Copper(I)‐Catalysed Multicomponent Reaction: Straightforward Access to 5‐Hydroxy‐1H‐pyrrol‐2(5H)‐ones

A copper‐catalysed multicomponent coupling reaction between readily available (Z)‐3‐iodoacrylic acids, terminal alkynes, and primary amines was developed to smoothly access a small library of 5‐hydroxy‐1H‐pyrrol‐2(5H)‐ones in good yields. This practical and general process was applied to a short‐steps synthesis of the natural product pulchellalactam.

     

Synthesis of biodegradable polyurethanes chain‐extended with (2S)‐bis(2‐hydroxypropyl) 2‐aminopentane dioate

Polyurethanes (PUs) are the most widely used polymers because of their biocompatibility, tunable mechanical properties, and chemical versatility. In this study, a two‐step condensation polymerization of polycaprolactone diol and hexamethylene diisocyanate was carried out, and a glutamic acid ester derivative, (2S)‐bis(2‐hydroxypropyl) 2‐aminopentane dioate (HPAP), was used as a new chain extender to accelerate the biodegradation properties of PU. HPAP was synthesized by the Fischer esterification of l ‐glutamic acid. The chemical structure of HPAP was confirmed by high‐resolution mass spectroscopy and m/z (EI) was found to be 264.1447 [calculated value = 264.1443 for C₁₁H₂₁NO₆ (M⁺)]. The Berry plot of static light‐scattering measurements showed that PU–HPAP had a weight‐average molecular weight and radius of gyration of 33,100 g/mol and 1420 nm, respectively. The presence of HPAP in the PU structure facilitated hydrogen bonding between the polymer chains and increased the glass‐transition temperature from ?56 °C (PU) to ?50 °C (PU–HPAP). PU–HPAP showed the highest hydrophilicity and surface free energy among all of samples, and this accelerated the in vitro biodegradation period via surface erosion. In addition, PU–HPAP did not show any cytotoxic effects on the L929 cells. A new biodegradable and biocompatible PU–HPAP was obtained as candidate for tissue engineering applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45764.     

Optically Active 4‐Substituted (S)‐2‐Phenyl‐2‐oxazolines

(R)‐4‐Hydroxymethyl‐2‐phenyl‐2‐oxazoline (R)‐ 1 ) was prepared from (L)‐serine. The respective tosylate ((S)‐ 2 ) was converted into sulfides (S)‐ 4 and (S)‐ 5 , and sulfone (S)‐ 6 , useful starting materials for the elaboration of additional chiral centers. A previously reported [ α]_D ²⁵ value for (R)‐ 4 is corrected.     

Rhodium(I)‐Catalyzed Diastereoselective Cycloisomerization of Enynes with Tethered (S)‐2‐Methyl‐2‐propanesulfinyl Imine

The rhodium(I)‐catalyzed cycloisomerization of enynes with tethered (S)‐2‐methyl‐2‐propanesulfinyl imine affords 5‐ or 6‐membered cyclic compounds containing exocyclic 1,3‐diene moieties in a stereoselective manner. The reaction proceeds through β‐hydride elimination of a 7‐membered azarhodacycle intermediate, which is generated from three unsaturated bonds (i.e., alkene, alkyne, and CN bonds) and an Rh(I) complex. The resultant cyclic compounds could be reacted with various dienophiles to afford spiroamides as single isomers through the Diels–Alder reaction.

     

A Catalytic Deprotection of S,S‐, S,O‐ and O,O‐Acetals Using Bi(NO3)3⋅5 H2O under Air

S,S‐Acetals are smoothly deprotected with air in the presence of a catalytic amount of Bi(NO₃)₃⋅5 H₂O (1–50 mol %) under ambient conditions to regenerate the original carbonyl compounds in good to excellent yield. This mild, simple, and environmentally benign system is successfully applied to the deprotection of S,O‐ and O,O‐acetals and is compatible with various functional groups. From the mechanistic study of the reaction, the catalytic cycle is considered to be composed of the following four steps: (1) the nitrososulfonium ion of the S,S‐acetal is formed by attack of nitrosonium ion (NO ⁺) generated from Bi(NO₃)₃⋅5 H₂O through the equilibrium with NO₂, (2) the nitrososulfonium ion is hydrolyzed to afford the hemithioacetal and thionitrite, (3) the hemithioacetal collapses to the original carbonyl compound and thiol, which is oxidized by NO ⁺ to give disulfide and NO via thionitrite, and (4) the NO captures molecular oxygen from air to regenerate NO₂.     

