Potassium Hydroxide‐Catalyzed Chemoselective Reduction of Cyclic Imides with Hydrosilanes: Synthesis of ω‐Hydroxylactams and Lactams

Potassium hydroxide‐catalyzed hydrosilylation exhibits excellent activity and chemoselectivity for the reduction of cyclic imides under mild reaction conditions. The chemoselectivity of the reduction system may be readily tuned by changing the identity and stoichiometry of the hydrosilanes: a polymethylhydrosiloxane (PMHS)/potassium hydroxide reduction system resulted in the reduction of various cyclic imides to the corresponding ω‐hydroxylactams in 70–94% yield, while the diphenylsilane (Ph₂SiH₂)/potassium hydroxide reduction system selectively afforded the aryl lactams in 33–95% yield. These catalytic protocols tolerate diverse functional groups and are easy to scale up.

     

Gold(I)‐Catalyzed Decarboxylation of Propargyl Carbonates: Reactivity Reversal of the Gold Catalyst from π‐Lewis Acidity to σ‐Lewis Acidity

A cationic gold(I)‐catalyzed decarboxylative etherification of propargyl carbonates to selectively produce propargyl ethers is reported. In the reaction the gold(I) catalyst shows a distinct σ‐Lewis acidity rather than the commonly observed π‐Lewis acidity, and thus catalyzes the decarboxylation of a variety of propargyl carbonates to give the corresponding propargyl ethers with high selectivity. This reaction represents a rare example of the tunable reactivity of cationic gold(I) complexes between σ‐Lewis acidity and π‐Lewis acidity.

     

Synthesis of ω‐amino‐α‐phenylcarbonate alkanes and their polymerization to [n]‐polyurethanes

Aliphatic [n]‐polyurethanes have recently been synthesized from ω‐isocyanato‐α‐alkanols or, more traditionally, by cationic ring‐opening polymerization of cyclourethanes or by the Bu₂Sn(OMe)₂‐promoted polycondensation of ω‐hydroxy‐α‐O‐phenylurethane alkanes. For the latter procedures, the conditions employed do not seem to be suitable for highly functionalized monomers. In contrast, the polymerization of ω‐amino‐α‐phenylcarbonate alkanes is expected to occur under milder conditions. ω‐Amino‐α‐phenylcarbonate alkanes have been synthesized from 6‐aminohexanol (1) and 3‐aminopropanol (6). The procedure involves the N‐Boc protection of the amino group, followed by activation of the alcohol. Removal of the N‐Boc affords the corresponding ω‐amino‐1‐O‐phenyloxycarbonyloxyalkane hydrochlorides. Other oligomeric comonomers between 1 and 6 have been prepared. The polymerization of these precursors takes place in the absence of metal catalysts to afford the corresponding linear and regioregular [n]‐polyurethanes. The procedure described is useful for the preparation of stable ω‐amino‐α‐phenylcarbonate alkane derivatives, which possess varied chain lengths between the terminal functions. These monomers yield [n]‐polyurethanes having various structures starting from just two aminoalkanols. The polyurethanes were obtained in high yields, with reasonable molecular weight and polydispersity values, and they were characterized spectroscopically and thermally. These studies reveal constitutionally uniform structures that are free of carbonate or urea linkages. Copyright © 2010 Society of Chemical Industry     

Zinc‐Catalyzed Enantioselective Hydrosilylation of Imines

The highly enantioselective reduction of imines is achieved by employing chiral Zn/diamine catalysts. This new catalytic protocol offers attractive features such as use of a non‐precious metal and an inexpensive silane, easy modification of chiral diamine ligands and provides ready access to chiral amines in good yields and with excellent enantioselectivities.     

