An Improved Asymmetric Synthesis of Unusual Amino Acid (2S,3S)‐3‐Hydroxyproline

Abstract

An improved three‐steps method for the conversion of N‐benzyl (S)‐3‐hydroxypyrrolidin‐2‐one 6 to (2S,3S)‐3‐hydroxyproline 1 is reported. The key step is the reductive cyanation of 6. The synthesis of 1 constitutes a formal asymmetric synthesis of (2S,3S)‐3‐hydroxyproline betaines 2.     

Facile Synthesis of (S,S)‐1,2‐Diacylamides and (S,S)‐1,2‐Diamines with C 2‐Symmetry

A series of chiral vicinal tertiary diacylamides with C ₂‐symmetry was synthesized from (S)‐α‐phenylethylamine, different aromatic aldehydes, and oxalyl chloride. The diacylamides obtained were then reduced to afford chiral vicinal diamines with C ₂‐symmetry. We propose that the diacylamides existed in four stable conformational isomers in solution because of the dihedral angle between acylamide bonds.     

Regioselective Endocyclic Oxidation of Enantiopure 3‐Alkylpiperidines: Synthesis of (3S,5S)‐(‐)‐3‐Ethyl‐5‐Methylpiperidine

An efficient regioselective endocyclic oxidation of enantiopure 3‐alkylpiperidines 1(a–c) with bromine in acetic acid to generate the corresponding 5‐alkylpiperidin‐2‐ones 3(a–c) as main product is described. In addition, starting from 3a or 3b, the synthesis of (3S,5S)‐(‐)‐3‐ethyl‐5‐methylpiperidine 6 · HCl was achieved. Finally, the X‐ray single‐crystal analysis of compound 4 is reported.     

Simple and Advantageneous Stereoselective Synthesis of (Z)-Allyl Phosphonates Starting from Baylis–Hillman Adducts

Baylis–Hillman adducts 3-hydroxyl-2-methylene alkanoates have been converted in one pot into the corresponding (Z)-allyl phosphonates by treatment with FeCl₃ and trialkyl phosphites in toluene under reflux. The products are formed in excellent yields (88–98%) within 1–1.5 h. The process is highly convenient and efficient, cost-effective, and remarkably stereoselective.     

Synthesis of C‐Nucleoside Analogues Starting from 1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one

Abstract

1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one (4) was synthesized by the reaction of (methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)ethanal (2) with lithium phenylethynide and following oxidation. Compound 4 and hydrazine hydrate provided the 3(5)‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl‐methyl)‐5(3)‐phenyl‐1H‐pyrazole (5). The reactions of 4 with amidinium salts and a S‐methyl‐isothiouronium salt, respectively, furnished the pyrimidine C‐nucleoside analogues 6a–6c. Treatment of 4 with 2‐aminobenzimidazole afforded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐ylmethyl)‐4‐phenyl‐benzo [4,5]imidazo[1,2‐a]pyrimidine (7a). Compound 4 and sodium azide yielded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐1‐[5(4)‐phenyl‐1H(2H)‐1,2,3‐triazole‐4(5)‐yl]ethanone (8).     

Liquid‐Phase Synthesis of Methyl (E)‐2‐Nitromethyl‐2‐alkenoates Based on PEG‐Supported α‐Phenylselenopropionate

The reaction of the lithio derivative of novel polyethylene glycol (PEG)‐supported α‐phenylselenopropionate with aldehydes, followed by oxidation–elimination with 30% hydrogen peroxide and then treatment with sodium nitrite, formed PEG‐bound 2‐nitromethyl‐2‐alkenoates. Subsequent cleavage from the PEG efficiently afforded methyl (E)‐2‐nitromethyl‐2‐alkenoates in good yields and high purities.     

Facile One‐Pot Synthesis of 3,4‐Dihydropyrimidin‐2(1H)‐one Catalyzed by Zn(NH2SO3)2

An efficient synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones (DHPMS) from aromatic aldehydes, β‐keto ester, and urea (or thiourea) in refluxing ethanol using zinc sulfamate as a catalyst is first described here. Compared to the classical Biginelli reaction, this new method consistently has the advantages of good yields (76–96%), short reaction time (2–5 h), no corrosion of equipment, ease of manipulation, and low‐cost catalyst.     

