converted into the trans isomer 3a. Compound 3a is a promising intermediate in the synthesis of derivatives of both abietic and podocarpic acids, while 2a could be a starting material for the synthesis of cis fused diterpene acids. However, the route to 2a and 3a was inefficient; 1a was only available as the minor component of a mixture with its epimer 1b; and the yield for the stage 2a + 3a was poor.     

1-Thioglycopyranosyl Esters of N-Acylamino Acids

Abstract

Fully protected 1-thioglycopyranosyl esters of N-acylamino acids (5, 6, and 7) were prepared by condensation of methyl 2, 3, 4-tri-O-acetyl-1-thio-β-d–glucopyranuronate (1), 2, 3, 4-tri-O-acetyl-1-thio-l–arabinopyranose (2), and 2, 3, 4-tri-O-acetyl-1-thio-D-arabinopyranose (3) with pentachlorophenyl esters of N-acylamino acids in the presence of imidazole. The ¹³C NMR chemical shifts of the starting 1-thio sugars and the 1-thiol ester products are reported.     

The structure of cis and trans lsomers of 1-(p-Bromobenzylidene)-2-indanone

Abstract

In this communication we wish to report an interesting case of the isolation and characterization of the cis and trans isomers of 1-(p-bromobenzylidene)-2-indanone and their ketals. Prior to this work, Hoogstreen and Trenner² had reported on the cis and trans isomers of 1-(p-chlorobenzylidene)-2-methyl-5-methoxyindenylacetic acid. The condensation of 2-(N-morpholinyl)-indene (1, prepared by the reaction of 2-indanone³ and morpholine) with P-bromobenzaldehyde was conducted by refluxing them in the presence of acetic acid for 4 hours. Acid hydrolysis of the reaction mixture followed by dry column chrcmatography over sillica gel using a fraction collector afforded two iscmeric monobenzylidenes, compounds 2(36.6%, mp 110–111°)and 3(1.3%, mp 115–116°) and a dibenylidene, compound 4 (8.7%, mp 205°). The relative rations of the mono- and dibenzylidenes seemed to depend on the reaction conditions. Higher yields of the monobenzylidenes 2 and 3 were obtained by conducting the reaction in the presence of UV light. The structures of these monobenzylidenes were established as cis and trans isomers of 1-(p-bromobenzylidenes)-2-indanone on the Basis of elemental analyses and ir and nmr spectroscopy. The ir spectra⁴ (CHCl₃)

of compounds 2 [1725 (c=0), 1620 (c=c)cm^?1] and 3[1710 (c=o), 1570, 1600 (c=c) cm^?1] were consistent with the structures. The molecular ion peaks as well as the fragmentation patterns in the mass spectra of both these compounds were consistent with the assigned structures. Before going into the omr discussion it should be pointed out that treatment of compound 2 with athylene glycol in the presence of p-toluene sulfonic acid produced two ketals, 5 (38.3% mp, 118–120°) and 6 (30.6% mp, 125–126°). As depicted; the ketals 5and 6 were also found (by omr) to be related to each other as cis and trans isomers. Furthermore, each of them could be hydrolyzed with acid to the corresponding monobenzylidenes 2 and 3 without any isomerization. However, UV irradiation of compounds 2 and 3 gave equilibrium mixtures containing both the isomers, indicating isomerization had occurred under photolytic conditions.     

N-(Chlorosulfinyl)-Imidazole as a New Imidazole Transfer Reagent1

The usefulness of diimidazoles² such as N, N′-carbonyldi-imidazole (1), and N, N′-thionyldiimidazole (2) in organic synthesis has been accumulated recently. In connection with the continuing our studies on the reaction using 1 or 2 ³ (carbonyl, thionyl, and imidazole transfer reactions), our particular interest was focused on the synthesis of N-(chlorosulfinyl)-imidazole (3) in which one imidazole group in 2 was replaced by the other leaving group (Cl). Also, 3 was interesting for preparative purposes as a chlorine atom could be introduced via the addition reaction of 3 to carbonyl compounds as known in the reaction of 1 or 2 with ketones.     