Polyaniline doped with α, ω‐alkanedisulfonic acids: preparation and characterization

The use of α, ω‐alkanedisulfonic acid, HO₃S(CH₂)_nSO₃H (n = 1, 4, 6 and 12), as a dopant for polyaniline (PANi) was investigated. This series of disulfonic acids with varying chain lengths were synthesized and used in the doping of PANi. The doped polymers showed conductivity in the range 10^?2 to 10^?1 S cm^?1. Thermal studies showed that the doped polymers, depending on the chain length of α,ω‐alkanedisulfonic acid, were stable up to ca 300 °C and the thermal stability decreased with increasing dopant chain length. The thermal stability of α,ω‐alkanedisulfonic acid‐doped PANi was higher than that of alkanesulfonic acid‐doped PANi which typically degrades around 250 °C, suggesting a moderately broader processing window for α,ω‐alkanedisulfonic acid‐doped PANi for blending with other thermoplastics. Copyright © 2012 Society of Chemical Industry     

Synthesis and characterization of α‐butyl‐ω‐N,N‐dihydroxyethylaminopropylpolydimethylsiloxane

α‐Butyl‐ω‐N,N‐dihydroxyethylaminopropylpolydimethylsiloxane, a monotelechelic polydimethylsiloxane with a diol‐end group, which is used to prepare polyurethane–polysiloxane graft polymer, was successfully synthesized. The preparation included five steps, which are hydroxyl protection, alkylation, anionic ring‐opening polymerization, hydrosilylation, and deprotection. The products were characterized by FTIR, GC, LC‐MS, ¹H NMR, and elemental analysis. The results showed that each step was successfully carried out and the targeted products were synthesized in all cases. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Zinc‐Catalyzed Stereo‐ and Regioselective 1,4‐Hydrative Fluorination of 3‐En‐1‐ynamides with Selectfluor

Zinc‐catalyzed 1,4‐oxofluorinations of 3‐en‐1‐ynamides with Selectfluor in acetonitrile/water proceeded with high regio‐ and stereoselectivity, giving E‐configured γ‐fluoro‐α,β‐unsaturated amides efficiently. Our control experiments indicate that kinetically unstable C‐bound zinc dienolates are chemically reactive to undergo S_E2′‐electrophilic fluorinations whereas the detectable O‐bound dienolates preferably undergo protodemetalation reactions instead.

     

Chiral Lewis Base‐Catalyzed,Enantioselective Reduction of Unprotected β‐Enamino Esters with Trichlorosilane

Catalytic asymmetric reduction of N‐unsubstituted β‐enamino esters represents a major challenge for asymmetric catalysis. In this paper, the first organocatalytic system that could be used for the asymmetric hydrosilylation of N‐unsubstituted β‐enamino esters has been developed. Using N‐tert‐butylsulfinyl‐L ‐proline‐derived amides and L ‐pipecolinic acid‐derived formamides as catalyst, a broad range of β‐aryl‐ and β‐alkyl‐substituted free β‐amino esters could be prepared with high yields and enantioselectivities. The practicality was illustrated by the gram‐scale asymmetric synthesis of ethyl (R)‐3‐amino‐3‐phenylpropanoate and isopropyl (S)‐3‐amino‐4‐(2,3,5‐trifluorophenyl)butanoate. The resulting product can be smoothly transformed to the FDA approved medicines dapoxetine and sitagliptin in a short synthetic route.

     

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.     

Titanium‐Catalyzed Enantioselective Synthesis of α‐Ambrinol

We describe the first enantioselective synthesis of the odorant compound (−)‐α‐ambrinol (96% ee) from commercial geranylacetone. The key steps are a Jacobsen’s asymmetric epoxidation and a titanium‐catalyzed stereoselective cyclization initiated by radical epoxide opening. The oxirane ring opening proceeds with retention of configuration at the epoxide chiral center, giving a secondary alcohol which can be advantageously exploited to raise the ee provided by the synthetic sequence. We also synthesized (+)‐α‐ambrinol by a closely related procedure, showing the synthetic versatility of combining titanium‐catalyzed cyclization with Jacobsen’s epoxidation reactions.     

