Synthesis of poly(β‐pinene)‐g‐polystyrene from allylic brominated poly(β‐pinene)

Poly(β‐pinene) was brominated by N‐bromosuccinimide on the allylic carbons. Then the brominated product was activated by AlEt₂Cl to initiate the polymerization of styrene to give a β‐pinene/styrene graft copolymer. AlEt₂Cl was selected because it alone could not initiate the polymerization of styrene. The obtained graft copolymer was characterized by GPC, ¹H‐NMR, and DSC measurements, respectively. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 599–603, 2000     

Cationic copolymers of α,β‐poly‐(N‐2‐hydroxyethyl)‐DL‐aspartamide (PHEA) and α,β‐polyasparthylhydrazide (PAHy): synthesis and characterization

In the present study the derivatization of two water‐soluble synthetic polymers, α,β‐poly(N‐2‐hydroxyethyl)‐DL ‐aspartamide (PHEA) and α,β‐polyasparthylhydrazide (PAHy), with glycidyltrimethylammonium chloride (GTA) is described. This reaction permits the introduction of positive charges in the macromolecular chains of PHEA and PAHy in order to make easier the electrostatic interaction with DNA. Different parameters affect the reaction of derivatization, such as GTA concentration and reaction time. PHEA reacts partially and slowly with GTA; on the contrary the reaction of PAHy with GTA is more rapid and extensive. The derivatization of PHEA and PAHy with GTA is a convenient method to introduce positive groups in their chains and it permits the preparation of interpolyelectrolyte complexes with DNA. © 2000 Society of Chemical Industry     

Sodium Iodide/tert‐Butyl(dimethyl)silyl Chloride‐Induced Isomerization of 2,3‐Allenols to 2(E)‐Enals

Through an unexpected CC bond migration, 2(E)‐enals were efficiently prepared highly stereoselectively in moderate to good yields via the sodium iodide/tert‐butyl(dimethyl)silyl chloride (NaI/TBSCl)‐mediated reaction of the easily available 2,3‐allenols. Based on a careful mechanistic study, including control experiments and deuterium‐labeling experiments, an electron‐withdrawing substituent group in the 4 position has been proven to be crucial and a possible mechanism has been proposed.

     

Palladium(II)‐Catalyzed Aerobic Intermolecular Cyclization of Acrylic Acid with Alkenes to α‐Methylene‐γ‐butyrolactones

The methodology in this article is a palladium(II)/copper(II)‐ or palladium(II)‐catalyzed intermolecular cyclization of acrylic acid with alkenes to produce α‐methylene‐γ‐butyrolactone derivatives using molecular oxygen as an environmentally benign oxidant. In this system, the carboxylato, especially trifluoroacetato, or trimethylacetato ligand, plays a quite important role to afford a high catalytic activity by suppressing the deposition of palladium(0) black.     

Ionic Liquid, 1‐n‐Butyl‐3‐methylimidazolium Bis(trifluoromethanesulfonyl)imide,Resulted in the First Catalyst‐Free Aminohalogenation of Electron‐Deficient Alkenes

The 2‐Ns‐based aminohalogenation of α,β‐unsaturated ketones has been achieved in an ionic liquid, 1‐n‐butyl‐3‐methylimidazolium bis(trifluoromethanesulfonyl)imide {[bmim][N(SO₂CF₃)₂]}. [Bmim][N(SO₂CF₃)₂] was found to be superior not only to classical organic solvents but also to its counterpart, [bmim][BF₄], which was proven to be successful in the TsNCl₂‐based aminohalogenation but failed to give any product for this reaction. The present process takes the advantage of 2‐NsNCl₂ as the stable nitrogen/halogen source in a one‐pot operation without the use of any metal catalysts, it is convenient to perform without special protection of inert gases. Eight examples were examined with good to excellent stereoselectivity (1:5 to one isomer) and modest to good chemical yields (53–72 %).     