P[CF3(CF2)5CH2MA‐co‐MMA] and P[CF3(CF2)5CH2MA‐co‐BA] copolymers: Reactivity ratios and surface properties

This study aimed at reducing the surface energy of coatings by copolymerization of commonly used monomers with fluorine‐containing monomers. Copolymers of 1,1‐dihydroperfluoroheptyl methacrylate (FHMA) and methyl methacrylate (MMA) or butyl acrylate (BA) are prepared by low‐conversion polymerization in solution. Using ¹H‐NMR data and nonlinear least‐squares data fitting, reactivity ratios of these systems at 80°C are determined to be r_FHMA = 1.31, r_MMA = 0.76, and r_FHMA = 3.15, r_BA = 0.38, respectively. We assume that the penultimate unit effect plays an important role in these systems. Introduction of the perfluoroalkyl side chain lowers the polymer surface energy significantly; copolymers of MMA and FHMA show a reduction in total surface energy of about 50 % at a content of 15 mol % FHMA as compared with pure PMMA. The attainable reduction in surface energy is much larger than with, for example, Teflon. This is due to the preferential adsorption of the —CF₃ groups of the fluoroalkyl side chain, if compared to that of the —CF₂— groups of Teflon. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 159–165, 2001     

Synthesis of 4‐Aryl‐2(5H)‐furanones by Gold(I)‐Catalyzed Intramolecular Annulation

A novel method that involves intramolecular annulation and a new type of rearrangement has been developed for the synthesis of 4‐aryl‐2(5H)‐furanones. A variety of prop‐2‐ynyl 3‐oxo‐3‐phenylpropanoates undergo annulation cyclization in the presence of chloro(triphenylphosphine)gold and trifluoromethanesulfonic to afford the desired products in moderate to high yields.     

Efficient Biosynthesis of (R)‐ or (S)‐2‐Hydroxybutyrate from l‐Threonine through a Synthetic Biology Approach

An efficient multi‐enzyme cascade reaction for the synthesis of (R)‐ or (S)‐2‐hydroxybutyric acid [(R)‐ or (S)‐2‐HB] from l ‐threonine was developed by using recombinant Escherichia coli cells expressing separately or co‐expressing l ‐threonine deaminase from Escherichia coli K‐12 (ilvA), formate dehydrogenase (FDH) from Candida boidinii and l ‐lactate dehydrogenase (l ‐LDH) from Oryctolagus cuniculus or d ‐lactate dehydrogenase (d ‐LDH) from Staphylococcus epidermidis ATCC 12228. Up to 750 mM of l ‐threonine were completely transformed to (R)‐ or (S)‐2‐HB in optically pure form (>99% ee) with high isolated yields. This one‐pot multi‐enzyme transformation provides a new practical method for the synthesis of these important optically pure compounds.

     

Morphology of the transparent IPN‐like system PE: (BMA‐co‐S)

In the study of interpenetrating polymer networks (IPN)‐like systems consisting of polyethylene (PE) and butyl methacrylate (BMA)–styrene (S) copolymer PE/(BMA‐co‐S), the effect of the crosslinker on the morphology of IPN by using electron microscopy and atomic force microscopy (AFM) was investigated. The IPN‐like system PE/(BMA‐co‐S) represents a two‐phase system with finely dispersed domains of crosslinked PE matrix. The interphase between dispersed domains and PE matrix is inhomogeneous and is considered the most interpenetrated part of this IPN‐like system. The size of the domains decreases with the content of crosslinker used. The AFM micrographs allowed the observation of PE lamellae with lengths of about 25 nm. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 2615–2620, 2001     

Stabilization of Telomeric I‐Motif Structures by (2′S)‐2′‐Deoxy‐2′‐C‐Methylcytidine Residues

