Single bead and hard tag decoding using accurate isotopic difference target analysis-encoded combinatorial libraries

A single fully automated generic microbore liquid chromatography electrospray time-of-flight protocol has been developed for the analysis of single beads, single beads with analytical constructs, and isotopically labelled dialkylamine hard tags. The protocol relies upon the incorporation of an isotopic signature into the linker and/or derivatising molecule to give a specific isotopic ratio together with an accurate isotopic difference. These properties facilitate highly specific and sensitive analysis of beads and hard tags using accurate isotopic difference analysis (AIDA) without prior knowledge of the molecular weight. Three open access methods with automated processing have been developed around a core generic approach.     

Double elimination protocol for access to unsymmetrically substituted aromatic polyynes starting from sulfones and aldehydes

A double elimination protocol has been established for access to unsymmetrically substituted aromatic polyynes by use of dialdehyde and substituted benzylic or propargylic sulfones as starting compounds. For this protocol, various substituted sulfones and phthalaldehydes were usable giving rise to the formation of the desired substituted aromatic polyynes.     

Novel synthesis of oxa[9]helicenes by Lawesson’s reagent-mediated cyclization of helical quinone derivatives

New oxa[9]helicenes which possess one furan ring have been readily prepared by reactive helical quinone with Lawesson’s reagent or phosphorus pentasulfide in good yields. The versatility of this protocol has been demonstrated with various substituted helical quinones.     

Making and Breaking of C−N Bonds: Applications in the Synthesis of Unsymmetric Tertiary Amines and α-Amino Carbonyl Derivatives

An operationally simple process has been developed for the synthesis of unsymmetrical amines and α-amino carbonyl derivatives in the absence of a catalyst, ligand, oxidant, or any additives. Contrary to known reductive amination methods, this protocol is amenable to substrates containing other reducible groups. This process effectively results in consecutive cleavage and formation of C−N bonds. DFT studies and Hammett analysis provide useful insight into the mechanism. The role of noncovalent interactions as a stabilizing factor have been examined in the protocol. A wide range of alkyl-bromides have been coupled efficiently with a variety of dimethyl anilines to get unsymmetric tertiary amines with yields up to 90%. This methodology was further extended to the synthesis of α-amino carbonyl derivatives with yields up to 93%.     

Sequential Two-Fold Claisen Rearrangement,One-Pot Ring-Closing Metathesis and Cross-Metathesis as a Route to Substituted Benzo[b]azepine-2-one,Benzo[b]azepine and Benzo[b]oxepine Derivatives

A synthetic protocol involving sequential use of three atom-economic processes viz. Claisen rearrangement, ring-closing metathesis and cross metathesis has been developed to access 7-substituted benzo[b]azepine and benzo[b]oxepine derivatives starting from appropriate aniline or phenol in good overall yield. A one-pot RCM-CM protocol has also been developed for the synthesis of benzazepine and benzoxepine derivatives.     

Melamine as a Green and Reusable Catalyst for Knoevenagel Condensation at Room Temperature Under Solvent-Free Conditions

A rapid, efficient, and ecofriendly protocol has been developed for the Knoevenagel condensation of active methylene compounds such as malononitrile or ethyl cyanoacetate with aldehydes in the presence of melamine with good to excellent yields at room temperature without solvent.     

A facile two-step synthesis of 2-arylbenzofurans based on the selective cross McMurry couplings

A novel two-step synthesis of 2-arylbenzofurans has been developed. It involves a selective cross McMurry coupling of a salicylaldehyde or substituted salicylaldehyde with an aromatic aldehyde and a sequential oxidative cyclization of the resulting ortho-vinylphenols. Utilizing this synthetic protocol, a variety of 2-arylbenzofurans including cicerfuran have been efficiently synthesized.     

Iron-catalyzed Minisci acylation of N-heteroarenes with α-keto acids

An efficient and mild protocol has been developed for the Minisci acylation reactions of nitrogen-containing heteroarenes with α-keto acids. Distinct from the conventional Minisci acylation conditions, the chemistry was performed using non-noble metal Fe(II), instead of expensive Ag(I) salt, as catalyst. A wide range of substrates, including aliphatic or aromatic α-keto acids, as well as various N-heteroarenes, proved to be compatible with the protocol. Scale-up experiment also demonstrates the practicality of the approach.     