Ruthenium(II)‐Catalyzed Protocol for Preparation of Diverse α,β‐ and β,β‐Dihaloenones from Diazodicarbonyls

Efficient one‐step syntheses of α,β‐ and β,β‐dihaloenones were achieved by ruthenium(II)‐catalyzed reactions between cyclic or acyclic diazodicarbonyl compounds and oxalyl chloride or oxalyl bromide in moderate to good yields. This methodology offers several significant advantages, which include ease of handling, mild reaction conditions, one‐step reaction, and the use of an effective and non‐toxic catalyst. The synthesized compounds were further transformed into highly functionalized novel molecules bearing aromatic rings on the enone moiety using the Suzuki reaction.

     

Highly Enantioselective Phase‐Transfer Catalytic α‐Alkylation of α‐tert‐Butoxycarbonyllactams: Construction of β‐Quaternary Chiral Pyrrolidine and Piperidine Systems

A new enantioselective α‐alkylation of α‐tert‐butoxycarbonyllactams for the construction of β‐quaternary chiral pyrrolidine and piperidine core systems is reported. α‐Alkylations of N‐methyl‐α‐tert‐butoxycarbonylbutyrolactam and N‐diphenylmethyl‐α‐tert‐butoxycarbonylvalerolactam under phase‐transfer catalytic conditions (solid potassium hydroxide, toluene, −40 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐3,3′,5,5′‐tetrahydro‐2,6‐bis(3,4,5‐trifluorophenyl)‐4,4′‐spirobi[4H‐dinaphth[2,1‐c:1′,2′‐e]azepinium] bromide [(S,S)‐NAS Br] (5 mol%) afforded the corresponding α‐alkyl‐α‐tert‐butoxycarbonyllactams in very high chemical (up to 99%) and optical yields (up to 98% ee). Our new catalytic systems provide attractive synthetic methods for pyrrolidine‐ and piperidine‐based alkaloids and chiral intermediates with β‐quaternary carbon centers.     

Multi‐Enzymatic Synthesis of Optically Pure β‐Hydroxy α‐Amino Acids

A novel enzymatic production system of optically pure β‐hydroxy α‐amino acids was developed. Two enzymes were used for the system: an N‐succinyl L ‐amino acid β‐hydroxylase (SadA) belonging to the iron(II)/α‐ketoglutarate‐dependent dioxygenase superfamily and an N‐succinyl L ‐amino acid desuccinylase (LasA). The genes encoding the two enzymes are part of a gene set responsible for the biosynthesis of peptidyl compounds found in the Burkholderia ambifaria AMMD genome. SadA stereoselectively hydroxylated several N‐succinyl aliphatic L ‐amino acids and produced N‐succinyl β‐hydroxy L ‐amino acids, such as N‐succinyl‐L ‐β‐hydroxyvaline, N‐succinyl‐L ‐threonine, (2S,3R)‐N‐succinyl‐L ‐β‐hydroxyisoleucine, and N‐succinyl‐L ‐threo‐β‐hydroxyleucine. LasA catalyzed the desuccinylation of various N‐succinyl‐L ‐amino acids. Surprisingly, LasA is the first amide bond‐forming enzyme belonging to the amidohydrolase superfamily, and has succinylation activity towards the amino group of L ‐leucine. By combining SadA and LasA in a preparative scale production using N‐succinyl‐L ‐leucine as substrate, 2.3 mmol of L ‐threo‐β‐hydroxyleucine were successfully produced with 93% conversion and over 99% of diastereomeric excess. Consequently, the new production system described in this study has advantages in optical purity and reaction efficiency for application in the mass production of several β‐hydroxy α‐amino acids.