Stereoselective Synthesis of 3-C-Branched-Chain Sugars by Aldol Reaction of Furanos-3-Uloses with Acetone

Abstract

Aldol reaction of 1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-erythro-pentofuranos-3-ulose (1) with acetone in the presence of aqueous K₂CO₃ afforded 3-C-acetonyl-1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-ribofuranose(2). Similar reaction of 1,2:5, 6-di-o-isopropylidene- α-D-ribo-hexofuranos-3-ulose (3) afforded 3-C-acetonyl-1,2:5, 6-di-o-isopropylidene- α-D-allofuranose (4) and (1R, 3R, 7R, 8S, 10R)-perhydro-8-hydroxy-5,5,10-trimethyl-2,4,6,11,14-pentaoxatetracyclo[8,3,1,0^1,8,0^3,7] tetradecane. The stereochemistry of the new chiral centers were determined by ¹H NOE experiments.     

Synthesis of 2′,3′-Dideoxy-2′-Fluorokanamycin A

2′,3′-Dideoxy-2′-fluorokanamycin A (23) was prepared by condensation of 6-azido-4-0-benzoyl-2,3,6-trideoxy-2-fluoro-α-D-ribo-hexopyranosyl bromide (13) and a protected disaccharide (19). Methyl 4,6-0-benzylidene-3-deoxy-β-D-arabino-hexopyranoside (5) prepared from methyl 4,6-0-benzylidene-3-chloro-3-deoxy-β-D-allo-hexopyranoside (1) by oxidation with pyridinium chlorochromate followed by reduction with Na₂ S₂O₄ was fluorinated with the DAST reagent to give methyl 4,6-O-benzylidene-2,3-dideoxy-2-fluoro-β-D-ribo-hexopyranoside (7). Successive treatment of 7 with NBS, NaN₃ and SOBr₂ gave 13. The structure of the final product (23) was determined by the ¹H and ¹⁹F and shift-correlated 2D NMR spectra.     

A Convenient Synthesis of 2,3-Diphenyl-2-cyanooxiranes

Several studies¹ have been reported on the synthesis of 2,3-diphenyl-2-cyanooxiranes. Kohler and Brown^la synthesized the oxirane in ca. 30% yield by reaction of desyl chloride with potassium cyanide in aqueous alcohol. However, the method which they employed seems to be rather complicated. Such reaction of desyl bromide with cyanide ion has not been studied in detail. We now report that cis- and trans-2,3-diphenyl-2-cyanooxiranes (2a-d and 3a-d) are conveniently obtained in good yields by reaction of 4′-substituted desyl bromide (1a-d) with 40% aqueous potassium cyanide in a mixture of dichloromethane and triethylbenzylammonium chloride (TEBAC); the total yield of 2c and 3c, for example, was as high as 86%. When cethyltriethylammonium bromide was used as a     

The Reaction of N-Phenyliminoketenylidenetriphenyl-phosphorane with α,β-Unsaturated Carbonyl Compounds. Synthesis of New Pyran Derivatives

Abstract

The reaction of N-phenyliminoketenylidenetriphenylphosphorane [a] (1), with 2-benzylidene-1, 3-indandione (2), 1,2-diphenyl-3,4-pyrazolidenedione (3)and/or 5-benzylidene barbituric acid (4) has been investigated. When ylide 1 was allowed to react with compounds 2, 3 or 4 in THF at ambient temp. the corresponding new pyrano-phosphoranylidenes 5, 6 or 7 were obtained. The elemental microanalyses, IR, ¹H NMR, ³¹P NMR and MS data agree with the structure of the cyclic iminophosphoranes by [4+2]-cycloaddition and exclude 4-membered ring structure by [2+2]-cycloaddition. When the Wittig reaction was carried on the pyrano-phosphoranes 5, 6 or 7 using p-nitrobenzaldehyde, the exocyclic olefins together with triphenylphosphine oxide were isolated.     

A Conventient Synthesis of 3-Hydroxy-4-chromanone Using Iodobenzene Diacetate

A useful synthesis of 3-hydroxy-4-chromanone (6) is not currently available. Lead tetraacetate oxidation of 4-chromanone (4) yields the C(3) acetoxy derivative but this compound could not be deacetylated to 6.¹ Recently Donnelly and Maloney reported² that the Algar-Flynn-Oyamada reaction (H₂O₂/CH₃OH/NaOH), which is commonly used for the conversion of o-hydroxychalcones (1) into 3-hydroxyflavanone (2) and 3-hydroxyflavones (3), does not yield 6 when applied to o-hydroxya-crylophenone 1 (R = H). The authors found that under less basic conditions using K₂CO₃ some 6 is formed but the major product is catechol. These observations clearly indicate the necessity of developing a method for making 6. The present note describes a staightforward way of preparing 3-hydroxy-4-chromanone (6) in good yield.     

