Alcohol-assisted phosphine catalysis: one-step syntheses of dihydropyrones from aldehydes and allenoates

This paper describes the phosphine-catalyzed annulation of methyl allenoate with various aromatic aldehydes to form 6-aryl-4-methoxy-5,6-dihydro-2-pyrones. In this reaction, the addition of an alcohol was necessary to induce dihydropyrone formation, with the optimal agent being methanol. Moreover, the addition of n-butyllithium suppressed the formation of the noncyclized product, leading to the exclusive isolation of the dihydropyrone. This method provides an efficient, one-step route toward disubstituted dihydropyrones from simple, stable starting materials.     

Enantioselective total syntheses of (-)-clasto-lactacystin beta-lactone and 7-epi-(-)-clasto-lactacystin beta-lactone

An alkylidene carbene 1,5-CH insertion has been used as a key step in an efficient enantioselective total synthesis of (-)-clasto-lactacystin beta-lactone, and its C7-epimer. An additional noteworthy feature of the synthesis is the use of a novel oxidative deprotection procedure, utilizing DMDO, for the conversion of a late-stage benzylidene acetal into a primary alcohol and a secondary benzoate ester.     

Structural analysis of spiro beta-lactone proteasome inhibitors

Spiro beta-lactone-based proteasome inhibitors were discovered in the context of an asymmetric catalytic total synthesis of the natural product (+)-lactacystin (1). Lactone 4 was found to be a potent inhibitor of the 26S proteasome, while its C-6 epimer (5) displayed weak activity. Crystallographic studies of the two analogues covalently bound to the 20S proteasome permitted characterization of the important stabilizing interactions between each inhibitor and the proteasome's key catalytic N-terminal threonine residue. This structural data support the hypothesis that the discrepancy in potency between 4 and 5 may be due to differences in the hydrolytic stabilities of the resulting acyl enzyme complexes.     

Capsules from Pickering emulsion templates

Following the resurgence of interest in particle-stabilised or Pickering emulsions recently, the preparation of capsules from such templates has become feasible. We review some of the recent activity in this area and focus on both the methods used to reinforce the particle shell and the applications of these novel capsules, which may be empty or liquid-filled. The methods reported include interfacial polymerisation or crystallisation, interfacial cross-linking, the use of a sacrificial template, formation of polymer layers, gelation and evaporation from multiple emulsions. Potential applications are in the areas of wastewater treatment, perfume encapsulation, drug/dye release and as self-healing coatings.     

Enantioselective beta-lactone formation from ketene and aldehydes catalyzed by a chiral oxazaborolidine

[reaction: see text] A novel catalytic system has been developed for the enantioselective synthesis of beta-lactones from ketene and aldehydes.     

Enantioenriched synthesis of Escitalopram using lithiation-borylation methodology

The asymmetric synthesis of Escitalopram has been completed using a lithiation-borylation reaction as the key step. Suitably functionalized enantioenriched carbamate (er 98:2) and boronic ester coupling partners were prepared and following deprotonation with s-BuLi and borylation, the tertiary alcohol was obtained in 42% yield and 93:7 er. The lithiation-borylation reaction was found to tolerate nitrile, benzylic alcohol and N-Boc functionalities. The tertiary alcohol was converted to Escitalopram in three further steps.     

Novel bicyclization reaction leading to a fused beta-lactone

[reaction: see text] The reaction of acrylyl chloride with the above amino ketone in the presence of pyridine produces bicyclic beta-lactones rather than the corresponding acrylamide, which can be the major product under other conditions.     

Hybrid protein-lipid patterns from aluminum templates

An aqueous aluminum liftoff process suitable for fabrication of hybrid patterns of protein and supported lipid membrane on silica surfaces is described. Patterned aluminum thin films, which can be produced by conventional optical or electron beam lithography, are employed as sacrificial protecting layers to define the geometry of the protein-lipid patterns. The aluminum is lifted off in a mildly basic aqueous solution, which preserves the integrity of bound protein layers. The newly exposed substrate can then be filled with supported membrane by exposure to an aqueous vesicle suspension. The final substrate consists of patterned protein and lipid membranes with spatial resolution determined by aluminum patterns, down to 200 nm line widths in this case. Inorganic surfaces were characterized by atomic force microscopy and X-ray photoelectron spectroscopy while supported bilayers and protein patterns were characterized by epifluorescence microscopy.     

Stereodivergent Olefination of Enantioenriched Boronic Esters

A stereodivergent coupling reaction between vinyl halides and boronic esters is described. This coupling process proceeds without a transition‐metal catalyst, instead proceeding by electrophilic selenation or iodination of a vinyl boronate complex followed by stereospecific syn or anti elimination. Chiral, nonracemic boronic esters could be coupled with complete enantiospecificity. The process enables the highly stereoselective synthesis of either the E or Z alkene from a single isomer of a vinyl coupling partner.     

