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.

     

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     

Michael Reaction of Nitroalkanes with β‐Nitroacrylates under a Solid Promoter: Advanced Regio‐ and Diastereoselective Synthesis of Nitro‐Functionalized α,β‐Unsaturated Esters and 1,3‐Butadiene‐2‐carboxylates

A new class of nitro‐functionalized α,β‐unsaturated esters has been prepared by a regio‐ and diastereoselective Michael addition of nitroalkanes to β‐nitroacrylates, performed at room temperature, under carbonate on polymer as promoter, and in the presence of ethyl acetate as eco‐friendly solvent. Moreover, by the modular choice of the reaction conditions the method allows the synthesis of 1,3‐butadiene‐2‐carboxylates.     

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.     

Negative effect of stretching on the development of β‐phase in β‐nucleated isotactic polypropylene

On the premise that shear in the slit die of an extruder was minimized as far as possible, β‐nucleated isotactic polypropylene (iPP) was extruded. Simultaneously, once the extrudate (in the melt state) left the die exit, it was stretched at various stretching rates (SRs). For iPP with a low content of β‐nucleating agent (β‐NA), the crystallinity of β‐phase (X_β) initially increases with increasing SR, and then decreases slightly with further increase in SR. However, for iPP containing a higher content of β‐NA, with increasing SR, X_β decreases monotonically, indicating a negative effect of SR on β‐phase formation. Small‐angle X‐ray scattering and polarized optical microscopy experiments reveal that, when SR is less than 30 cm min^?1, the increasing amount of row nuclei induced by increasing SR is mainly responsible for the increase of X_β. In contrast, when SR exceeds 30 cm min^?1, the overgrowth of shish structures unexpectedly restrains the development of β‐phase, and spatial confinement is considered as a better explanation for the suppression of β‐phase. Copyright © 2011 Society of Chemical Industry     

Structural elucidation and iron oxidation states in situ formed β‐Ca3(PO4)2/α‐Fe2O3 composites

A detailed structural analysis on the in situ synthesized β‐Ca₃(PO₄)₂/α‐Fe₂O₃ composites is demonstrated. Compositional ratios, the influence and occupancy of iron at the β‐Ca₃(PO₄)₂ lattice, oxidation state of iron in the composites are derived from analytical techniques involving XRD, FT‐IR, Raman, refinement of the powder X‐ray diffraction and X‐ray photoelectron spectroscopy. Iron exists in the Fe³⁺ state throughout the investigated systems and favors its occupancy at the Ca²⁺(5) site of β‐Ca₃(PO₄)₂ until critical limit, and thereafter crystallizes as α‐Fe₂O₃ at ambient conditions. Fe³⁺ occupancy at the β‐Ca₃(PO₄)₂ lattice yields a Ca₉Fe(PO₄)₇ structure that is isostructural with its counterpart. A strong rise in the soft ferromagnetic behavior of β‐Ca₃(PO₄)₂/α‐Fe₂O₃ composites is obvious that depends on the content of α‐Fe₂O₃ in the composites. Overall, the diverse level of iron inclusions at the calcium phosphate system with a Ca/P ratio of 1.5 yields a structurally stable β‐Ca₃(PO₄)₂/α‐Fe₂O₃ composites with assorted compositional ratios.     

Ruthenium‐Catalyzed Oxidation of the Porphyrin β,β′‐Pyrrolic Ring: A General and Efficient Approach to Porpholactones

We describe an efficient ruthenium‐catalyzed oxidation of the β,β′‐pyrrolic ring on the porphyrin periphery. Through the conversion of a β,β′‐double bond to a lactone moiety, the direct preparation of porpholactones from porphyrins is achieved, which previously suffered from needing toxic reagents, multiple synthetic steps and low yields. The generality of this method has been investigated with various porphyrins with different electronic and steric effects, even some metalloporphyrins, and so represents a general and efficient approach for the synthesis of the intriguing porpholactone derivatives.     

