Synthesis of Bicyclo[4.2.0]Octa-3,7-Diene-2,5-Diones

The bicyclo[4.2.0]octa-3,7-diene-2,5-diones (1) are of interest in that they are valence isomers of 1,4-cyclooctatetraenoquinones. The most obvious route for the formation of such compounds is the [2+2] photoaddition of alkynes to p-benzoquinones. Such a reaction has been observed in the case of 1,4-naphthoquinones. With p-benzoquinones, however, it has been observed in the case of 2-methoxy-p-benzoquinone (2a) alone, while p-benzoquinone (2b) and chloranil (2c) give products derived from addition of acetylenes to a carbonyl rather than an ethylenic bond; ^3,4 such products also accompany the products from 1,4-naphthoquinones referred to above.^1,3     

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     

Convenient Synthesis of 2-Vinylindoles

A convenient, two-step synthesis of 2-vinylindoles is described from the easily accessible (E)-ethyl-α-allyl-2-nitrocinnamates. Ethylcinnamates (1a and 1b) on reaction with triethylphosphite provide ethyl-2-allylindole-3carboxylates (2a and 2b ) along with minor amounts of their N-ethoxyderivatives (4a and 4b). Alkaline hydrolysis of 2a and 2b provide (E)-2-vinylindoles 3a and 3b in 60 and 67% yield respectively.     

An Improved Total Synthesis of (±) - Podocarpic Acid by a Cyclialkylation Route

A number of total syntheses of (±) - podocarpic acid (i) have been described¹ King, King and Topliss² first identified one of the products from nonstereo-selective cyclization of (4) with polyphosphoric acid as (±)- ethyl-O-methylpodocarpate (2) and correlated that with the corresponding acid (3), prepared in an extremly poor yield (ca 0.4%)³ by Bhattacharyya³, and Haworth and Moore⁴ by cyclization of (5) with a mixture of sulfuric acid and acetic acid. More recently Mancini, Fringuelli and Taticchi⁵ prepared (3) (in 4.8% yield) by repeating Howorth¹ s cyclization of (4). In continuation of our studies on cyclialky-     

Synthesis of 2-Aryl-1H-s-Triazolo[1, 5-a] Benzimidazoles

2-Aroylaminobenzimidazoles (2) have been converted into 1(2-benzimidazolyl)-5-aryl-1H-tetrazoles (4) by treatment with PCl₅ followed by azidation with NaN₃ in aqueous acetone solution. Pyrolysis of 4 in diphenylether yielded 2-aryl-1H-s-triazolo [1,5-a] benzimidazoles (6). The product of benzylation of 6a has been characterised. A reasonable pathway for the formation of 6 from 4 has been suggested.     

Synthesis of N-[2-S -(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-Thio-D-Lactoyl]-L-alanyl-D-isoglutamine

Abstract

N-[2-S-(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-thio-D-lactoyl]-L-alanyl-D-isoglutamine, in which the oxygen atom at C-3 of N-acetylmuramoic acid moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) has been replaced by sulfur, was synthesized from allyl 2-acetamido-2-deoxy-β-D-glucopyranoside (1).

Treatment with sodium acetate of the 3-O-mesylate, derived from 1 by 4,6-O-isopropylidenation and subsequent mesylation, gave allyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-allopyranoside (4). When treated with potassium thioacetate, the 3-O-mesylate, derived from 4, afforded allyl 2-acetamido-3-S-acetyl-2-deoxy-4,6-0-isopropylidence-β-D-glucopyranoside (6). S-Deacetylation of 6, condensation with 2-L-chloropropanoic acid, and subsequent esterification, gave the 3-s[D-1(methoxycarbonyl)ethyl]-3-thio-glucopyranoside derivative (7). Coupling of the acid, derived from 7, with the methyl ester of L-alanyl-D-isoglutamine, and subsequent hydrolysis, yielded the title compound.     

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 2-Methyl-3-acetyl-5-oxo-5H-[1]benzopyrano[2,3-b]pyridine

For our synthetic work we needed the title compound. Literature survey revealed that 2-amino-4-oxo-4H-[1] benzopyran-3-carboxaldehyde (2-amino-3-formylchro-mone) can undergo condensation with diethyl malonate (or ethyl cyanoacetate) forming ethyl 2-hydroxy(or amino)-5-oxo-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxylate¹.     

New Homologation Procedures of Carbonyl Compounds by Means of Diethyl[trimethylsilylethoxymethyl]phosphonate

Abstract

The lithiated carbanion of the phosphonate 1 prepared by means of s-BuLi at -78°C in THF can be treated with C1Si(CH₃)₃ transforming 1 into its α-Si(CH₃₎₃ substituted derivative 2. Whereas the anion of 1 is thermally unstable at temperatures exceeding -70°C the preparation of the corresponding carbanion of 2 by means of s-BuLi and the subsequent reaction with carbonyl compounds can be carried out at temperatures about -30°C illustrating the carbanion stabilizing effect of the α - silyl group. The phosphonate 2 is very suitable to effect conversion of many aldehydes and ketones via the vinylphosphonate-type 3 (applying a Peterson elimination) either to the homolocles esters 4 or the special α -hydroxyesters 5.     

Crystalline Methyl β-L-Pfamnofuranqside From Fischer Glycqsidatiok of L-Rhamnose

Flash chromatography of the mixture obtained by reaction of L-rhamnose with methanol in the presence of cation-exchange resin, in addition to methyl α-L-rhamnofuranoside (3) and methyl rhamnopyranosides 1 and 2 gave methyl β-L-rhamnofuranoside (4) in 8% yield. ¹³C and ¹H NMR spectra of 3 and 4 as well as their calculated conformation in solution are discussed.     