Synthesis of γ-Lactone of 1R-CIS 2,2-Dimethyl-3-(2,2,2-tribromo-1-hydroxyethyl)cyclopropane Carboxylic Acid,A Key Intermediate for Deltamethrin,From (+)-3-Carene

1R-cis-2,2-Dimethyl-3-(2,2-dibromovinyl)cyclopropane carboxylic acid¹ (1), the acid moiety of the highly potent photostable pyrethroid deltamethrin (2) has been obtained either by a Wittig reaction on 1R-cis-caronaldehyde ester (3) employing 1, 1-dibromomethylenetriphenylphosphorane or from the bicyclic tribromo-lactone^2,3 (4) by reaction with zinc and acetic acid. Lactone (4) is thus an important intermediate in the deltamethrin synthesis.     

Cyclopropanotetrahydropyridines

In recent syntheses of eburnamonine,¹ aspidospermidine² and quebrachamine² the copper-catalyzed, diazoacetic ester-induced conversion of tetrahydropyridine 1 into the cyclopropanopiperidine 2 was a crucial, early reaction step. It became of interest to apply this reaction to dihydropyridine equivalents of 1, i.e. 3 and 4, in connection with the development of routes of synthesis directed towards alkaloids of the pandoline or velbenamine types. This Communication illustrates the preparation and cyclopropanation of dihydropyridines 3 and 4.     

Reaktionen Mit Trimethylsilylhalogeniden an Derivaten Der Digitoxose

Abstract

Treatment of methyl 3,4-di-O-acyl-2,6-dideoxy-α-D-ribo-hexo-pyranoside 1 or 2 with trimethylsilyl halide leads to the formation of a complex mixture of α-D-ribo-hexopyranosyl halides 3 or 5 together with the educts 1 or 2 as well as their β-anomers 8 or 9. The bromides 3 and 5, suitable for glycosidations, are preferably obtained by reaction of the digitoxose acetate derivatives 6 and 7, respectively, which in turn are prepared from 1 and 2 by mild acetolysis. Further reaction of the halides 3 to 5 with trimethylsilyl halides gives rise to a quantitative formation of the 2,3,6-trideoxy-4-0-acyl-3-halo-α-D -arabino-hexopyranosyl halides 10 to 12. In another reaction sequence starting with the olivose triacetate 20 the formation of 10 via the halide 13 is demonstrated. Structural evidence for the halides 10 to 12 is given by ¹H NMR data as well as by analyses of their glycosides 14 to 19. The results support a mechanistic interpretation for the formation of 10 to 12 via a 3,4-acetoxonium ion as the key intermediate obtained from 3 by an S_Nfi and from 13 and S_N2i step. Final conversion into the terminal halodeoxy compounds 10 to 12 proceeds by and S_N2 reaction with the halide ion.     

A New Synthesis of 3-Deoxy-D-arabino-hexose and its Tautomeric Equilibrium

Abstract

The title compound was synthesized in four steps from D-glucono-1,5-lactone. Reduction of 2,4,6-tri-O-benzoyl-3-deoxy-D-arabino-hexono-1,5-lactone (1) with disiamylborane afforded 2,5,6-tri-O-benzoyl-3-deoxy-D-arabino-hexopyranoae (2) which, on debenzoylation, gave 3-deoxy-D-arabino-hexoae (3). Tautomeric equilibrium of 3 was studied by ¹H and ¹³C NMR spectroscopy.     

New Preparation of Cyclic Acyloxyphosphorane by Reaction of Glyoxylic Acid with Phosphorus(III) Compounds

We have recently found that the reaction of α-keto acids (1) with phosphorus (III) compounds (3) yielded cyclic acyloxyphosphoranes(C-AOPs, 4), a new class of pentacovalent phosphorus species having a P-OC(O) group.^{1, 2)} The present paper deals with a new reaction of glyoxylic acid (2) with 3 to give C-AOPs (5) having no substituent at the C-3 position. 1 is an α-keto acid whereas 2 can be taken as an α-formyl acid. Although it is well known in the field of organic chemistry that the formyl group often behaves differently from a keto group, the reaction of 2 with 3 provides an example in which both groups behave in a similar manner.     

