Synthesis and Stereochemical Studies of 1-Phosphabicyclo[4.4.0]decane and 4- t -Butylphosphorinane Derivatives

Abstract

The title compounds and their derivatives have been prepared in good yield. Several of the synthetic steps are novel and have general applicability. Isomer assignments for these materials were based upon nmr and x-ray data. A two bond phosphorus-carbon coupling Karplus relation has been established for phosphines and applied to the systems under investigation. Extensive stereochemical studies were conducted. The conformational energy barrier in cis-“phosphadecalin” (2) was estimated to be 12.3–13.6 kcal/mol. Hydroxide ion attack on cis-phosphonium salt 5 went with retention at phosphorus, while cis or trans 4 proceeded with considerable inversion. Nucleophilic displacements on derivatives of phosphorinane generally went with inversion of configuration.     

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.     

SN2′ Addition of Organometallic Reagents to β′-Amino Cyclohexenyl Sulfone Derivatives

Organolithium reagents add to cyclohexenyl sulfone 12 to provide β-amino sulfones that can be eliminated to afford cis- adducts 17a-c. Cuprate reagents undergo trans addition to cyclohexenyl ammonium salt 13 to generate the isomeric vinyl sulfones 18a-c. This stereochemistry is opposite to what had been previously observed in cyclopentenyl derivatives; mechanistic rationale is provided.     

Synthesis of Some Novel Heteropolyquinanes

Synthesis of structurally novel aza-and oxa-polyquinanes from the abundantly available cis,syn,cis-triquinane dione 1 via transannular nucleo-phillc additions is reported.     

A General Method for Stepwise Elongation of the (1→5)-α-D-Arabinofuranan Chain

Condensation reaction of 3,5-di-O-benzoyl-1,2-O-(1-cyanoben-zylidene)-β-D-arabinofuranose (2) with benzyl and allyl 2,3-di-O-benzoyl-5-O-triphenylmethyl-α-L-arabinofuranosides (5a and 5b) in methylene chloride in the presence of triphenylcarbenium tetrafluoroborate as catalyst under high vacuum gave α-(1→5)-linked dimeric D-arabinofuranoside derivatives (6a and 6b). One of the dimeric compounds (6a) was debenzoylated, triphenylmethylated, and rebenzoylated to give a dimeric homolog of 5a (8). Similarly for the preparation of 6a, 8 was condensed with 2 to provide an α-(1→5)-linked trimeric D-arabinofuranoside derivative (9). Further elongation of the glycoside chain might be possible in the same way.     

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.     

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.     

Synthesis of Amino-Dideoxy-Dl-Pentopyranoses and Their Ureido Derivatives

Abstract

Various 4-deoxy-α or β-erythro or threo-pentopyranoses aminated on position 1 [6 and 19]. 2 [38] or 3 [9, 22, 23, 24, 32 and 35] were synthesised from 2-methoxy-5,6-dihydro-2H-pyran [1] and methyl 2,3-anhydro-4-deoxy-α and β-DL-erythro-pentopyranoside [11]. Different reactions were investigated including azidation. cis-oxyamination, epimine formation and oxirane aminolysis. All these amino sugars were converted into their chloroethylureido derivatives.     

Organic Synthesis by Means of Metal Complexes. X1Copper Catalyzed Oxidation of o-Phenylenediamine to Mucononitrile

This paper describes a simple stereospecific synthesis of cis,cis-mucononitrile and its derivatives in hig hyields. The procedure is based on the oxidation of o-phenylenediamine derivatives with molecular oxygen catalyzed by cuprous salts. Oxidative coupling of aniline with molecular oxygen catalyzed by cuprous chloride gives azobenzene². Also it is known that o-phenylenediamine (PDA) is oxidized in the presence of ferric³, Cobaltous⁴, and cupric chlorides⁵to afford 2,3-diaminophenazine or 2-amino-3oxophenazine. The formation of a metal nitrogen bonded intermediate, followed by intermolecular reaction was postulated in these oxidation reactions.^6,7.Mechanistic consideration of these reactions leads us to expect that the oxidation of PDA with molecular oxygen under selected conditions should proceed intramolecularly with ring claevage to give mocononitrile(MNL). PDA is converted into MNL by using stoichimetricamount of nickel peroxide⁸or lead terraacetate⁹, but the yields are low. We now wish to report a selective oxidative ring cleavage of PDA. rather than the phenazine formation, to give MNL in a very high yield.     