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.     

Sesquifulvalene Trapping as a [12+2] Adduct with Tetracyanoethylene

Sesquifulvalene (1) is a substance of considerable theoretical interest¹ which is expected to have a significant contribution to its structure from the dipolar resonance form 1b,² and hence an exceptionally low bond order for the central double bond. Although a wide variety of annelated and otherwise substituted sesquifulvalenes have been prepared and characterized,³ the parent substance has proved remarkably elusive. Very recently, a preparation of 1 in crystalline form has been reported, based upon elimination of an acetoxy-11,12-dihydrosesquifulvalene derivative.⁴     

Synthesis and Stereochemical Studies of Derivatives of 1,4-Dimethyl-2-phosphabicyclo[2.2.1]heptane

Abstract

1,4-Dimethyl-2-phenyl-2-phosphabicyclo[2.2.1]heptane 2-oxide 1 was prepared by the reaction of 2,5-dimethyl-1,5-hexadiene with PhPCl₂-AlCl₃: stereo-assignments of the exo and endo isomers were established by ¹³C NMR spectroscopy (using lanthanide shift reagents) and by x-ray crystal structures. The isomers of 1 were separately reduced (phenylsilane) to give the phosphine derivative; in turn the phosphines were thermally equilibrated at 190°C to give a predominance (70%) of the exo-phenyl isomer.     

Synthesis of 2-Aroylimjnopyrimido[3,2-B]-1,2,4-Thiadiazolines

N-Aroyl-N′-(pyrimid-2-yl)-thioureas (2) have been synthesised by the reaction of 2-amino pyrimidines (1) with aroyl chlorides and ammonium thiocyanate in acetone- Cyclisation of 2 with PCl₅ in POCl₃ and as well as by oxidising agents gave 2-aroyHrninopyrimido[3,2-b]-1,2,4-thiadiazolines (3).     

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.     

Synthesis and Structure Elucidation of 8-Methyl- and 9-Methyl-exo-2-carbomethoxy-endo-tricyclo[5.2.1.02,6]deca-3,8-dien-5-ones

A mixture of 1-methyl- and 2-methyl-1,4,4a,8a,-tetrahydro-endo-1,4-methano-naphthalene-5,8-diones ( 2 & 3 ) was chemically transformed into separable methyl substituted tricyclo[5.2.1.0^2,6]decadienones 7 , 8 & 9 . The structure of 8 & 9 were elucidated via Cope rearrangement of their corresponding allylic alcohols ( 10 & 11 ) to furnish 12 & 13 respectively.     

A Useful Synthesis of 2-Methyl-2,3-dihydrofuro [2,3-b] Quinolines

A convenient, general synthesis of 2-methyl-2,3-dihydrofuro [2,3-b] quinolines is described from o-nitrobenzaldehydes. The benzaldehydes (la-c) on reaction with phosphorane 2 provide (E)-ethyl-α-allylcinnamates (3a-c) in high yields. These esters 3a-c on reduction followed by acid catalysed cyclisation give 2,3-dihydrofuro [2,3-b] quinolines (5a-c).     

Synthetic Approaches to Taxodione. Synthesis of Methyl 12-Oxopodocarpa-5,9(11)-diene-8β-Carboxylate

In connection with studies leading to the total synthesis of taxodione¹ (1), we required the tricyclic enone 3. We have previously described² an AB→ABC approach to this intermediate which was flawed by a low yield in the penultimate closure of the C ring (2→3). We now wish to report an alternate synthesis of 3 which involves a BC→ABC approach for the construction of this tricyclic system.     

A Convenient Synthesis of 3-Methoxyphthalic Anhydride

Many antibiotics of the anthracycline family¹ possess structures for which 3-methoxyphthalic anhydride (1) would be a suitable synthon² in a total synthesis. A classic synthesis of (1) has employed 3-nitrophthalic acid³ but, in our hands, proceeded in low overall yield. Recent syntheses have utilized the Diels Alder reaction of dimethyl acetylenedicarboxylate (2) with 1-methoxy-1,3-cyclohexadiene,⁴ 1,4-diacetoxybutadiene,⁵ 2-acetoxyfuran,⁶ 2-methoxyfuran⁷ or furan⁸ to obtain 3-hydroxyphthalic acid or a derivative. We now wish to report a convenient Diels-Alder synthesis of (1) from 3-methoxy-2-pyrone (3).     

Darstellung Der Isomeren 1,6-DI-O-Acetyl-3,4-Didesoxy-α, β-D-Glycero-Hex-3-Enopyrahos-2-Ulosen

Abstract

Prolonged treatment of tetra-O-acetyl-1, 5-anhydro-hex-1-enitols (“tetra-O-acetyl-hydroxy-glycals”) 3 and 5 with BF₃ in CH₂Cl₂ at RT lead to anomeric mixtures of the title compounds 2 and 4a, the α-anomer 4a dominating. Reaction of 5 gave the higher yields of 4a (71%) and 2 (12%), the results being accounted mechanistic grounds. The same reaction performed in an aromatic solvent, like toluene, gave rise to competing C-alkylation., The ortho and para-tolyl derivatives 6 and 7, also with enone structure, were isolated in a combined maximum yield of 40% from 5. β-Enone 2 was also prepared in moderate yield by thermolysis of β-d-glucopyranose pentaacetate (1). In this case no α-anomer 4a was detected.