G‐quadruplexes and i‐motifs are tetraplex structures present in telomeres and the promoter regions of oncogenes. The possibility of producing nanodevices with pH‐sensitive functions has triggered interest in modified oligonucleotides with improved structural properties. We synthesized C‐rich oligonucleotides carrying conformationally restricted (2′S)‐2′‐deoxy‐2′‐C‐methyl‐cytidine units. The effect of this modified nucleoside on the stability of intramolecular i‐motifs from the vertebrate telomere was investigated by UV, CD, and NMR spectroscopy. The replacement of selected positions of the C‐core with C‐modified residues induced the formation of stable intercalated tetraplexes at near‐neutral pH. This study demonstrates the possibility of enhancing the stability of the i‐motif by chemical modification.     

Synthesis and Derivatization of Substituted (R)‐ and (S)‐ C‐Allylglycines

Various (R)‐ and (S)‐C‐allylglycine derivatives were synthesized by means of an auxiliary controlled diastereoselective aza‐Claisen rearrangement. Starting from (S)‐configured auxiliaries derived from optically active proline, an aza‐Claisen rearrangement enabled us to synthesize α(R)‐configured γ,δ‐unsaturated amides. Since (R)‐allylglycine derivatives could be directly generated by reacting N‐allylproline derivatives and various protected glycine fluorides, the corresponding (S)‐enantiomers were built‐up via an initial α‐chloroacetyl chloride rearrangement and a subsequent chloride azide substitution with complete inversion of the configuration. High diastereoselectivities were obtained (>15 : 1). The auxiliary could be efficiently removed by organolithium reactions of the amides furnishing α‐amino ketones. Another allyllithium addition allowed us to introduce a second allyl chain with high diastereoselectivity. Final ring closures by means of metatheses using Grubbs' (I) catalyst gave raise to the formation of enantiopure phenanthridines and cyclohexenes displaying defined substitution patterns ready for alkaloid total syntheses.     

(R/S)‐BINOL‐α‐Phosphoryloxy Enecarbamate‐Mediated and (R/S)‐Titanium(IV) BINOLates‐Catalyzed Enantioselective Intramolecular Heck/Aza‐Diels–Alder Cycloaddition (IHADA): An Expedient Methodology

An (R/S)‐titanium(IV) BINOLate‐catalyzed highly enantioselective intramolecular Heck/aza‐Diels–Alder cycloaddition (IHADA) cascade was developed to prepare tetrahydropyridoindoles (tHPs) and octahydropyrazinopyridoindoles (oHPPs) from in situ generated (R/S)‐BINOL α‐phosphoryloxy carbamate ( αPPC2 ) in one pot. Chiral cooperativity between (R/S)‐αPPC2 and (R/S)‐titanium(IV) BINOLate was observed and successfully utilized for the construction of various tHPs (7 examples) and oHPPs (17 examples).

     

Synthesis,characterization, and thermal degradation of novel poly(2‐(5‐bromo benzofuran‐2‐yl)‐2‐oxoethyl methacrylate)

A novel methacrylate monomer containing benzofuran side group, 2‐(5‐bromo benzofuran‐2‐yl)‐2‐oxoethyl methacrylate (BOEMA), was synthesized from esterification reaction of 2‐bromo‐1‐(5‐bromo benzofuran‐2‐yl) ethanone with sodium methacrylate at 85°C in the presence of 1,4‐dioxane solvent. After characterization with Fourier transform infrared spectrophotometer, nuclear magnetic resonance (¹H‐NMR and ¹³C‐NMR), its homopolymerization was carried out by free radical polymerization at 60°C in the presence of benzoyl peroxide initiator and 1,4‐dioxane solvent. The glass transition temperature (T_g) of the synthesized novel polymer, poly(2‐(5‐bromo benzofuran‐2‐yl)‐2‐oxoethyl methacrylate) [poly(BOEMA)], was determined to be 137°C with differential scanning calorimetry technique. Thermal degradation kinetics of poly(BOEMA) was investigated by thermogravimetric analysis method at different heating rates with 5°C/min intervals between measurements. From dynamic measurements, the analysis of each process mechanism of Coats–Redfern and Van Krevelen methods showed that the most probable model for the decomposition process of poly(BOEMA) homopolymer agrees with the random nucleation, F₁ mechanism. The apparent decomposition activation energies of poly(BOEMA) by Kissinger's and Flynn–Wall–Ozawa methods in the studied conversion range were 188.47 and 180.13 kJ/mol, respectively. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers     

