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.

Liquid chromatography-dielectric barrier discharge ionization mass spectrometry for the analysis of neutral lipids of archaeological interest.

Dielectric barrier discharge ionization has gained attention in the last few years due to its versatility and the vast array of molecules that can be ionized. In this study, we report on the assessment of liquid chromatography coupled to dielectric barrier discharge ionization with mass spectrometry for neutral lipid analysis. A set of different neutral lipid subclasses (triacylglycerides, diacylglycerides, and sterols) were selected for the study. The main species detected from our ionization source were [M-H2 O+H]+ , [M+H]+ or [M-R-H2 O+H]+ , attributed to sterol dehydration, protonation or the fragmentation of an acyl chain accompanied by a water loss of the glycerolipids, respectively. In terms of sensitivity, the dielectric barrier discharge displayed overall improved abundances and comparable or better limits of quantitation than atmospheric pressure chemical ionization for both acylglycerols and sterols. As a case study, different archaeological samples with variable content in neutral lipids, particularly triacylglycerides, were studied. The identification was carried out by combining accurate mass and the tentative formula associated with the exact mass, retention time matching with standards, and additional structural information from in-source fragmentation. The high degree of unsaturation and the presence of sterols revealed the potential vegetal origin of the material stored in the analyzed samples.

Synthesis of Allylic Amines by Asymmetric Transfer Hydrogenation of α,ß-Unsaturated N-(tert-Butylsulfinyl)imines.

Primary allylic amines with enantiomeric excesses from 97 to >99% were prepared by asymmetric transfer hydrogenation of α,ß-unsaturated N-(tert-butylsulfinyl)ketimines followed by removal of the sulfinyl group. The effect caused by different substituents at the C═C bond and at the iminic carbon atom on the chemoselectivity of the reduction was studied. The desired enantiomer of the final allylic amine can be synthesized by choosing the sulfinyl group with the appropriate absolute configuration.

Synthesis of nitrogenated heterocycles by asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines.

Highly optically enriched, protected, nitrogenated heterocycles with different ring sizes have been synthesized by a very efficient methodology consisting of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines followed by treatment with a base to promote an intramolecular nucleophilic substitution process. N-protected aziridines, pyrrolidines, piperidines, and azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and diastereomeric ratios up to >99:1. The free heterocycles can be easily obtained by a simple and mild desulfinylation procedure. Both enantiomers of the free heterocycles can be prepared with the same good results by changing the absolute configuration of the sulfur atom of the sulfinyl group.

Synthesis of γ-, δ-, and ε-lactams by asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters.

Highly enantiomerically enriched γ- and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spontaneous cyclization to the desired lactams during the basic workup procedure. Five- and six-membered ring lactams bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and ee's up to >99%. A slight modification of the procedure also allowed the preparation of ε-lactams in good yields and very high enantioselectivities. Both enantiomers of the final lactams could be prepared with equal efficiency by changing the absolute configuration of the sulfinyl chiral auxiliary.

Microwave-assisted solvent-free synthesis of enantiomerically pure N-(tert-butylsulfinyl)imines.

A simple, environmentally friendly, and very efficient procedure for the synthesis of optically pure N-(tert-butylsulfinyl)imines has been developed with microwave-promoted condensation of aldehydes and ketones using (R)-2-methylpropane-2-sulfinamide in the presence of Ti(OEt)(4), under solvent-free conditions. This procedure allows for the preparation of a variety of sulfinyl aldimines with excellent yields and purities in only 10 min, making any further purification of the imines unnecessary. Several sulfinyl ketimines have also been prepared in good yields by extension of the reaction times to 1 h. This methodology has proved to be equally efficient for the synthesis of aromatic, heteroaromatic, and aliphatic N-(tert-butylsulfinyl)imines. Conventional heating has also been shown to be useful to promote these reactions, especially for the synthesis of aldimines.

A versatile Ru catalyst for the asymmetric transfer hydrogenation of both aromatic and aliphatic sulfinylimines.

