Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry.

In the presence of different nucleophilic Knoevenagel competitors, cyclic and acyclic ketones have been shown to undergo highly chemoselective aldol reactions with aldehydes. In doing so, the substrate breadth for this emerging methodology has been significantly broadened. The method is also no longer beholden to proline-based catalyst templates, e.g., commercially available O-t-Bu-L-threonine is advantageous for acyclic ketones. The key insight was to exploit water-based mediums under conventional (in-water) and non-conventional (deep eutectic solvents) conditions. With few exceptions, high aldol-to-Knoevenagel chemoselectivity (>10:1) and good product profiles (yield, dr, and ee) were observed, but only in DESs (deep eutectic solvents) in conjunction with ball milling did short reaction times occur.

Organocatalytic Enantioselective α-Nitrogenation of α,α-Disubstituted Aldehydes in the Absence of a Solvent.

A highly efficient enantioselective α-nitrogenation method of α,α-disubstituted aldehydes with azodicarboxylates promoted by a chiral carbamate-monoprotected cyclohexa-1,2-diamine as organocatalyst has been developed. The process was carried out without any solvent, and the corresponding α,α-disubstituted α-nitrogenated aldehydes were obtained with excellent yields and enantioselectivities up to 99% ee. The sustainability of the procedure was established through the calculation of green metrics, such as EcoScale and E-factor. In addition, theoretical calculations have been used to justify the obtained enantioselectivity sense.

Visible-light-mediated decarboxylative (E)-alkenylation of aliphatic carboxylic acids with aryl styryl sulfones under metal-free conditions.

The decarboxylative alkenylation of aliphatic carboxylic acids with aryl styryl sulfones is efficiently catalyzed by riboflavin tetraacetate under visible light irradiation at room temperature. This metal-free protocol is cost-efficient, environmentally friendly and provides the corresponding olefins with excellent (E)-diastereocontrol. The methodology can also be used to prepare internal alkynes regioselectively by using alkynyl sulfones as radical acceptors. The suitability as building blocks of the olefins obtained was demonstrated by performing an (E)- to (Z) photoisomerization, an iron-catalyzed allylic substitution of the phenoxy group derived from the 2-phenoxycarboxylic acid substrates, as well as syn-epoxidations, and diastereoselective intramolecular iodoarylations. Based on control experiments and DFT calculations, we proposed a reaction mechanism that accounts for the regio- and diastereo-selectivity observed.

Special Issue "Feature Review Papers in Organic Synthesis".

Organic synthesis allows scientists to construct and modify organic compounds using a continuously growing arsenal of reactions and methodologies [...].

Visible Light-Induced Aerobic Oxidative Dehydrogenation of C-N/C-O to C=N/C=O Bonds Using Metal-Free Photocatalysts: Recent Developments.

Performing synthetic transformation using visible light as energy source, in the presence of a photocatalyst as a promoter, is currently of high interest, and oxidation reactions carried out under these conditions using oxygen as the final oxidant are particularly convenient from an environmental point of view. This review summarizes the recent developments achieved in the oxidative dehydrogenation of C-N and C-O bonds, leading to C=N and C=O bonds, respectively, using air or pure oxygen as oxidant and metal-free homogeneous or recyclable heterogeneous photocatalysts under visible light irradiation.

Asymmetric Conjugate Addition of Ketones to Maleimides Organocatalyzed by a Chiral Primary Amine-Salicylamide.

Enantioenriched substituted succinimides are interesting compounds, and their asymmetric organocatalytic synthesis by the conjugated addition of ketones to maleimides has been scarcely explored. This study shows the enantioselective conjugate addition of ketones to maleimides organocatalyzed by a simple primary amine-salicylamide derived from a chiral trans-cyclohexane-1,2-diamine, which provides the desired succinimides in good to excellent yields (up to 98%) and with moderate to excellent enantioselectivities (up to 99%).

Synthesis of Xanthones, Thioxanthones and Acridones by a Metal-Free Photocatalytic Oxidation Using Visible Light and Molecular Oxygen.

9H-Xanthenes, 9H-thioxanthenes and 9,10-dihydroacridines can be easily oxidized to the corresponding xanthones, thioxanthones and acridones, respectively, by a simple photo-oxidation procedure carried out using molecular oxygen as oxidant under the irradiation of visible blue light and in the presence of riboflavin tetraacetate as a metal-free photocatalyst. The obtained yields are high or quantitative.

Special Issue: Development of Asymmetric Synthesis.

Biological systems usually respond differently to enantiomers of a chiral molecule due to the inherent chirality of the active receptor sites of enzymes in nature [...].

Organocatalytic Asymmetric Conjugate Addition of Aldehydes to Maleimides and Nitroalkenes in Deep Eutectic Solvents.

A chiral primary amine-salicylamide is used as an organocatalyst for the enantioselective conjugate addition of α,α-disubstituted aldehydes to maleimides and nitroalkenes. The reactions are performed in deep eutectic solvents as reaction media at room temperature, leading to the corresponding adducts with enantioselectivities up to 88% (for maleimides) and 80% (for nitroalkenes). Catalyst and solvent can be recovered and reused.