Synthesis of (±)-cis-Calamenene;

Hydroboration of 4 furnishes a mixture of primary alcohols 5 and 6. The stereochemistry of the crystalline half ester 7 has been established by X-ray studies. While the oxidation of 5 with Jones reagent furnishes the aldehyde 9 in low yield due to the formation of the by product 3, oxidation with Moffatt reagent furnishes the aldehyde 9 in satisfactory yields. cis-Calamenene 1 has been prepared from 9.     

Synthesis of Potential Antimicrobial Agents from Maltose. III. Introduction of an Amino Group Into the 3′-Position of 1,6-Anhydro-Disaccharides

Abstract

Regioselective cleavage of 1,6-anhydro-maltose (1) with periodate and the subsequent recyclization with nitromethane gave 1,6-anhydro-3′-deoxy-3′-nitro-disaccharides (3). Three diastereomers, prepared by benzylidenation of 3, were separated by column chromatography. Each of 4′,6′-O-benzylidene derivatives successively underwent debenzylidenation, reduction of the nitro group, and peracetylation to give 3′-acetamido-3′-deoxy-disaccharide derivatives (7, 8, and 9). The configurations of the 3-amino sugar moietres in 7 (D-gluco), 8 (D-manno) and 9 (D-galacto) were determined on the basis of the ¹H NMR data. The main product (7) was further modified to the 6-deoxy-6-nitro derivative.     

A Convenient Route To 1,2-Dibenzoyl-1-Arylethylenes

Short and convenient syntheses of 1,2-cis-dibenzoyl-1-ary 1-ethylenes 5a-e, 6 and 8a-d from the corresponding aryl ethers and dibenzoyl acetylene have been developed using boron trifluoride-etherate or aluminium chloride as catalyst.     

Synthesis of the Four Configurational Isomers of N-Benzoyl-2, 3, 6-Trtdeoxy-3-C-Methyl-3-Amino-L-Hexose from the (2S, 3R)-Diol Obtained from α-Methylcinnamaldehyde by Fermentation with Baker'S Yeast

Abstract

The erythro and threo chiral C₅ methyl ketones (4) and (5), prepared from the (2S, 3R)-methyl diel (1b), were converted into the phenylsulfenimines (6) and (7), which, in turn, on reaction with allyl-magnesiutn bromide, yielded after acid hydrolysis and benzoylation, the diastereoisomeric C₈-N-aminodiol derivatives (9) and (11), with threo stereochemistry relative to positions 4 and 5. Ozonolysis of (9) and (11) yielded the l-arabino and l-xylo 3-O-methyl branched aminodeoxysugar derivatives (13) and (15), respectively. Using diallylzinc as the reagent, the diastereoisomeric erythro products (8) and (10) were obtained. The latter materials gave the l-ribo-and l-lyxo-(lL-vancosamine) derivatives (12) and (14) upon oxonolysis. The ¹H and ¹³C NMR spectra of the four isomeric aminodeoxysugar derivatives (12)—(15) were discussed.     

Derivatives Of α-Cyclodextrin and the Synthesis of 6-O-α-D-Glucopyranosyl-α-Cyclodextrin

