An Efficient Synthesis of α-Bromoacetals via a Combined Chemical and Electrochemical Bromination

α-Bromoacetals (1) are valuable precursors in synthesis of α,β-unsaturated carbonyl compounds (2), 1-alkoxybutadienes² (3), ketene acetals³ (4), 2-methoxyallyl bromides⁴ (5) and other compounds. Because of our interest in the chemistry^5,6 of 3 and 4 we attempted to improve known procedures for the preparation of 1 with the aim to get a short and efficient synthesis of these compounds.     

New Synthesis of α-Bromo-α,β-Unsaturated Esters

A synthesis of α-bromo-α,β-unsaturated esters 2 from tert-butyl α-(trimethylsilyl)-α-bromoacetate (1) and carbonyl compounds is described.     

Efficient purification and complete NMR characterization of galactinol,sucrose, raffinose,and stachyose isolated from Pinus halepensis (Aleppo pine) seeds using acetylation procedure

The use of precipitation followed by acetylation procedures and preparative TLC purification allowed a facile isolation of four carbohydrates from the methanol extract of Pinus halepensis seeds. The isolated oligosaccharides exhibited high degree of purity. They were identified as α-D-galactosyl-(1→1)-myo-inositol nonaacetate (1), α-D-glucosyl-(1→2)-β-D-fructosyl octaacetate (2), α-D-galactosyl-(1→6)-α-D-glucosyl-(1→2)-β-D-frutosyl undecaacetate (3), and α-D-galactosyl-(1→6)-α-D-galactosyl-(1→6)-α-D-glucosyl-(1→2)-β-D-frutosyl tetradecaacetate (4) and were isolated for the first time from this plant. The ¹H and ¹³C NMR assignments for compounds 2, 3, and 4 were detailed herein for the first time.     

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.     

Asymmetric Synthesis of Aryl 2-Piperidyl Methanols from a Chiral α-Aminonitrile Precursor

Synthesis of enantiomerically pure phenyl 2-piperidyl methanols from a convenient chiral α-aminonitrile 1 is described. Reaction with aldehydes of the anion generated from 1 leads to threo (αR, 2R) products, whereas treatment of 1 with organolithium reagents affords erythro (αR, 2S) compounds.     

Reaction of Aziridinones with 2-Lithio-1, 3-Dithiane: Selective Cleavage of the Aziridinone Ring

The reaction of aziridinones (1a-1d) with tert-butyllithium at room temperature affords α-hydroxy imines (5ax-5dx).¹ One possible pathway leading to these products involves the formation of 2 as an intermediate, followed by rearrangement to 3. In fact, under carefully controlled conditions that prevent the rearrange-of 2 to 3, α-amino ketones (4ax-4dx), which arise from the protonation of 2, can be isolated. Other α-amino ketones were synthesized in a like manner from aziridinones by treatment with a variety of alkyllithium reagents.² Baumgarten and co-workers³ subsequently reported similar products from the reaction of phenyllithium and methyllithium with an aziridinone. In an attempt to extend this study to other organolithium reagents, especially those bearing functional groups, we have investigated the reaction of     

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.     

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.     

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.     

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.     

First Stereqselective Synthesis of Nitrophenyl 2-Deoxy- β-D-glycosides

α-Dithiophosphates of peracetylated 2-deoxyhexc-pyranoses, 1a, 1b and 2, uhich are easily prepared by addition of organic phosphorodithioic acids to glycais react smoothly with resin-bound 2- and 4-nitrophenoxides to give stereoselectively the respective nitrophenyl 2-deoxy-β-D-hexopyranosides (3, 4, 5 and 6) in high yields. Glycosylation of the 2, 4-dinitro'phenoxide, however, leads with comparable stereoselectivity to 2,4-dinitrophenyl 2-deoxy- α-D-hexopyranosides (7 and 8).

Glycosides 3 - 6 are quantitatively deacetylatec by Amberlyst A-26 (OH^-), whereas glycosides 7 and 8, under the same reaction conditions undergo splitting of the O-glycosidic bond.     

Syntheses of 4, 5-Di-O-bexzyl-2-deoxy-2-C-methyl L-lyxose and Methyl 4, 5-Di-O-bexzyl-2-deoxy-2-C-methyl-3-O-metkyl-L-lyxonate

The title compounds, which possess C-methyl groups at the α-position of carbonyl groups and vicinal hydroxyl groups with syn (three) relationship, were synthesized efficiently from known 3-decxy-1, 2-O-isopropylidene-3-C-methyl-α-D-allofuranose. The synthetic routes involve: 1) inversion of C-5 configuration of the starting sugar, 2) suitable protection of the 5, 6-diol, and 3) glycol cleavage of the 1, 2-diol to an aldehyde or direct oxidation of the diol to carboxylic acid.     

