Enantioselective synthesis of (+)-patulolide C via proline-catalyzed sequential α-aminooxylation and Horner-Wadsworth-Emmons olefination

The enantioselective total synthesis of (+)-patulolide C isolated from Penicillium urticae has been achieved from commercially available 9-decen-1-ol. Jacobsen’s kinetic resolution and sequential α-aminooxylation and Horner-Wadsworth-Emmons (HWE) olefination followed by Yamaguchi lactonization are used as the key reaction steps.     

A facile enantioselective synthesis of (S)-N-(5-chlorothiophene-2-sulfonyl)-β,β-diethylalaninol via proline-catalyzed asymmetric α-aminooxylation and α-amination of aldehyde

A high-yielding enantioselective synthesis of the bioactive (S)-N-(5-chlorothiophene-2-sulfonyl)-β,β-diethylalaninol (1), a Notch-1-sparing γ-secretase inhibitor metabolite (with EC₅₀ = 28 nM) effective in reduction of Aβ production in vivo, has been realized starting from readily available 3-pentanone. The key steps of the synthesis are proline-catalyzed α-aminooxylation and α-amination of aldehyde; the latter contributing an overall yield of 45.2% and 98% ee.     

A novel approach for the synthesis of α-aminonitriles using Mitsunobu’s reagent under solvent-free conditions

A highly efficient, one-pot, three-component, solvent-free protocol for the synthesis of α-aminonitriles starting from their corresponding carbonyl compounds, amines, using Mitsunobu’s reagent has been developed. Diversity of α-aminonitriles has been synthesized in good to excellent yields (80-99%) using various kinds of aldehydes/ketones and a variety of amines.     

cis-Selective synthesis of 2,5-disubstituted pyrrolidines

A concise approach to cis-2,5-disubstituted pyrrolidines is reported, which relies upon N-tert-butoxycarbonylmethyl substitution in a substrate derived from pyroglutamic acid. The method is especially noteworthy since a significant improvement in the conditions for a key Lawesson’s reaction have been established. Regioselective enolate generation and alkylation permits extension of the C-5 side chain.     

Enantioselective synthesis of (S,S)-ethambutol using proline-catalyzed asymmetric α-aminooxylation and α-amination

An efficient enantioselective synthesis of (S,S)-ethambutol, a tuberculostatic antibiotic, has been achieved in 99% ee via both proline-catalyzed α-aminooxylation and α-amination of n-butyraldehyde as the key step.     

Microwave-promoted one-pot synthesis of 4H-thiopyrans from α,β-unsaturated ketones via a three-component reaction

An efficient one-pot synthesis of substituted 4H-thiopyrans has been accomplished from a three-component reaction of α,β-unsaturated ketones, Lawesson’s reagent and alkynes under microwave irradiation.     

Stereoselective formal synthesis of aspergillide A

The stereoselective formal synthesis of aspergillide A (1), a cytotoxic 14-membered macrolide, is disclosed. The key intermediate, a trisubstituted tetrahydropyran core is prepared by SmI₂-induced intramolecular reductive cyclization as well as by using sequential α-aminooxylation, Horner-Wadsworth-Emmons olefination, and followed by Oxa-Michael cyclization. Other notable transformations in the synthesis include the use of Jacobsen’s hydrolytic kinetic resolution, esterification, ring-closing metathesis (RCM), and cross-metathesis (CM) reactions.     

Stereodivergent approach to Alzheimer's therapeutic agent (R)-(−) and (S)-(+)-arundic acid employing chiral 4-pentenol derivatives as building blocks

An efficient stereodivergent total synthesis of anti-Alzheimer agent (R)-(?) and (S)-(+)-arundic acid has been achieved from both chiral and nonchiral materials. This strategy features an efficient approach to separable diastereomeric C-2 chiral 4-pentenol intermediates employing proline catalysed asymmetric α-aminooxylation and [3,3] sigmatropic Claisen rearrangement are the highlights of present synthesis.     

A concise enantioselective synthesis of (+)-lentiginosine

A high yielding enantioselective synthesis of the indolizidine alkaloid, (+)-lentiginosine, has been described based on asymmetric aza-Cope rearrangement and the l-proline catalyzed α-aminooxylation of aldehydes. The strategy also makes use of ring-closing metathesis for the construction of piperidine core.     

An organo-catalytic approach to the enantioselective synthesis of (R)-selegiline

An efficient enantioselective synthesis of (R)-selegiline has been achieved by two routes, via proline-catalyzed α-aminooxylation as well as α-amination of phenylpropanaldehyde as the key step.     

Organocatalytic enantioselective formal synthesis of HRV 3C-protease inhibitor (1R,3S)-thysanone

A short and efficient organocatalytic enantioselective formal synthesis of HRV 3C-protease inhibitor (1R,3S)-thysanone is achieved in a nine-step with 98.7% enantiomeric excess, by employing l-proline-catalyzed asymmetric α-aminooxylation of aldehyde and Oxa-Pictet-Spengler cyclization as the key steps.     