High activity of rare earth tetrahydroborates for ring‐opening polymerization of ω‐pentadecalactone

Ring‐opening polymerization of ω‐pentadecalactone (PDL) by tetrahydroborate complexes of rare earth metals, Ln(BH₄)₃(THF)₃ (Ln = La ( 1 ), Nd ( 2 ), Y ( 3 )), was studied. These complexes showed high activity for PDL polymerization in THF at 60°C. Among the complexes 1 – 3 , the neodymium complex 2 was most active. The obtained poly(PDL) was demonstrated to be hydroxy‐telechelic by ¹H‐NMR and MALDI‐TOF MS spectroscopy. Biodegradation of the poly(PDL) in compost at 60°C was investigated, where 18% weight loss of the samples was observed after 280 days. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Enhancing Thermostability and Organic Solvent Tolerance of ω‐Transaminase through Global Incorporation of Fluorotyrosine

Here, we have utilized the incorporation of non‐canonical amino acids as a tool kit to improve enzyme properties for organic synthesis applications. The global incorporation of 3‐fluorotyrosine (FY) into ω‐transaminase (ω‐TA) to give ω‐TA[FY] enhanced the thermostability and organic solvent tolerance without altering substrate specificity and enantioselectivity. Moreover, ω‐TA[FY] was able to completely convert 25 mM of acetophenone into (S)‐1‐phenylethylamine (ee>99%) in the presence of 20% DMSO (v/v) which is ∼2‐fold higher when compared to wild‐type ω‐TA.

     

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.     

Structural Determinants for the Non‐Canonical Substrate Specificity of the ω‐Transaminase from Paracoccus denitrificans

Substrate binding pockets of ω‐transaminase (ω‐TA) consist of a large (L) pocket capable of dual recognition of hydrophobic and carboxyl substituents, and a small (S) pocket displaying a strict steric constraint that permits entry of a substituent no larger than an ethyl group. Despite the unique catalytic utility of ω‐TA enabling asymmetric reductive amination of carbonyl compounds, the severe size exclusion occurring in the S pocket has limited synthetic applications of ω‐TA to access structurally diverse chiral amines and amino acids. Here we report the first example of an ω‐TA whose S pocket shows a non‐canonical steric constraint and readily accommodates up to an n‐butyl substituent. The relaxed substrate specificity of the (S)‐selective ω‐TA, cloned from Paracoccus denitrificans (PDTA), afforded efficient asymmetric syntheses of unnatural amino acids carrying long alkyl side chains such as L ‐norvaline and L ‐norleucine. Molecular modeling using the recently released X‐ray structure of PDTA could pinpoint an exact location of the S pocket which had remained dubious. Entry of a hydrophobic substituent in the L pocket was found to have the S pocket accept up to an ethyl substituent, reminiscent of the canonical steric constraint. In contrast, binding of a carboxyl group to the L pocket induced a slight movement of V153 away from the small‐pocket‐forming residues. The resulting structural change elicited excavation of the S pocket, leading to formation of a narrow tunnel‐like structure allowing accommodation of linear alkyl groups of carboxylate‐bearing substrates. To verify the active site model, we introduced site‐directed mutagenesis to six active site residues and examined whether the point mutations alleviated the steric constraint in the S pocket. Consistent with the molecular modeling results, the V153A variant assumed an elongated S pocket and accepted even an n‐hexyl substituent. Our findings provide precise structural information on substrate binding to the active site of ω‐TA, which is expected to benefit rational redesign of substrate specificity of ω‐TA.

     

Expanding Substrate Specificity of ω‐Transaminase by Rational Remodeling of a Large Substrate‐Binding Pocket

Production of structurally diverse chiral amines via biocatalytic transamination is challenged by severe steric interference in a small active site pocket of ω‐transaminase (ω‐TA). Herein, we demonstrated that structure‐guided remodeling of a large pocket by a single point mutation, instead of excavating the small pocket, afforded desirable alleviation of the steric constraint without deteriorating parental activities toward native substrates. Molecular modeling suggested that the L57 residue of the ω‐TA from Ochrobactrum anthropi acted as a latch that forced bulky substrates to undergo steric interference with the small pocket. Removal of the latch by a L57A substitution allowed relocation of the small pocket and dramatically improved activities toward various arylalkylamines and alkylamines (e.g., 1100‐fold increase in k_cat/K_M for α‐propylbenzylamine). This approach may provide a facile strategy to broaden the substrate specificity of ω‐TAs.