Synthesis of (3-Ethoxycarbonyl But-3-en-2-yl)phenyl Sulfone and (2-Ethoxycarbonyl But-2-en-1-yl)phenyl Sulfone from Ethyl 2-Bromomethyl But-2-enoate

The synthetic usefullness of “acrylic” tin compounds has been largely demonstrated by BALDWIN and coworkers¹. We wanted to apply this methodology to prepare the peroxide precursors. Thus, we needed to synthesize (2-ethoxycarbonyl prop-2-enyl) phenyl sulfone 1, (2-ethoxycarbonyl but-2-en-1-yl) phenyl sulfone 2 and (3-ethoxycarbonyl but-3-en-2-yl) phenyl sulfone 3. We wish to report the synthesis of such compounds using the advantage of the complexing effect of Polyethyleneoxide 400 (PEO 400) on alkali cations. We also must to report the isomerisation of 2 to 3 in presence of traces of sodium sulfinate which make access to 2 difficult.     

Synthesis of 2-Carbamoyl-2-Deoxy Glycosides

Abstract

Recently we have reported the addition of trichloracetyl isocuyanate to glycals 1 _1,2,3. The reaction led to the highly stereoselective formation of a mixture of unstable [2+2] and [4+2] cycloadducts 2 and 3. The isocyanate adds to the glycal moiety anti to the substituent at C-3. The addition of benzylamine to the reac6tion mixture led to N-deprotection of 2 and allowed us to isolate stable bicyclic β-lactams 4 _1-3. We have shown also that 2 (a mixture of α-L-gluco and β-L-manno isomers) obtained from L-rhamnal 1 (R¹[dbnd]Ac, R²[dbnd]CH₃ under high pressure, when treated with methanol, underwent a rapid trans opening of the four-membered ring to give respective glycosides 5(β-L-gluco and α-L-manno isomers). On the other hand 3 (R¹[dbnd]Ac, R²[dbnd]CH₃) under the same conditions added a molecule of methanol to the C[dbnd]N double bond affording 6.     

1,1-DIANIONS OF ALKYL PHENYL SULPHONES AS SYNTHETIC INTERMEDIATES IN CYCLIZATION REACTIONS

Abstract

α-Sulphonyl carbanions are known to be good nucleophiles both in intermolecular and in intramolecular reactions¹. In the same way gem-dimetalloderivatives of alkyl phenyl sulphones I a,b readily add to aldehydes and ketones to give the (β-hydroxy compounds II in the case of dilithioderivatives Ia, while from dimagnesioderivatives Ib α, β-unsaturated sulphones III are also obtained².     

The Synthesis of Substituted α, β-Butenolides from γ-Hydroxy-α, β-Acetylenic Esters

Abstract

The α, β-butenolide ring system is found in a number of physiologically important natural products² and there has been recent interest in the development of methods of synthesis of compounds of this type.³ It is well known that α, β-unsubstituted butenolides may be prepared by catalytic hydrogenation of γ-hydroxy acetylenic acids.^4,5b Recently, an excellent route of γ-hydroxy acetylenic esters which involves the addition of the lithium acetylide salts of propiolic esters to aldehydes⁵ and ketones⁶ has become available. We have carried out the addition of ethyl lithiopropiolate (1) to cyclohexanone (2) and 4-t-butylcyclohexanone (3) and wish to report the conversion of these adducts into corresponding β-methyl or β-methyl-α-allyl-α, β-butenolides.     

Halogenotropy in Phosphorus-Carbon Diad

Abstract

NMR and chemical studies have shown that α-halogenoalkyl-phosphines 1 and P-halogenoylids 2 exist as halogenotropic tautoineric systems. The position of the equilibrium depends on the used solvent, temperatures and substituents at the α-carbon atom. For example, the equilibrium 1 2 shifts towards the phosphine from 1 if the substituents at the α-carbon atom are electron-donating (R = H, Me, Pr, i-Pr). These compunds, existing preferably in the phosphine form, undergo typical reactions both for tervalent phosphorus compounds and P-halogenoylids. Tervalent phosphorus compounds, α-halogenoalkylphosphines 1 add sulfur and react with anhydrous HCl to convert into the dichlorophosphines -4. Like the P-halogenoylids, they add alcohols and phenols forming the phosphonium salts 5, 6, react with primary amines and aniline to yield the iminophosphonates 7 They also form the 2-halogenoalkylphosphonates 8 in the reaction with aldehydes.     

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     

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.     

Synthesis of Acylacetylenes from α-Diazo-β-Hydroxylcarbonyl Compounds

A facile synthesis of α-diazo-β-hydroxy ketones and esters by the condensation of aldehydes or ketones with acyldiazomethanes was reported recently.² Exposure of the trifunctional compounds to boron trifluoride in ether-acetonitrile solution leads to acylacetylenes. Thus substances 1 and 3 were converted readily into acetylenes 2 and 4 respectively.³ This makes available a simple two-step procedure for the synthesis of conjugated acetylenic carbonyl compounds.