Facile Method for Stereoselective Synthesis of New Chiral (1R,4aR,8aR)‐1,3,4,4a,5,7,8,8a‐Octahydro‐2‐methylene‐naphthalene‐6‐one‐1‐propanenitrile,an Important Precursor of Solanapyrones

A novel and facile strategy for stereoselective synthesis of new chiral (1R,4aR,8aR)‐1,3,4,4a,5,7,8,8a‐octahydro‐2‐methylenenaphthalene‐6‐one‐1‐propanenitrile (8) by one‐pot stereoselective hydrogenation/acetalization and Beckmann fragmentation is described. Chiral octalone 8, an important precursor of solanapyrone, was obtained in good yield.     

Solid-Phase Stereoselective Synthesis of (E)-1, 2-Disubstituted Ethenes from Polymer-Sopported a-Selenoaldehydes

Reaction of polymer-supported a-selenoaldehydes with Grignard reagents afforded polymer-bound B-hydroxyalkyl selenides, which treated with thionyl chloride and triethylamine leading to (E)-1, 2-disubstituted ethenes in good yield.     

Stereoselective Synthesis of β‐Lactams by Using D‐Mannitol‐Derived Oxazolidin‐2‐one as a Chiral Auxiliary

Abstract

Chiral oxazolidin‐2‐ones containing isopropylidene and cyclohexylidene functionalities, readily available from D‐mannitol, have been demonstrated to undergo highly diastereoselective β‐lactam synthesis via the Staudinger reaction with Mukaiyama reagent. Stereoselectivity for cis‐β‐lactam was the result of the [2?+?2] cycloaddition reaction of ketene to trans imines, and cyclohexylidene showed better yield and stereoselectivity than the isopropylidene auxiliary.     

Stereoselective Synthesis of [2S,3R]-β-Hydroxy Ornithine

(2S,3R)-threo-β-hydroxy ornithine has been synthesized in a stereoselective manner by the C₂ opening of epoxyalcohol 9 with benzyl isocyanate.

     

Asymmetric Synthesis of (2S)‐1‐(3,4‐Dihydroxyphenoxy)‐3‐(3,′4′‐Dimethoxyphenoxy) Ethylamino‐2‐propanol hydrochloride (RO363)

Enantiomerically pure (S)‐RO363 was synthesized by using (R,R) Salen Co(III) complex for the resolution of terminal epoxide. The hydrolytic kinetic resolution process was carried out at room temperature in excellent enantioselectivity. The method can be applied for large‐scale preparation of (S) RO363.     

Synthesis and ferroelectric properties of chiral liquid crystals derived from (S)‐1‐propyloxy‐2‐propanol

A new optically active chiral moiety, (S)‐1‐propyloxy‐2‐propanol, was designed and synthesized by the treatment of 1‐propanol with (S)‐propylene oxide under basic conditions. Its derivatives, the (R)‐1‐propyloxy‐2‐propyl 4‐[4‐(4‐alkoxyphenyl)phenoyloxy]benzoates, PPmPPB (m = 8–12), were prepared for the investigation of mesomorphic properties. All of the chiral materials displayed enantiotropic SmA? and SmC? phases, and the shorter alkyl chain members (m = 8–11) displayed an additional unidentified SmX? phase. The switching current, spontaneous polarization, tilt angle, dielectric constant and electro‐optical response for the materials in the ferroelectric SmC? phase were measured. The electro‐optic responses in polyimide film‐coated homogeneously aligned cells exhibit thresholdless, V‐shaped switching in the ferroelectric phase.     

Alternative,High‐Yield Synthesis of (E)‐4‐Oxonon‐2‐enoic Acid from 2‐Methoxyfuran

Alkylation of 2‐methoxyfuran, followed by in situ TPP‐sensitized photooxygenation of 2‐methoxy‐5‐pentylfuran in the presence of Me₂S, gave methyl (Z)‐4‐oxonon‐2‐enoate. Hydrolysis of methyl (Z)‐4‐oxonon‐2‐enoate afforded (E)‐4‐oxonon‐2‐enoic acid in three steps and in 79% overall yield.     

Stereoselective Synthesis of (2E, 6E, 10E)‐ Geranylgeraniol from Geranyllinalyl Acetate via Palladium‐Catalyzed Amination

Amination of geranyllinalyl acetate 1 with diethylamine and Pd(OAc)₂ · 2PPh₃ as catalyst gave N,N‐diethylgeranylgeranylamine 3 (E/Z=91/9) in 85% yield. Amine 3 was treated by ethyl chloroformate followed by KOAc to give geranylgeranyl acetate 2 in 82% yield. Then 2 was hydrolyzed to afford geranylgeraniol 4 in 94% yield.     