     

Diastereoselective Synthesis of Six‐Membered Carbocyclic Spirooxindoles via 6π‐Electrocyclization of 3‐Dienylidene‐2‐ oxindoles

The Wittig reaction of isatin derivatives with Morita–Baylis–Hillman bromides of cinnamaldehydes afforded 3‐dienylidene‐2‐oxindoles. These trienes were converted into the corresponding spirooxindoles in a stereoselective manner in refluxing toluene in good yields. The diastereomeric spirooxindoles could be obtained stereoselectively by adding a catalytic amount of palladium(II) acetate via the palladium‐catalyzed isomerization of EEE‐trienes to ZEE‐trienes followed by a more facile 6π‐electrocyclization process. The obtained spirooxindoles could be further functionalized by palladium‐catalyzed oxidative arylation, thionation with Lawesson’s reagent, catalytic hydrogenation and Friedel–Crafts‐type reaction.

     

Enantioselective Hydrogenation of β‐Acylamino Acrylates Catalyzed by Rhodium(I)‐Monophosphite Complexes

Chiral rhodium(I) complexes bearing monophosphite ligands, prepared from chiral Binol and (L )‐menthol, were found to be efficient catalysts for the asymmetric hydrogenation of β‐acylamino acrylates with ee values up to 94%.     

Emulsion copolymerization of tetrafluoroethylene with ω‐chlorotetrafluoroethyltrifluorovinyl ether and the synthesized copolymer properties

Emulsion copolymerization of ω‐chlorotetrafluoroethyltrifluorovinyl ether (Cl(CF₂)₂OCF = CF₂ (FVE)) with tetrafluoroethylene (CF₂ = CF₂ (TFE)) was investigated at various monomer ratios. The copolymerization rate is below the rate of TFE homopolymerization and the copolymerization kinetics depends on the FVE content in the reaction medium. The copolymer composition is very similar if the FVE content in monomer mixture is ≤2.5 mol %. However, the percent amount of FVE in the copolymer, the copolymerization rate, and molecular mass of synthesized copolymers decrease noticeably with increase in the FVE content in the monomer mixture. The constants of copolymerization are r₁= 2.8 (TFE) and r₂ = 0.03 (FVE). The copolymer is a statistical polymer consisting of TFE blocks and individual FVE molecules between the blocks. The average molecular mass of copolymers is significantly less than that of the TFE homopolymer (PTFE) synthesized at the same conditions. The morphologies of PTFE and copolymer powders were investigated by thermomechanical analysis and are not similar. The copolymer has a completely amorphous diblock morphology depending on the FVE content. The introduction of FVE molecules into the copolymer macromolecules is accompanied by reduction of the crystalline portion of copolymer. If the FVE content in copolymer is ≥3.5 mol %, the copolymer macromolecules completely lose the ability to form crystalline portions as a result of their amorphicity. The introduction of up to 2.4 mol % FVE into the copolymer macromolecules yields a highly thermostable and meltable copolymer which can be processed by using the industrial processes used widely for thermoplastics. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and characterization of poly{[α‐maleic anhydride‐ω‐methoxy‐poly(ethylene glycol)]‐co‐(ethyl cyanoacrylate)} copolymer nanoparticles

Poly{[α‐maleic anhydride‐ω‐methoxy‐poly(ethylene glycol)]‐co‐(ethyl cyanoacrylate)} (PEGECA) copolymers were prepared by radical polymerization of macromolecular poly(ethylene glycol) monomers (PEGylated) and ethyl 2‐cyanoacrylate in solvent. The structures of the copolymer were characterized by Fourier‐transform infrared (FTIR) and proton nuclear magnetic resonance (¹H‐NMR). The morphology and size of the PEGECA nanoparticles prepared by nanoprecipitation techniques were investigated by transmission electron microscopy (TEM) and photon correlation spectroscopy (PCS) methods. The results show that the PEGECA can self‐assemble into highly stable nanoparticles in aqueous media, and inner core and outer shell morphology. The size of the nanoparticles was strongly influenced by the solvent character and the copolymer concentration in the organic solvents. A hydrophobic drug, ibuprofen, was effectively incorporated into the nanoparticles, which provides a delivery system for ibuprofen and other hydrophobic compounds. Copyright © 2005 Society of Chemical Industry