Quantitative profiling of SiGe/Si superlattices by time-of-flight secondary ion mass spectrometry: the advantages of the extended Full Spectrum protocol

The abundance of work on SiGe-based devices demonstrates the importance of the compositional characterization of such materials. However, Secondary Ion Mass Spectrometry (SIMS) characterization of SiGe layers often suffers from matrix effects due to the non-linear variation of ionization yields with Ge content. Several solutions have been proposed in order to overcome this problem, each having its own limitations such as a restricted germanium concentration range, or a weak sensitivity to dopants or impurities. Here, we studied the improvements brought by an alternative protocol: the extended Full Spectrum protocol, which states proportionality between the composition of the secondary ion beam and that of the actual material. Previous studies on this protocol showed that it was extremely precise and reproducible for Ge quantification in a permanent regime, because of minimized matrix effects. In this study we thus investigated its accuracy for the simultaneous quantitative depth profiling of both matrix elements (Si, Ge) and impurities (B, C or P) in strained SiGe/Si superlattices by comparing results with those from more classic protocols. The profiles provided by the extended Full Spectrum protocol were found to be accurate, and to exhibit better properties than classic protocols in terms of signal/noise ratio and signal stability, along with a slight enhancement in depth resolution.     

An efficient synthesis of enol phosphates via organic base-promoted addition of phosphites to 4-oxo-enoates

A TMG catalyzed, practical and efficient hydrophosphorylation of 4-oxo-enoates by diethyl or diphenyl phosphite has been described. This protocol allows a convenient access to a variety of enol phosphates under mild conditions in good yield with excellent stereoselectivity.     

Pyrrolidinones derived from (S)-pyroglutamic acid: penmacric acid and analogues

Alkylation reactions using alpha-halolactams or lactam enolates derived from bicyclic lactam templates can proceed with high endo- or exo- diastereoselectivity respectively. In the latter case, stereochemical correction by means of enolate generation and hindered phenol quench is possible with moderate efficiency. This protocol has been applied to the synthesis of protected penmacric acid and its analogues.     

Microwave-assisted N-debenzylation of amides with triflic acid

A new and facile microwave-assisted protocol for the debenzylation of N-benzylamides with triflic acid has been developed. Both secondary and tertiary aliphatic or aromatic amides are obtained in moderate to good yields.     

A convenient one-pot Negishi coupling of amino-heteroaryl chlorides and alkyl bromides

A simple Ni-catalysed cross-coupling protocol for amino-heteroaryl chlorides with alkylzinc reagents has been developed. The alkylzinc reagents can be commercially available dialkylzincs or alkylzinc halides, or can be conveniently generated in situ from diethylzinc and primary alkyl bromides in the presence of the same inexpensive Ni catalyst used to effect the subsequent coupling reaction.     

Highly regioselective synthesis of 1-aryl-3 (or 5)-alkyl/aryl-5 (or 3)-(N-cycloamino)pyrazoles

[Reaction: see text]. An efficient highly regioselective protocol for the synthesis of isomeric 1,3-diaryl (or 1-aryl-3-alkyl) and 1,5-diaryl (or 1-aryl-5-alkyl)-5 (or 3)-(N-cycloamino)pyrazoles has been reported by cyclocondensation of common alpha-oxoketene N,S-acetal precursors with arylhydrazines by variation of reaction conditions.     

Highly efficient copper-catalyzed N-arylation of nitrogen-containing heterocycles with aryl and heteroaryl halides

New (S)-pyrrolidinylmethylimidazole ligands (4a-c) have been readily synthesized in a straightforward fashion from least expensive starting materials in short steps in high yields. Relatively mild and highly efficient CuI-catalyzed N-arylation procedures for imidazoles with aryl and heteroaryl bromides or chlorides have been developed in the presence of 4a and Cs2CO3. It is important to note that the protocol could tolerate functional groups such as ester, nitrile, nitro, ketone, free hydroxyl, and free primary amine on the aryl halide. The protocol could also be applicable to other pi-electron-rich nitrogen heterocycles (pyrrole, pyrazole, indole, benzimidazole, and triazole), affording the N-arylazoles in good to excellent yields.     