     

Chemical Synthesis of the Epimeric (23R)‐ and (23S)‐Fluoro Derivatives of Bile Acids via Horner–Wadsworth–Emmons Reaction

A method for the synthesis of two (23R)‐ and (23S)‐epimeric pairs of 23‐fluoro‐3α,7α,12α‐trihydroxy‐5β‐cholan‐24‐oic acid and 23‐fluoro‐3α,7α‐dihydroxy‐5β‐cholan‐24‐oic acid is described. The key intermediates, 23,24‐dinor‐22‐aldehyde peracetates were prepared from cholic and chenodeoxycholic acids via the 24‐nor‐22‐ene, 24‐nor‐22ξ,23‐epoxy, and 23,24‐dinor‐22‐aldehyde derivatives. The Horner–Wadsworth–Emmons reaction of the 23,24‐dinor‐22‐aldehydes using triethyl 2‐fluoro‐2‐phosphonoacetate in the presence of LiCl and 1,8‐diazabicyclo[5,4,0]undec‐7‐ene (DBU), and subsequent hydrogenation of the resulting 23ξ‐fluoro‐22‐ene ethyl esters, followed by hydrolysis, gave a mixture of the epimeric (23R)‐ and (23S)‐fluorinated bile acids which were resolved efficiently by preparative RP‐HPLC. The stereochemical configuration of the fluorine atom at C‐23 in the newly synthesized compounds was confirmed directly by the X‐ray crystallographic data. The ¹H and ¹³C NMR spectral differences between the (23R)‐ and (23S)‐epimers were also discussed.     

Direct Decarboxylative Alkynylation of α,α‐Difluoroarylacetic Acids under Transition Metal‐Free Conditions

An efficient and generally applicable protocol for decarboxylative coupling of α,α‐difluoroarylacetic acids with ethynylbenziodoxolone (EBX) reagents has been developed, affording α,α‐difluoromethylated alkynes bearing various functional groups in moderate to excellent yields. Remarkably, this potassium persulfate (K₂S₂O₈)‐promoted reaction employs water as solvent under transition metal‐free conditions, thus providing a green synthetic approach to α,α‐difluoromethylated alkynes.

     

Bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol: an Improved Organocatalyst for the Asymmetric Epoxidation of α,β‐Enones

The asymmetric epoxidation of α,β‐enones by the readily available bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol and tert‐butyl hydroperoxide (TBHP) is described. Stereoelectronic substitution on the aryl moiety of diaryl‐2‐pyrrolidinemethanols was found to significantly affect the efficiency with respect to the previously reported (S)‐diphenyl‐2‐pyrrolidinemethanol. Improved reactivity and enantioselectivity were achieved with bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol at reduced catalyst loading (20 mol %) with ees up to 94% for chalcone epoxides under mild reaction conditions, whereas (S)‐diphenyl‐2‐pyrrolidinemethanol afforded a maximum ee of 80%. Interestingly, the methodology is applicable to the epoxidation of more challenging aliphatic or enolizable enones with good control of the asymmetric induction (up to 87% ee).     

Access to Both Enantiomers of α‐Chloro‐β‐keto Esters with a Single Chiral Ligand: Highly Efficient Enantioselective Chlorination of Cyclic β‐Keto Esters Catalyzed by Chiral Copper(II) and Zinc(II) Complexes of a Spiro‐2,2′‐bischroman‐Based Bisoxazoline Ligand

The spiro‐2,2′‐bichroman‐based chiral bisoxazoline ligands (SPANbox) were found to be highly efficient in copper(II)‐ and zinc(II)‐catalyzed asymmetric chlorinations of cyclic β‐keto esters with N‐chlorosuccinimide (NCS) as the chlorination reagent, to give the corresponding α‐chloro‐β‐keto esters in excellent yields in 5–30 min with ee values up to 97%. The copper(II) triflate and zinc(II) triflate complexes of a single SPANbox ligand demonstrated complementary results to each other with respect to the enantioselection, affording both antipodes of the chlorinated product enantiomers with good to excellent optical purities.     

