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The aldol reaction between acetone and 4-nitrobenzaldehyde run in the nominal absence of any enantioselective catalyst was monitored by chiral HPLC with the aid of an internal standard. The collected data show the presence of a detectable initial enantiomeric excess of the aldol product in the early stages of the reaction in about 50 % of the experiments. Only a small fraction of the reaction contained the non-racemic aldol product after 24 h. This temporary emergence of natural optical activity could be the signature of a coupled reaction network that leads to a spontaneous mirror-symmetry-breaking process, which originates at very low conversions (i.e., strongly depends on events taking place at the very first stages of the process). The reaction is not autocatalytic in the aldol product, which rules out a simple Frank-type reaction network as the source of the observed symmetry breaking. On the other hand, the isolation and characterisation of a double-aldol adduct suggested a reaction network that involved both indirect autocatalysis and indirect mutual inhibition between the enantiomers of the reaction product.

The catalytic enantioselective addition of 2-tert-butyl-4-aryl-1,3-oxazol-5-ones to maleimides is reported. The addition takes place exclusively at the C-4 position of the oxazolone ring, giving access to quaternary amino acid derivatives. The reaction is catalyzed by readily available chiral bases such as (DHQD)2PYR, rendering the final compounds in good yields and with moderate to good diastereo- and enantioselectivities. When the C-4-substituent of the 2-tert-butyl-oxazolone is an alkyl group, the regioisomeric C-2 addition product is also obtained.

The synthesis of piperidines and piperidines derivatives in enantiopure fashion has been a challenging goal for organic chemists. In this report we developed a nice cascade reaction for piperidine derivatives based in an amidomalonate Michael addition to enals followed by an intramolecular hemiaminal formation with good yields and enantioselectivities. Moreover we studied the ‘in situ’ intramolecular cyclization of this hemiaminals with alcohols forming fused piperidine–oxazolidines.

The first highly diastereo- and enantioselective organocatalytic synthesis of 2,2-disubstituted-2H-oxazol-5-ones is described. The addition of oxazolones to maleimides is promoted by bifunctional thiourea catalysts, which afford the corresponding 2,2-disubstituted-2H-oxazol-5-ones with total regio- and stereocontrol.

In spite of the tremendous growth experienced by the field of asymmetric organocatalysis in the last decade, it is important to realize that we are still far away from having explored all of the possible pathways in organocatalysis ‘territory'; the application of the organocatalysis concept can still provide new catalysts and reactions for a variety of asymmetric organic transformations. To exemplify this assertion, we summarize the research performed in our laboratory over the past two years which has led to the development of new enantioselective approaches to organometallic compounds, to the desymmetrization of prochiral ketones, to functionalized cyclopropanes and piperidines, to fluorinated compounds, and to quaternary ?-amino acids, among others.

A highly enantioselective organocatalytic synthesis of piperidines is reported. The reaction is catalyzed by simple and commercially available secondary amines, affording the corresponding adducts with high yields and enantioselectivities. Moreover, this reaction is used for the formal synthesis of (−)-Paroxetine, a blockbuster drug, in only three steps.

The first examples of highly enantioselective organocatalytic Mannich reactions of ferrocenecarbaldehyde are disclosed. The reaction is catalyzed by simple amino acids and gives access to β-arylamino-β-ferrocenylketones in high yields and with up to 99% ee.

Solvent effects in the L-tryptophan-catalyzed Mannich reaction between hydroxyacetone and glyoxylate imines have been examined. The use of a DMSO/1-butanol (4:1 v/v) mixture as solvent at rt provided the expected Mannich adducts in good yields, high anti-diastereoselectivity (up to 10.3:1 anti/syn ratio) and excellent enantioselectivities (up to >99.9% ee for the anti isomer).

Organocatalyzed Michael addition of amidomalonates, e.g. (I) and (VI), towards enals (II) followed by intramolecular hemiaminal formation provides enantioenriched piperidine derivatives (III) and (VII), resp., in up to 99% optical purity.

The highly enantioselective asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with bis(phenylsulfonyl)methane is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and enantioselectivities.

The enantioselective synthesis of fluorinated molecules has drawn much attention within the chemical community due to its unique stereoelectronic properties. The main aim of this review is to cover the most important organocatalytic enantioselective methodologies to obtain them. The review is divided into three parts: first, the direct introduction of a fluorine atom studied in the early 2000s. Second, the later use of Michael reactions to introduce fluorine-containing synthons. Finally, the simultaneously-developed trifluoromethylation reactions, giving the catalysts, mechanisms and reagents that have been used.

The enantioselective synthesis of fluorinated molecules has drawn much attention within the chemical community due to its unique stereoelectronic properties. The main aim of this review is to cover the most important organocatalytic enantioselective methodologies to obtain them. The review is divided into three parts: first, the direct introduction of a fluorine atom studied in the early 2000s. Second, the later use of Michael reactions to introduce fluorine-containing synthons. Finally, the simultaneously-developed trifluoromethylation reactions, giving the catalysts, mechanisms and reagents that have been used.

A new, practical and enantioselective entry to direct precursors of quaternary α-alkyl-α-amino acids is developed.

The first highly diastereo- and enantioselective organocatalytic synthesis of 2,2-disubstituted-2H-oxazol-5-ones is described. The addition of oxazolones to maleimides is promoted by bifunctional thiourea catalysts, which afford the corresponding 2,2-disubstituted-2H-oxazol-5-ones with total regio- and stereocontrol.

In spite of the tremendous growth experienced by the field of asymmetric organocatalysis in the last decade, it is important to realize that we are still far away from having explored all of the possible pathways in organocatalysis ‘territory'; the application of the organocatalysis concept can still provide new catalysts and reactions for a variety of asymmetric organic transformations. To exemplify this assertion, we summarize the research performed in our laboratory over the past two years which has led to the development of new enantioselective approaches to organometallic compounds, to the desymmetrization of prochiral ketones, to functionalized cyclopropanes and piperidines, to fluorinated compounds, and to quaternary ?-amino acids, among others.

A new, easy, and highly enantioselective method for the synthesis of quaternary α-alkyl-α-amino acids based on organocatalysis is described.

A new, easy, and highly enantioselective method for the synthesis of quaternary alpha-alkyl-alpha-amino acids based on organocatalysis is reported. The addition of oxazolones to 1,1-bis(phenylsulfonyl)ethylene is efficiently catalyzed by simple chiral bases or thioureas. The reaction affords alpha,alpha-disubstituted alpha-amino acid derivatives with complete C4 regioselectivity and with excellent yields and enantioselectivities. This methodology is complementary to previously reported enantioselective approaches to quaternary alpha-amino acids and allows the synthesis of alpha-phenyl-alpha-alkyl-alpha-amino acids and alpha-tert-butyl-alpha-alkyl-alpha-amino acids. It has distinct advantages in terms of operational simplicity, enviromentally friendly conditions, and suitability for large-scale reactions.

A highly enantioselective organocatalytic synthesis of piperidines is reported. The reaction is catalyzed by simple and commercially available secondary amines, affording the corresponding adducts with high yields and enantioselectivities. Moreover, this reaction is used for the formal synthesis of (−)-Paroxetine, a blockbuster drug, in only three steps.