A short synthesis of (+)-harzialactone A and (R)-(+)-4-hexanolide via proline-catalyzed sequential α-aminooxylation and Horner–Wadsworth–Emmons olefination of aldehydes

An efficient and short enantioselective synthesis of the antitumor marine metabolite, (+)-harzialactone A 1 and pheromone, (R)-(+)-4-hexanolide 2 using l-proline-catalyzed sequential α-aminooxylation and Horner–Wadsworth–Emmons olefination of the respective aldehydes is described.     

Asymmetric synthesis of naturally occurring nonenolide xyolide through cross metathesis and macrolactonization reaction

Asymmetric total synthesis of xyolide, a small ring macrolide is presented in this article. The synthesis is achieved through an ‘E’ selective cross metathesis (CM) reaction between two appropriate fragments followed by lactonization by Shiina method. One of the fragments containing 7S,8S,9R stereocenters of xyolide is accessed from n-nonanal by adopting an organocatalytic asymmetric α-aminooxylation, Z-selective Ando olefination, and substrate directed dihydroxylation reaction. The other fragments containing 4S stereocenter was prepared by ME-DKR (metal enzyme combined dynamic kinetic resolution) method.     

A short enantioselective synthesis of the antiepileptic agent, levetiracetam based on proline-catalyzed asymmetric α-aminooxylation

An efficient enantioselective synthesis of a new antiepileptic drug, levetiracetam is described, in high optical purity (>99.5% ee), using proline-catalyzed α-aminooxylation of n-butyraldehyde as the key step.     

Intramolecular reductive amination strategy to the synthesis of (R)-N-Boc-2-hydroxymethylmorpholine, N-(3,4-dichlorobenzyl)(R)-2-hydroxymethylmorpholine, and (R)-2-benzylmorpholine

A concise high yielding enantioselective synthesis of (R)-N-Boc-2-hydroxymethylmorpholine, N-(3,4-dichlorobenzyl)(R)-2-hydroxymethylmorpholine, and (R)-benzylmorpholine has been achieved by employing proline-catalyzed asymmetric α-aminooxylation of aldehyde and palladium-catalyzed intramolecular reductive amination of azido aldehyde as the key steps.     

The first stereoselective total synthesis of the Z-isomer of cytospolide E

A convergent and highly stereoselective total synthesis of the Z-isomer of cytospolide E has been achieved via Evan’s aldol reaction, Sharpless kinetic resolution and RCM cyclisation.     

A novel light induced Knoevenagel condensation of Meldrum’s acid with aromatic aldehydes in aqueous ethanol

A highly efficient environment-friendly photochemical methodology has been developed for the condensation of Meldrum’s acid with aromatic aldehydes in water-ethanol solution sans any catalyst, support or promoter.     

Solubility of freons in polar and non-polar liquids at 298.15 K

The cavity formation energy (CFE) is the free energy invested in rearrangement of the solvent molecules when a solute is inserted into a solvent, which is very important to the solubility studies. The CFE of liquid solvents; n-heptane, n-octane, cyclohexane, tetrachloromethane, benzene and water at 298.15 K has been determined. The solubility (in terms of Henry’s law constant), Gibb’s free energy of solution and ΔG_s^*, the thermodynamical quantities for the solvation process defined by Ben-Naim and Marcus of fluorine containing gases; freon-11, freon-12, freon-13, freon-14, freon-21, freon-c-318 and sulpherhexafluoride (SF₆) in above liquid solvents at 298.15 K also been calculated with this cavity formation energy. It yields good agreement with experimental results. The calculation shows importance of CFE in determining the solution properties.     

Enantioselective aza-Diels-Alder reaction of Brassard’s diene with aldimines catalyzed by chiral N,N′-dioxide-Yb(OTf)3 complex

The chiral N,N′-dioxide-Yb(OTf)₃ complex-catalyzed enantioselective aza-Diels-Alder reaction of Brassard’s diene with aldimines has been developed, giving the corresponding α,β-unsaturated δ-lactam derivatives in moderate yields with good enantioselectivities (up to 81% ee and up to 99% ee by single recrystallization) under mild conditions. Isolation of the reaction intermediate indicates that this asymmetric aza-Diels-Alder reaction proceeds through a stepwise Mannich-type pathway.     

Boolean and fuzzy logic implemented at the molecular level

In this work, it is shown how to implement both hard and soft computing by means of two structurally related heterocyclic compounds: flindersine (FL) and 6(5H)-phenanthridinone (PH). Since FL and PH have a carbonyl group in their molecular skeletons, they exhibit Proximity Effects in their photophysics. In other words, they have an emission power that can be modulated through external inputs such as temperature (T) and hydrogen-bonding donation (HBD) ability of solvents. This phenomenology can be exploited to implement both crisp and fuzzy logic. Fuzzy Logic Systems (FLSs) wherein the antecedents of the rules are connected through the AND operator, are built by both the Mamdani’s and Sugeno’s models. Finally, they are adopted as approximators of the proximity effect phenomenon and tested for their prediction capabilities. Moreover, FL as photochromic compound is also a multiply configurable crisp logic molecular element.