Synthesis and characterization of polyrotaxanes comprising α‐cyclodextrins and poly(ε‐caprolactone) end‐capped with poly(butyl methacrylate)s

Biodegradable polyrotaxane‐based triblock copolymers were synthesized via the bulk atom transfer radical polymerization (ATRP) of n‐butyl methacrylate (BMA) initiated with polypseudo‐rotaxanes (PPRs) built from a distal 2‐bromoisobutyryl end‐capped poly(ε‐caprolactone) (Br‐PCL‐Br) with α‐cyclodextrins (α‐CDs) in the presence of Cu(I)Br/N,N,N′,N″,N″‐pentamethyldiethylenetriamine at 45 ºC. The structure was characterized in detail by means of ¹H NMR, gel permeation chromatography, wide‐angle X‐ray diffraction, DSC and TGA. When the feed molar ratio of BMA to Br‐PCL‐Br was changed from 128 to 300, the degree of polymerization of PBMA blocks attached to two ends of the PPRs was in the range 382 ? 803. Although about a tenth of the added α‐CDs were still threaded onto the PCL chain after the ATRP process, the movable α‐CDs made a marked contribution to the mechanical strength enhancement, blood anticoagulation activity and protein adsorption repellency of the resulting copolymers. Meanwhile, they could also protect the copolymers from the attack of H₂O and Lipase AK Amano molecules, exhibiting a lower mass loss as evidenced in hydrolytic and enzymatic degradation experiments. © 2013 Society of Chemical Industry     

Poly‐α,β‐(3‐hydroxypropyl)‐DL‐aspartamide: A new drug carrier

Poly‐α,β‐(3‐hydroxypropyl)‐DL ‐aspartamide (PHPA) was synthesized by the ring‐open reaction of polysuccinimide (PSI) and 3‐hydroxypropylamine. The polymer was characterized by ¹H‐NMR, ¹³C‐NMR, FTIR, and GPC. Mark–Houwink coefficients were obtained from viscometry and GPC measurements, K = 5.53 × 10⁻³ and α = 0.78 in water. The acute toxicity of PHPA was examined and it revealed no death in ICR mice up to the dose treated of 15.3 kg/kg, and hematological parameters showed no significant difference between treated and control animals. The potential use of PHPA as a drug carrier was also investigated. In a typical case, a contraceptive drug, norethindrone (NET), was bonded to PHPA, and the drug sustained released as long as 120 days an in vitro test. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 2411–2417, 2000     

Utilizing ultraviolet photooxidation as a pre‐treatment of volatile organic compounds upstream of a biological gas cleaning operation

Laboratory experiments were conducted to evaluate the potential to utilize ultraviolet (UV) photooxidation as a pre‐treatment to render recalcitrant volatile organic compounds into more biodegradable compounds. α‐Pinene was selected due to its low water solubility and low biodegradability. α‐Pinene‐contaminated gaseous streams with inlet loadings between 250 and 2500 g m^?3 h^?1 were passed through an annular reactor equipped with a UV lamp that emitted light at 254 nm and 185 nm wavelengths. The outlet stream containing UV photooxidation intermediates was then sparged through nanopure water that was then analyzed for its total organic carbon (TOC) content and subjected to batch biodegradability tests. UV photooxidation effectively degraded α‐pinene with a maximum removal rate of about 700 g m^?3 h^?1. The removal rate followed first order kinetics at low inlet loadings (less than 1200 g m^?3 h^?1) and approached zero order behavior at higher inlet loadings. The principal oxidizing species in the reactor was ozone. Of the total α‐pinene removed, measured as TOC, 50% was converted to water‐soluble and more biodegradable intermediates. The biodegradability of the resultant intermediates was similar to that of methyl ethyl ketone (MEK), which is 3–30 times more biodegradable than α‐pinene. These results show that the use of UV photooxidation is a promising and effective pre‐treatment technique for enhancing the biodegradability of hydrophobic and recalcitrant organic compounds such as α‐pinene. Copyright © 2004 Society of Chemical Industry     

N‐Heterocyclic Carbene‐Mediated Organocatalytic Transfer of Tin onto Aldehydes: New Access to α‐Silyloxyalkylstannanes and γ‐Silyloxyallylstannanes

A new, highly efficient and mild N‐heterocyclic carbene (NHC)‐mediated organocatalytic procedure for the transfer of tin from tributyl(trimethylsilyl)stannane (Bu₃SnSiMe₃) onto aldehydes for the preparation of α‐silyloxyalkylstannanes and γ‐silyloxyallylstannanes has been developed.     