Abstract

Regioselective silylation of α-cyclodextrin with tert-butyl-dimethylsilyl chloride in N, N-dimethylformamide in the presence of imidazole gave, in 75% yield, the hexakis(6-O-tert-butyldimethylsilyl) derivative 2, which was transformed into the hexakis(2,3-di-O-methyl, 6-O-methyl, 2,3-di-O-propyl, and 2,3-di-O-acetyl) derivatives. On methanesulfonylation and p-toluenesulfonylation, the hexakis(2,3-di-O-acetyl) derivative 16 afforded the hexakis(2,3-di-O-acetyl-6-O-methylsulfonyl 17 and 2,3-di-O-acetyl-6-O-p -tolylsulfonyl 18) derivatives, respectively. Nucleophilic displacement of 17 and 18 with iodide, bromide, chloride, and azide ions afforded the hexakis(6-deoxy-6-iodo 19, 6-bromo-6-deoxy, 6-chloro-6-deoxy, and 6-azido-6-deoxy) derivatives, respectively, of α-cyclodextrin dodeca-acetate. The hexakis (2, 3-di-O-acetyl-6-deoxy) derivative was prepared from 19. Selective glucosylation of 16 with 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl bromide under catalysis by halide ion, followed by removal of protecting groups, furnished 6-O-α-D-glucopyranosyl-α-cyclodextrin.     

Synthesis of N-Demethyl-N-Substituted-14-Hydroxycodeine and Morphine Derivatives+

A fews representatives (1b-d) of a novel group of structurally related morphine-antagonist compounds have been prepared in stereochemically homogeneous form. The employed procedures involve O-demethylation either of the corresponding codeine derivatives 2b-d, or those of the N-alkylated analogues 2b-c synthesized from N-demethylthebaine (7a) by means of N-alkylation and subsequent transformations of 7b, d–compounds selected from the resulting functionalized thebaines 7b-exs.     

Special Report Chemical Sensors for In Vivo Monitoring: Clinical Aspects

Abstract

The origins and purpose of a new European Community Concerted Action on “Chemical Sensors for In Vivo Monitoring” are described: the overall aim is to promote the development and application of chemical sensors for in vivo monitoring. A report is presented on the first Workshop Meeting entitled “Clinical Aspects of In Vivo Sensing”, which addressed the question of the analyte to be sensed, specific and general problems of in vivo sensing, and future prospects.     

Synthesis of 4-O-(α-L-Rhamnopyranosyl-D-Glucopyranuronic Acid

Abstract

Two approaches were used for the synthesis of 4-O-(α-l-rhamno-pyranosyl)-d-glucopyranuronic acid (1). Rhamnosylation of benzyl 6-O-allyl-2,3-di-O-benzyl-β-d-glucopyranoside (7), followed by deallylation, oxidation to uronic acid, and deblocking afforded 1. Alternatively, rhamnosylation of suitably protected d-glucuronic acid derivatives (25 and 26) gave the protected pseudoaldoBiouronic acid derivatives (19 and 30), which were deprotected. Rhamnosylations were performed in high stereoselectivity without neighbouring-group assistance using 2,3,4-tri-O-benzyl-1-O-trichloroacetimidoyl-α-l-rharnnopyranose (27) with tri-fluoromethanesulfonic acid catalysis.     

Intramolecular Oxidative Coupling of the Bis Enolate Derived from Dimethyl β,β-Dimethylglutarate: A Facile Stereoselective Route to a Versatile Synthon for Preparation of Insecticidal Pyrethroids

Treatment of the bis enolate derived from dimethyl β,β-dimethylglutarate with silver chloride afforded dimethyl cis-3,3-dimethyl-1,2-cyclopropanedicarboxylate, a versatile synthon for the preparation of the acid component of cis-pyrethroids. A similar experiment utilizing iodine as the oxidant led to the isolation of the corresponding trans diester with good stereo-selectivity.     

Reactions of Cyclic Anhydrides XIV. Facile Syntheses of Fused Heterocycles via Anilic Acids Pyridobenzoxazinones,Isoquinolinobenzoxazinones and Isocoumarinoquinolines

o-Carboxyhomomaleanilic acids (5) and o-carboxyhomophthalanilic acids (6) on treatment with sodium acetate-acetic anhydride furnished pyridobenzoxazinones (8) and isoquinolinobenzoxazinones (9) respectively in quantitative yields. Conversion of o-formylhomophthalanilic acid (7) to isocoumarinoquinoline (11) via 2-axo-3(o-carboxyphenyl)quinoline (10) is also described.     

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.