Direct detection of carrier ampholytes in immobilized pH gradients using picric acid precipitation.

A protocol is described for monitoring the heterogeneity of end products of organic syntheses yielding amphoteric molecules containing two or more amino groups. This protocol was found to be a valuable aid in synthesis of carrier ampholytes for specific isoelectric focusing applications. This method does not depend on the ampholytes themselves to dictate the conditions under which they are analyzed. Carrier ampholytes have been found previously to be insoluble in picric acid and the insolubility property was not dependent upon the pI of individual ampholyte species. This insolubility property was exploited in the protocol. Immobilized pH gradients were used to focus the carrier ampholytes. Ampholytes were then visualized in situ by picric acid precipitation. The data shows that the protocol is useful for analyzing the results of chemical manipulations for enhancing the resolution of carrier ampholytes. A direct relationship was shown between carrier ampholyte heterogeneity as demonstrated by this protocol and the resolution of complex protein mixtures in isoelectric focusing gels. Picric acid formed visible precipitates with a variety of organic compounds which contained more than one amino group.     

Nano-Mgo-Catalyzed One-Pot Synthesis of Phosphonate Ester Functionalized 2-Amino-3-Cyano-4H-Chromene Scaffolds at Room Temperature

Abstract

A facile and efficient protocol for one-pot three-component synthesis of structurally diverse (2-amino-3-cyano-4H-chromen-4-yl)phosphonic acid diethyl esters from the reaction of salicylaldehydes, malononitrile (or ethyl cyanoacetate), and triethylphosphite using basic nanocrystalline MgO as catalyst in aqueous ethanolic medium at room temperature has been developed. Nano-MgO has been prepared using a simple sol-gel approach. Clean reaction profile, easy reusability of MgO nano-catalyst, mild reaction condition, good yields, and practical applicability are the major advantages of the present protocol.     

Tris(4-anisyl)phosphine as an Efficient and Practical Reagent for the Synthesis of (E)-2-Benzylidenesuccinates

Condensation of maleic anhydride or dimethyl maleate with benzylaldehydes controlled by tris(4‐anisyl)‐phosphine to synthesize dimethyl (E)‐2‐benzylidenesuccinates has been systematically investigated. The protocol gives the product with high stereoselectivity in moderate to good yields under mild conditions. A plausible mechanism has been proposed.     

A metal-complex-tolerant CuAAC 'click' protocol exemplified through the preparation of homo- and mixed-metal-coordinated [2]rotaxanes

A series of mono- and bis-metallated [2]rotaxanes has been prepared using a CuAAC 'click' protocol that is compatible with metal-coordinated building blocks and ligands; the methodology provides a general means for appending a metal ion or complex to an organic scaffold via Cu(I)-catalysed 'click' chemistry, even when the molecule contains redox-active or kinetically labile metals or vacant ligand sites.     

Highly stereo- and regioselective synthesis of (Z)-trisubstituted alkenes via 1-bromo-1-alkyne hydroboration-migratory insertion-Zn-promoted iodinolysis and Pd-catalyzed organozinc cross-coupling

Hydroboration of 1-bromo-1-alkynes with dibromoborane followed by addition of 3 or 4 equiv of Me2Zn provides an efficient and selective route to (Z)-2-alkenyldimethylboranes (3) or (Z)-2-alkenylmethylzincs (4), respectively, which have been successfully applied to one-pot Suzuki (B-I) or Negishi (Zn-I) coupling in some less demanding cases. However, in more demanding cross-coupling reactions, only the use of either (Z)-2-alkenyliodides (5) or the alkenylzincs prepared from lithiation and then zincation of 5 proves to be highly satisfactory (Zn-II or Zn-III protocol). On the contrary, the corresponding organoboron coupling under B-II or B-III protocol appears to be less satisfactory. Preliminary studies indicate that certain substituents proximal to trisubstituted alkenes seriously affect the course of the desired alkenylboron cross-coupling.