An Efficient Cobalt(I)‐Catalysed Reformatsky Reaction using α‐Chloro Esters

An efficient cobalt(I )‐catalysed Reformatsky reaction using α‐chloro esters has been developed. The catalyst is prepared by reducing the cobalt(II ) chloride (5 %)/1,2‐bis(diphenylphosphino)ethane (dppe)(5 %)/zinc iodide (10 %) system with zinc metal in acetonitrile in the presence of both the α‐chloro ester and the carbonyl compound; good to excellent conversions to β‐hydroxy esters are obtained at room temperature in 2.5 h.     

The One‐Pot Wittig Reaction: A Facile Synthesis of α,β‐Unsaturated Esters and Nitriles by Using Nanocrystalline Magnesium Oxide

Nanocrystalline magnesium oxide was found to be an effective heterogeneous, solid base catalyst for the one‐pot Wittig reaction to afford α,β‐unsaturated esters and nitriles in excellent yields with high E‐stereoselectivity in the presence of triphenylphosphine under mild conditions.     

Chemical Synthesis of Rare Natural Bile Acids: 11α‐Hydroxy Derivatives of Lithocholic and Chenodeoxycholic Acids

A method for the preparation of 11α‐hydroxy derivatives of lithocholic and chenodeoxycholic acids, recently discovered to be natural bile acids, is described. The principal reactions involved were (1) elimination of the 12α‐mesyloxy group of the methyl esters of 3α‐acetate‐12α‐mesylate and 3α,7α‐diacetate‐12α‐mesylate derivatives of deoxycholic acid and cholic acid with potassium acetate/hexamethylphosphoramide; (2) simultaneous reduction/hydrolysis of the resulting △¹¹‐3α‐acetoxy and △¹¹‐3α,7α‐diacetoxy methyl esters with lithium aluminum hydride; (3) stereoselective 11α‐hydroxylation of the △¹¹‐3α,24‐diol and △¹¹‐3α,7α,24‐triol intermediates with B₂H₆/tetrahydrofuran (THF); and (4) selective oxidation at C‐24 of the resulting 3α,11α,24‐triol and 3α,7α,11α,24‐tetrol to the corresponding C‐24 carboxylic acids with NaClO₂ catalyzed by 2,2,6,6‐tetramethylpiperidine 1‐oxyl free radical (TEMPO) and NaClO. In summary, 3α,11α‐dihydroxy‐5β‐cholan‐24‐oic acid and 3α,7α,11α‐trihydroxy‐5β‐cholan‐24‐oic acid have been synthesized and their nuclear magnetic resonance (NMR) spectra characterized. These compounds are now available as reference standards to be used in biliary bile acid analysis.     

Titanium‐Mediated Direct Carbon‐Carbon Double Bond Formation to α‐Trifluoromethyl Acids: A New Contribution to the Knoevenagel Reaction and a High‐Yielding and Stereoselective Synthesis of α‐Trifluoromethylacrylic Acids

An efficient strategy for a high‐yielding and stereoselective synthesis of α‐trifluoromethyl unsaturated carboxylic acids directly from the reactions of 3,3,3‐trifluoropropanoic acid (CF₃CH₂COOH) with various aryl aldehydes in the presence of titanium tetrachloride (TiCl₄) is reported here for the first time, which is a valuable expansion for the classical Knoevenagel reaction. Because these compounds may have potential applications in organic electronics and can be easily converted to the corresponding fluorinated alcohols and amino acids with excellent bioactivity, this route should be a good choice for the preparation of α‐trifluoromethyl‐containing derivatives.