Intumescence in poly(butylene terephthalate): the effect of 2‐methyl‐1,2‐oxaphospholan‐5‐one 2‐oxide and ammonium polyphosphate

The flame‐retardant effect of 2‐methyl‐1,2‐oxaphospholan‐5‐one 2‐oxide (OP) and ammonium polyphosphate (APP) in poly(butylene terephthalate) (PBT) was studied by the limiting oxygen index and the UL94 test. A self‐extinguishing formulation (V‐0 rating) was achieved by the addition of 15 wt% APP and 10 wt% OP. The fire‐retardant effect was attributed to the condensed‐phase mechanism of intumescence. Mechanistic studies were performed using thermogravimetry, IR characterization of solid residues and GC–MS characterization of the gaseous and high‐boiling products. OP–APP was shown to cause ammonolysis of PBT, formation of aromatic nitriles in the high‐boiling products and phosphorus ester groups and polyphosphoric acid–phosphorus pentaoxide in the solid residue. Copyright © 2003 Society of Chemical Industry     

Stereocontrolled synthesis of the taxol C‐13 side chain: Methyl (2R,3S)‐3‐benzoylamino‐2‐hydroxy‐3‐phenylpropanoate

Addition of lithiated methoxyallene 5 to literature‐known amino aldehyde 3 followed by ozonolysis provided syn‐configurated α‐hydroxy‐β‐amino ester 6 in moderate overall yield and with an ee of 90%. The predominant formation of syn‐compounds may be due to a chelate controlled addition step.     

Synthesis and Highly Stereoselective Hydrogenation of the Statin Precursor Ethyl (5S)‐5,6‐Isopropylidenedioxy‐3‐oxohexanoate

A search for the large‐scale preparation of (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoates ( 2 ) – a key intermediate in the synthesis of pharmacologially important statins – starting from (S)‐malic acid is described. The synthesis of the required initial compound methyl (3S)‐3,4‐(isopropylidenedioxy)butanoate ( 1 ) by Moriwake’s reduction of dimethyl (S)‐malate ( 3 ) has been improved. Direct 2‐C chain elongation of ester 1 using the lithium enolate of tert‐butyl acetate has been shown to be successful at a 3‐ to 5‐fold excess of the enolate. Unfortunately, the product, tert‐butyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate ( 2a ) is unstable during distillation. Ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate ( 2b ) was prepared alternatively on a multigram scale from (3S)‐3,4‐(isopropylidenedioxy)butanoic acid ( 7 ) by activation with N,N′‐carbonyldiimidazole and subsequent reaction with Mg(OOCCH₂COOEt)₂. A convenient pathway for the in situ preparation of the latter is also described. Ethyl ester ( 2b ) can be advantageously purified by distillation. The stereochemistry of the catalytic hydrogenation of β‐keto ester ( 2b ) to ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐hydrohyhexanoate (syn‐ 6 and anti‐ 6 ) has been studied using a number of homogeneous achiral and chiral Rh(I) and Ru(II) complexes with phosphine ligands. A comparison of Rh(I) and Ru(II) catalysts with (S)‐ and (R)‐BINAP as chiral ligands revealed opposite activity in dependence on the polarity of the solvent. No influence of the chiral backbone of substrate 2b on the enantioselectivity was noted. A ratio of syn‐ 6 /anti‐ 6 =2.3 was observed with an achiral (Ph₃P)₃RuCl₂ catalyst. Ru[(R)‐Tol‐BINAP]Cl₂ neutralized with one equivalent of AcONa afforded the most efficient catalytic system for the production of optically pure syn‐(5S)‐5,6‐isopropylidenedioxy‐3‐hydroxyhexanoate (syn‐ 6 ) at a preparative substrate/catalyst ratio of 1000:1.