Asymmetric Conjugate Addition of α,α-Disubstituted Aldehydes to Nitroalkenes Organocatalyzed by Chiral Monosalicylamides from trans-Cyclohexane-1,2-Diamines.

Primary amine-salicylamides derived from chiral trans-cyclohexane-1,2-diamines are used as organocatalysts for the enantioselective conjugate addition of α,α-disubstituted aldehydes to arylated and heteroarylated nitroalkenes. The reaction is performed in the presence of 4-dimethylaminopyridine as an additive in dichloromethane as a solvent at room temperature. The corresponding enantioenriched γ-nitroaldehydes are obtained with enantioselectivities up to 95%. Theoretical calculations are used to justify the reasons of the stereoinduction.

Enantioselective Michael Addition of Aldehydes to Maleimides Organocatalyzed by a Chiral Primary Amine-Salicylamide.

A primary amine-salicylamide derived from chiral trans-cyclohexane-1,2-diamine was used as an organocatalyst for the enantioselective conjugate addition of aldehydes, mainly α,α-disubstituted to N-substituted maleimides. The reaction was performed in toluene as a solvent at room temperature. The corresponding enantioenriched adducts were obtained with high yields and enantioselectivities up to 94%. Theoretical calculations were used to justify the stereoinduction.

Special Issue: Asymmetric Synthesis 2017.

The use of asymmetric synthetic methodologies plays a crucial role, nowadays, in the preparation of bioactive or other interesting compounds [...].

Recent Advances in Asymmetric Organocatalyzed Conjugate Additions to Nitroalkenes.

The asymmetric conjugate addition of carbon and heteroatom nucleophiles to nitroalkenes is a very interesting tool for the construction of highly functionalized synthetic building blocks. Thanks to the rapid development of asymmetric organocatalysis, significant progress has been made during the last years in achieving efficiently this process, concerning chiral organocatalysts, substrates and reaction conditions. This review surveys the advances in asymmetric organocatalytic conjugate addition reactions to α,ß-unsaturated nitroalkenes developed between 2013 and early 2017.

Recent advances in Sonogashira reactions.

The coupling of aryl or vinyl halides with terminal acetylenes catalysed by palladium and other transition metals, commonly termed as Sonogashira cross-coupling reaction, is one of the most important and widely used sp(2)-sp carbon-carbon bond formation reactions in organic synthesis, frequently employed in the synthesis of natural products, biologically active molecules, heterocycles, molecular electronics, dendrimers and conjugated polymers or nanostructures. This critical review focuses on developments in the Sonogashira reaction achieved in recent years concerning catalysts, reaction conditions and substrates (352 references).

Determination of the Absolute Configuration of Amines and alpha-Amino Acids by (1)H NMR of (R)-O-Aryllactic Acid Amides.

(R)-O-Aryllactic acid (ROAL) amides derived from alpha-chiral primary amines and alpha-amino acid esters show different chemical shifts in (1)H NMR spectroscopy (300 MHz) depending on their configuration. Molecular mechanics, semiempirical calculations, and (1)H NMR studies suggest that, in solution, these amides prefer an ap-Z conformation with the C(alpha)OAr and C=O groups close to anti-periplanar as in the case of mandelic acid amides. The proposed conformational preference is different from that of the ROAL esters (C(alpha)H and C=O groups in a syn-periplanar conformation). The conformational model for ROAL amides allows the absolute configuration assignment of primary amines and alpha-amino acid esters according to the relative position of the aryl group and the substituents on the amine moiety, and also their enantiomeric composition.

Polymer-supported Cinchona alkaloid-derived ammonium salts as recoverable phase-transfer catalysts for the asymmetric synthesis of alpha-amino acids.

Alkaloids such as cinchonidine, quinine and N-methylephedrine have been N-alkylated using polymeric benzyl halides or co-polymerized and then N-alkylated, thus affording a series of polymer-supported chiral ammonium salts which have been employed as phase-transfer catalysts in the asymmetric benzylation of an N-(diphenylmethylene)glycine ester. These new polymeric catalysts can be easily recovered by simple filtration after the reaction and reused. The best ee's were achieved when Merrifield resin-anchored cinchonidinium ammonium salts were employed.

2,7-Di-tert-butyl-Fmoc-P-OSu: a new polymer-supported reagent for the protection of the amino group.

The polymer-supported (2,7-di-tert-butyl-9-fluorenyl)methyl succinimidyl carbonate (Dtb-Fmoc-P-OSu), derived from (2,7-di-tert-butyl-9-fluorenyl)methyl chloroformate (Fmoc-Cl) and a polymeric N-hydroxysuccinimide (P-HOSu), has been used for the preparation of Dtb-Fmoc-protected amines and amino acids. After the N-protection reaction, the liberated P-HOSu can be recovered and reused. This Dtb-Fmoc-protection improves the solubility of the Fmoc-protected analogues.