A highly efficient Ru catalyst based on an achiral, very simple, and inexpensive amino alcohol ligand (2-amino-2-methylpropan-1-ol) has been developed for the asymmetric transfer hydrogenation (ATH) of chiral N-(tert-butylsulfinyl)imines. This complex is able to catalyze the ATH of both aromatic and the most challenging aliphatic sulfinylimines by using isopropyl alcohol as the hydrogen source. The diastereoselective reduction of aromatic, heteroaromatic, and aliphatic sulfinylketimines, including sterically congested cases, over short reaction times (1-4 h), followed by desulfinylation of the nitrogen atom, affords the corresponding highly enantiomerically enriched (ee up to >99 %) α-branched primary amines in excellent yields. The same ligand was equally effective for the synthesis of both (R)- and (S)-amines by using the appropriate absolute configuration in the iminic substrate. DFT mechanistic studies show that the hydrogen-transfer process is stepwise. Moreover, the origin of the diastereoselectivity has been rationalized.

Asymmetric synthesis of chiral primary amines by transfer hydrogenation of N-(tert-butanesulfinyl)ketimines.

The diastereoselective reduction of (R)-N-(tert-butanesulfinyl)ketimines by a ruthenium-catalyzed asymmetric transfer hydrogenation process in isopropyl alcohol, followed by desulfinylation of the nitrogen atom, is an excellent method to prepare highly enantiomerically enriched alpha-branched primary amines (up to >99% ee) in short reaction times (1-4 h). (1S,2R)-1-Amino-2-indanol has been shown to be a very efficient ligand to perform this transformation. Ketimines bearing either an aryl or a heteroaryl group and an alkyl group as substituents of the iminic carbon atom are very good substrates for this process. The reduction of a dialkyl ketimine could also be achieved, affording the expected amine with moderate optical purity (69% ee). Some amines which are precursors of very interesting biologically and pharmacologically active compounds have been prepared in excellent yields and enantiomeric excesses.

Enantioselective Addition of Dialkylzinc Reagents to N-(Diphenylphosphinoyl) Imines Promoted by 2-Azanorbornylmethanols.

A set of new beta-amino alcohols 2, with the 2-azanorbornyl framework, has been prepared and evaluated as promoters for the enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinoyl) imines 1. By variation of the substitution pattern in the ligand, ee's up to 92% could be obtained. Although a stoichiometric amount of the ligand was used, about 90% of it could be recovered during the workup. Amino alcohol 2b, that gave the best enantioselectivities in the stoichiometric reaction, was also applied in a catalytic process, and ee's up to 85% were achieved using 0.25 equiv of the ligand, which is the highest ee obtained so far using that catalytic amount of the ligand. Addition products 3 could be converted into the free amines 4 without racemization by acidic hydrolysis. The utility of ligands 2 as catalysts in the addition of diethylzinc to benzaldehyde has also been investigated, and ee's up to 75% were achieved.

Preparation and Use of Aziridino Alcohols as Promoters for the Enantioselective Addition of Dialkylzinc Reagents to N-(Diphenylphosphinoyl) Imines.

A set of chiral aziridino alcohols 2-5 has been synthesized starting from either readily available amino acids (L-serine, L-threonine, and allo-L-threonine) or simple olefins (using Sharpless asymmetric aminohydroxylation and dihydroxylation reactions). Chiral ligands 2-5 have been tested as promoters for the enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinoyl) imines 1. The influence of the substituents on the aziridine ring and the alcohol moiety on the selectivity has been studied, and in the best case, an enantiomeric excess of up to 94% could be obtained. Acidic hydrolysis of the initially formed N-protected amines 6 led to the corresponding free amines 7 without racemization. Although a stoichiometric amount of the ligand was used, about 90% of it could be recovered during the workup and reused without significant loss of chiral induction. The utility of the aziridino alcohols 2-5 as catalysts for the same reaction has also been evaluated and enantiomeric excesses of up to 76% were achieved using 0.25 equiv of the chiral ligand. A possible transition state for the addition reaction is also proposed.