Synthesis of 3β,3β,5‐tribromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one by Bromination of Dehydroacetic Acid

Abstract

Bromination of dehydroacetic acid giving rise to 3β,3β,5‐tribromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one is described.     

Synthesis,Characterization and Photocrosslinking Properties of Poly(1‐(4‐Methacrylamidophenyl)‐1‐(4‐nitrophenyl)prop‐1‐en‐3‐one)

The phenylmethacrylamide monomer, 1‐(4‐methacrylamidophenyl)‐1‐(4‐nitrophenyl)prop‐1‐en‐3‐one (MPNP) containing a photosensitive group was synthesized by reacting 4‐nitrocinnamoylaniline with methacryloyl chloride in the presence of triethylamine at 0–5°C. The functional monomer, MPNP was polymerized in ethyl methyl ketone (EMK) under nitrogen atmosphere at 70°C using benzoyl peroxide (BPO) as the initiator. The synthesized polymer was characterized by UV, IR, ¹H‐NMR and ¹³C‐NMR spectroscopy. The molecular weight data of the polymer as obtained from gel permeation chromatography suggests a higher tendency for chain termination by radical recombination than disproportionation. The thermal studies of the polymer were obtained from thermogravimetric analysis. The glass transition temperature of the polymer was determined by differential scanning calorimetry. The solubility of the polymer was tested in various organic solvents at room temperature. The photosensitivity of the polymer was investigated in various solvents in the presence and absence of triplet photosensitizers. The effect of the different solvents nature and concentration on the rate of photocrosslinking of the polymer were also examined for using the polymer as negative photoresist materials.     

Synthesis,Structures and Properties of Polyimide Based on 2,2′‐Bis(4‐aminophenoxy phenyl) Propane

2,2‐Bis[4‐(4‐aminophenoxy)phenyl] propane (BAPP), as a monomer to prepare polyimide, was synthesized from Bisphenol A and p‐chloronitrobenzene via the nucleophilic substitution reaction. The structures of the diamine monomer BAPP and an intermediate dinitrocompound 2,2′‐bis(4‐nitrophenoxy phenyl) propane (BNPP) were confirmed by FTIR and NMR. A novel polyimide was derived from BAPP and 3,3′,4,4′‐oxydiphthalic dianhydride (ODPA) in DMAc by a two‐step method. FTIR, DSC, TGA, and DMA were employed to characterize the precursor and the polyimide. The glass transition temperature of the polyimide was about 225–230°C. The measurement of mechanical properties indicated that the polyimide exhibited a typical yield behavior of thermoplastic polymers, which is very different from other polyimides. The elongation at break of the polyamic acid and polyimide was 6% and 29%, respectively.     

Synthesis of Insecticidally Active 3-Phenoxy Benzyl and α (RS) Cyano-3-Phenoxy Benzyl (±) Trans 2-(2, 2-Dichlorovinyl) Spiro (2,5)-Octane-1-Carboxylates

Cyclopropane carboxylic acid esters, possessing spirofused cycloallcyl rings, in place of the conven- tional gem-dimethyl group of natural pyrethrins and synthetic pyrethroids also exhibit good insecticidal I activity against a wide range of insect species. In addition, these compounds exhibit knock-down activity on flying insects. Someoc-cyan0-3-phenoxy benzyl esters of (±) - cis and (±) trans 2-(2,2-dichlorovinyl)-spiro (2,5)-octane-l-carboxylic acid and the lower spiro cycloalkyl members of the homologous series, have been synthesised and found to be active against, musca domestica, cotton leafworm etc, with good knock-down effect. The acid moieties of the above esters have been synthesised by reaction of alkyl diazo acetates on suitably substituted olefins 2, 3.     

Amino Acids as a Chiral Pool: Synthesis of (S)‐and (R)‐2‐N‐Carbomethoxy‐5‐aminoindane from (S)‐ and (R)‐Phenylalanines

Enantioselective syntheses of (R)‐and (S)‐2‐N‐carbomethoxy‐5‐aminoindanes from (R)‐ and (S)‐phenylalanines, respectively, are described. A Friedel–Crafts reaction employing N‐carbomethoxy phenylalanine leads to chiral 2‐N‐carbomethoxy‐1‐indanone, which is diastereoselectively reduced to 1‐hydroxy‐2‐N‐carbomethoxyindane. After protection of the hydroxyl group, a regioselective nitration gives a 6‐nitroindane intermediate, which upon hydrogenation affords (R)‐or (S)‐2‐N‐carbomethoxy‐5‐aminoindane.