Enantioselective assembly of substituted dihydropyrones via organocatalytic reaction in water media

The diarylprolinol ether/HOAc-catalyzed cascade Michael addition and cyclization of aldehydes and alpha-keto-alpha,beta-unsaturated esters proceeds smoothly in water to afford cyclic hemiacetals, which are oxidized to furnish highly functionalized 3,4,5,6-tetrasubstituted dihydropyrones with excellent enantioselectivities.     

Ring opening/fragmentation of dihydropyrones for the synthesis of homopropargyl alcohols

Ring-opening/C-C bond cleavage reactions induced by nucleophilic addition of methyl Grignard to 5,6-dihydro-2-pyrone (DHP) triflates 1 furnish homopropargyl alcohols (1 --> 2) stereospecifically with respect to the stereochemistry of 1. Carbonyl extrusion from DHP triflates provides a unified and operationally simple strategy for preparing chiral homopropargyl alcohols.     

Organocatalytic synthesis of beta-alkylaspartates via beta-lactone ring opening

Cinchona alkaloid-catalyzed reaction of ethyl glyoxylate with substituted ketenes, formed in situ, gives disubstituted beta-lactones in moderate yield and high enantiomeric excess. Subsequent azide ring opening, reduction, and ester hydrolysis allows access to chiral beta-alkyl aspartates.     

Patterned metal nanowire arrays from photolithographically-modified templates

An effective procedure for the fabrication of patterned nanowire arrays with micron-sized features is presented. Photolithographic methods are utilized to form set patterns onto porous anodic alumina membranes (AAM), and these modified membranes can then be used in the electrochemical growth of nanowire arrays. This approach readily allows the formation of a variety of nanowire array patterns with line widths down to several microns.     

Sub-micrometer-sized metal tubes from electrospun fiber templates

Metallic tubes have been synthesized by a polymer-based template approach using electroless deposition. Gold, copper, and nickel were deposited as thin films on sub-micrometer polymer fibers which ranged in diameter from approximately 160 to 400 nm. After thermal degradation of the template fibers at 300 and 650 degrees C, tubes between 450 and 730 nm were obtained with wall thicknesses of 50-150 nm. Characterization by scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and powder X-ray diffraction indicate that the tubes have a face-centered cubic structure with [111] preferred orientation for all of the metals investigated and that the tube walls are polycrystalline, composed of nanoparticles, ranging in size from 5.0 to 25.0 nm.     

Anisotropic cellular structures from semi-crystalline polymer templates

We report an investigation to determine the effect of an anisotropic semi-crystalline template on the resulting cell morphology of microcellular polymeric foams generated in these materials. Poly(ethylene terephthalate) (PET)-polystyrene (PS) composite foams are prepared by using supercritical carbon dioxide (scCO₂) not only as a foaming agent but also as a transport medium of styrene and initiator into a biaxially-oriented PET templating film. The composite foam so obtained demonstrates a highly interpenetrating network verified by a single Tg of 98°C. Substrate orientation is observed not to dictate the cell formation; however highly anisotropic swelling and a shape-templating phenomenon is observed, with the most significant dimension change in the thickness of the film. Introducing confinement in the direction of maximum dimension change is found to introduce a highly anisotropic lamellar cell architecture.     

Practical beta-lactone synthesis: epoxide carbonylation at 1 atm

[reaction: see text] A readily prepared bimetallic catalyst is capable of effecting epoxide carbonylation to produce beta-lactones at substantially lower CO pressures than previously reported catalyst systems. A functionally diverse array of beta-lactones is produced in excellent yields at CO pressures as low as 1 atm. This procedure allows for epoxide carbonylation on a multigram scale without the requirement of specialized, high-pressure equipment.     

Theory-guided design of Brønsted acid-assisted phosphine catalysis: synthesis of dihydropyrones from aldehydes and allenoates

The phosphine-catalyzed addition of 2,3-butadienoates to aldehydes has been extended to the formation of disubstituted dihydro-2-pyrones. The requisite shift in equilibrium of the intermediate zwitterionic β-phosphonium dienolates toward the s-cis intermediate was accomplished through the use of a Brønsted acid additive, which disrupts the favorable Coulombic interaction present in the s-trans intermediate. The detailed nature of the synergistic interactions involving the Brønsted acid additives and phosphine involved in the formation of s-cis β-phosphonium dienolates was analyzed through a series of DFT calculations. Unlike previously reported annulations of aldehydes with allenoates, where trialkylphosphines are optimal catalysts, in this study triphenylphosphine was also found for the first time to be a suitable catalyst for the synthesis of dihydropyrones. This method provides a one-step route toward functionalized dihydropyrones from simple, stable starting materials. In addition, new reaction pathways of phosphine-catalyzed allene annulations are unveiled, with the formation of dihydropyrones being the first example of dual activation in this sphere.