Effect of nucleating duality on the formation of γ‐phase in a β‐nucleated isotactic polypropylene copolymer

BACKGROUND: It is a challenge for polymer processing to promote the formation of γ‐phase under atmospheric conditions in isotactic polypropylene (iPP) copolymer containing chain errors. Incorporation of an α‐nucleator in iPP copolymer seems reasonable since it can enhance non‐isothermal crystallization. Up to now, however, the issue regarding a β‐nucleated iPP copolymer still remains unclear, which is the subject of this study. RESULTS: The results indicate that the γ‐phase indeed occurs in a β‐nucleated random iPP copolymer with ethylene co‐unit (PPR) sample and becomes predominant at slow cooling rates (e.g. 1 °C min^?1) where the formation of the β‐form is suppressed to a large extent. With detailed morphological observations the formation of γ‐phase in the β‐nucleated PPR sample at slow cooling rate is unambiguously attributed to the nucleating duality of the β‐nucleator towards α‐ and β‐polymorphs. The α‐crystals, induced by the β‐nucleator, serve as seeds for the predominant growth of the γ‐phase. Moreover, the presence of the β‐nucleator, acting as heterogeneous nuclei, promotes the formation of γ‐phase in the nucleated PPR sample, at least to some extent. CONCLUSION: The findings in this study extend our insights into the formation of γ‐phase in β‐nucleated iPP copolymer and, most importantly, provide an alternative route to obtain iPP rich in γ‐phase. Copyright © 2008 Society of Chemical Industry     

Highly Enantioselective Michael Addition of Cyclic 1,3‐Dicarbonyl Compounds to β,γ‐Unsaturated α‐Keto Esters

A highly enantioselective Michael addition of cyclic 1,3‐dicarbonyl compounds to β,γ‐unsaturated α‐keto esters catalyzed by amino acid‐derived thiourea‐tertiary‐amine catalysts is presented. Using 5 mol% of a novel tyrosine‐derived thiourea catalyst, a series of chiral coumarin derivatives were obtained in excellent yields (up to 99%) and with up to 96% ee under very mild conditions within a short reaction time.     

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     

Chemoenzymatic Preparation of Enantiopure Homoadamantyl β‐Amino Acid and β‐Lactam Derivatives

Racemic cis‐10‐azatetracyclo[7.2.0.1^2,6.1^4,8]tridecan‐11‐one was prepared from homoadamant‐4‐ene by chlorosulfonyl isocyanate addition. The transformation of the β‐lactam to the corresponding β‐amino ester followed by Candida antarctica lipase A‐catalyzed enantioselective (E>>200) N‐acylation with 2,2,2‐trifluoroethyl butanoate afforded methyl (1R,4R,5S,8S)‐5‐aminotricyclo[4.3.1.1^3,8]undecane‐4‐carboxylate and the (1S,4S,5R,8R)‐butanamide with>99% ee at 50% conversion. Alternatively, transformation of the β‐lactam to the corresponding N‐hydroxymethyl‐β‐lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) lipase‐catalyzed enantioseletive O‐acylation provided the (1S,4S,6R,9R)‐alcohol (ee=87%) and the corresponding (1R,4R,6S,9S)‐butanoate (ee>99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)‐butanoate, 2,2,2‐trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1S,4S,6R,9R)‐alcohol with time.     

Organocatalytic Enantioselective Aziridination of α‐Substituted α,β‐Unsaturated Aldehydes: Asymmetric Synthesis of Terminal Aziridines

The first example of a highly enantioselective organocatalytic aziridination of α‐substituted α,β‐unsaturated aldehydes is presented. The reaction is catalyzed by simple chiral amines and gives access to highly functional terminal azirdines containing an α‐tertiary amine stereocenter in high yields and enantiomeric ratios (95.5:4.5–98:2).     