Oxygenation of Trimethylsilylallenes Readily Obtainable from Organoboranes. Syntheses of 1-Trimethylsilyl-1-alkyn-3-ones and 1-Trimethylsilyl-1-alkyn-3-ols

Abstract

Recently we have reported that the reaction of sodium methoxide with ate-complexes (1) readily prepared from trimethyl-silylpropargyl phenyl ether and organoboranes gives trimethyl-silylallenes (2) selectively (eq. 1).¹ In an attempt to find a new synthetic application of such silylallenes (2), the oxidation of 2 was examined. Although the usual oxidants such as m-chloro-perbenzoic acid were found to be unsuitable for the oxidation of the silylallenes, it was discovered that 2 was autoxidized at room temperature to propargylic hydroperoxide (3) (eq. 2). For example, the acidified starch-iodine test² strongly suggested the presence of the organic hydroperoxide in the reaction mixture obtained from 1,2-heptadienyltrimethylsilane (2, R=Bu) and oxygen. The hydroperoxide (3, R=Bu) was isolated in a 40% yield by distillation, 45–48 [ddot]C/0.1 mmHg. In the infrared spectrum, the OH stretching frequency appears at 3430 cm^?1 and the C°C at 2180 cm,^?1     

Synthesis of Some Non-Conjugated Dienones in the Retro-α-Ionone Series1

In the course of a study on the photochemical and thermal behaviour of β,γ-δ,ε-dienones^1-4, (E)-retro-α-ionone (2a) and a series of methylated (3, 4) and desmethyl analogues (2b-2e) have been synthesized by a simple deconjugative isomerization of the corresponding conjugated dienones in strong alkaline solution. 3-Methyl- (3) and 3,3-dimethyl-retro-α-ionone (4) have been prepared by addition of methyl chloride to a strongly alkaline solution of β-ionone (1a).⁵     

Synthesis of C-Glycosyl α-Glycines

Abstract

A scheme of asymmetric synthesis of C-glycosyl α-glycines is described. Reductive hydrolysis of 2-deoxy-3,5-di-O-p-toluoyl-β D-erythropentofuranose 1-cyanide (4) in the presence of N,N-diphenylethylenediamine gave the imidazolidine 5, which was converted to 2,5-anhydro-3-deoxy-4,6-di-O-p-toluoyl-β-D-allose (3)by acid hydrolysis. The aldehyde (3), chiralamine, benzoic acid and t-butyl isocyanide four component condensation afforded in good yield two diastereomeric adducts (6a and 6b), which were separated by column chromatography and deblocked to furnish 2-deoxy-β-D-erythropentofuranosyl R and S-glycines (1a) and (1b).     

Total Synthesis of (±) Flavipucine

In 1972 we proposed¹ structure 3 for flavipucine, an antibiotic from an Aspergillus flavipes strain. Later we reported² a novel reaction of 6-methyl-4-hydroxy-2-pyridone with α keto aldehydes which provided 1a from isobutylglyoxal and it was stated that we believed 1a would serve as a key intermediate in the total synthesis of flavipucine 3.     

A Convenient Synthesis of 5-Bromo-2-Pentanone

During a series of studies aimed at the total synthesis of pentacyclic triterpenes¹ we have examined the reaction of enollactones of type 1 with a variety of Grignard reagents. ^1c,2 In one of our problems we required the organometallic reagent 2a derived from the title compound 2b. A previous literature report for the preparation of this compound involved the reaction of α-acetylbutyrolactone 3 with aqueous HBr followed by steam distillation.³ In our hands the yields of 2b via this route were non-reproducible and at best, less than 15%.     

Carbon Atom Insertion: A One-Step Synthesis of Tricyclo[3.2.1.02,7]octanes and Tricyclo[4.1.0.02,7]heptanes from Cyclohexenes1

Reinarz and Fonken have reported² that the dibromocarbene adduct (1) of 1-methylcyclohexene, upon reaction with methylllthium at 0° in ether, produced exclusively the bicyclobutanes 2 and 3 in relative yields of 60% and 40%, respectively. We have prepared 1 by the phase-transfer method³ of Makosza and Fedorynski in a yield of 67%, found these previous results to be completely reproducible in our hands, and determined the combined yield of the two products (2 and 3) to be 67% also. Thus, the overall