A concise synthesis of single‐enantiomer β‐lactams and β‐amino acids using Rhodococcus globerulus

BACKGROUND: Pharmaceutical companies continue to evaluate β‐amino acids and β‐lactams in a range of drug candidates. The development of a highly efficient and selective bioresolution of cyclic β‐lactam substrates could yield enantiopure lactams and β‐amino acids with medicinal potential. The aim of this work was to discover and develop a biocatalyst capable of selectively hydrolysing β‐lactam substrates. RESULTS: Screening of our in‐house culture collection led to the discovery of a microorganism, Rhodococcus globerulus (NCIMB 41042) with β‐lactamase activity. Whole‐cell bioresolutions of the β‐lactams 1–4 were successfully carried out and in all cases enantiomeric excesses of the residual lactam and amino acid product were found to be greater than 98%. For one example, the bioresolution was optimised to operate at 60 g L^?1 substrate concentration with a 20% wt/wt cell paste loading. CONCLUSION: A microorganism, Rhodococcus globerulus (NCIMB 41042), capable of selectively hydrolysing a range of cyclic β‐lactams, has been discovered. A scalable whole‐cell bioresolution process has been developed, leading to the synthesis of multigram quantities of enantiomerically pure β‐lactams and β‐amino acids. Copyright © 2007 Society of Chemical Industry     

RuO4 staining and lamellar structure of α‐ and β‐PP

Monoclinic (α) and hexagonal (β) polypropylene (α‐ and β‐PP) were stained in the vapor of a ruthenium tetroxide solution prepared in situ. The effect of staining on the fusion behavior was investigated using a DSC. A staining duration between 10 and 24 h was found suitable for obtaining a good electron contrast between the crystalline and amorphous regions for TEM examination without causing severe damage to the crystals. The spherulites of the water‐quenched α‐PP were found to be composed of very fine cross‐hatched lamellae whose long period was about 10 nm. In comparison, the β‐PP spherulites crystallized isothermally at 130°C had a category 2 morphology and the lamellae have a long period of 20 nm. The morphology of the spherulite boundary varied depending on the contact angle between the lamellae of the neighboring spherulites. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1529–1538, 1999     

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.     

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.     

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.

     

The Synthesis of trans‐Perhydroindolic Acids and their Application in Asymmetric Domino Reactions of Aldehyde Esters with β,γ‐Unsaturated α‐Keto Esters

(2S,3aR,7aS)‐Perhydroindolic acid, the key intermediate in the synthesis of trandolapril, and its trans‐isomers, were readily prepared. These proline‐like molecules are unique in that they contain a rigid bicyclic structure, with two hydrogen atoms trans to each other at the bridgehead carbon atoms. These molecules were used successfully as chiral organocatalysts in asymmetric domino Michael addition/cyclization reactions of aldehyde esters with β,γ‐unsaturated α‐keto esters. They proved to have excellent catalytic behavior, allowing for the synthesis of multi‐substituted, enantiomerically enriched hemiacetal esters. Under optimal conditions (using 10 mol% catalyst loading), a series of β,γ‐unsaturated α‐keto esters was examined with up to 99% de, ee and yield, respectively. Additionally, the enantiomerically enriched hemiacetal esters could be readily transformed into their corresponding bioactive pyrano[2,3‐b]pyrans (possessing a multi‐substituted bicyclic backbone).     

Rhodium‐Catalyzed Asymmetric Hydroformylation of 1,1‐Disubstituted Allylphthalimides: A Catalytic Route to β3‐Amino Acids

The high enantioselective rhodium‐catalyzed hydroformylation of 1,1‐disubstituted allylphthalimides has been developed. By employing chiral ligand 1,2‐bis[(2S,5S)‐2,5‐diphenylphospholano]ethane [(S,S)‐Ph‐BPE], a series of β³‐aminoaldehydes can be prepared with up to 95% enantioselectivity. This asymmetric procedure provides an efficient alternative route to prepare chiral β³‐amino acids and alcohols.     

Organocatalytic Enantioselective Michael Reaction of Malononitrile with β,β‐Disubstituted Nitroalkenes

We have developed and optimized an enantioselective Michael reaction of malononitrile with β,β‐disubstituted nitroalkenes. This reaction was catalyzed by a cinchona alkaloid derived thiourea catalyst, producing products of high yields (up to 98 %) and stereoselectivities (up to 93 % ee). One of the adducts was used as an intermediate for the synthesis of dihydropyrrole derivative bearing a synthetically valuable quaternary chiral center.