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An easy and straightforward procedure has been developed for the synthesis of highly enantioenriched pyrrolo[1,2-a]quinolines through a one-pot process that comprises a domino cyclopropane ring opening/aza-Michael/aldol reaction followed by acid-promoted lactamization. The key feature of the synthetic approach relies on the ability of conveniently functionalized cyclopropaneacetaldehydes to undergo organocatalytic activation by a chiral secondary amine that enables the catalytic generation of a donor–acceptor cyclopropane. This intermediate has the potential to undergo a ring opening that generates an electrophilic α,β-unsaturated iminium ion that subsequently reacts through the already mentioned domino sequence and in which stereochemical information is very efficiently transferred from the amine catalyst to the final products. Moreover, one of the alkoxycarbonyl moieties can be easily removed by standard hydrolysis/decarboxylation, providing access to the target adducts as single stereoisomers.

The asymmetric and catalytic Michael reaction between α-nitroesters and nitroalkenes has been studied in the presence of two bifunctional catalysts both containing the same absolute chirality at the carbon backbone. The reaction performed in similar conditions allows us to control the syn or anti selectivity of the Michael adduct obtaining good yields and high enantiocontrol in all cases.

An enantioselective unprecedented NHC-catalyzed benzoin reaction of aromatic and aliphatic aldehydes with alkyl alkynyl ketones including trifluoromethyl ketones is developed.

Benzopyrylium ylides generated in situ from 1-acetoxyisochroman-4-ones reacted with α,β-unsaturated aldehydes in the presence of a bifunctional secondary-amine/squaramide catalyst to furnish [5+2] cycloaddition products in good yield with high diastereo- and enantioselectivity. The reaction proceeds by dienamine activation and involves β,γ-functionalization of the enal. The dienamine intermediates showed exclusive β,γ-reactivity and provided direct access to compounds with the 8-oxabicyclo[3.2.1]octane framework. The ability of the bifunctional secondary-amine/squaramide catalyst to engage in hydrogen-bonding interactions with the ylide made it particularly effective in terms of both the yield and the stereoselectivity of the transformation.

The presented MeLi mediated intramolecular acyl transfer reaction gives access to a large scope of amino acid derivatives in moderate to good yields.

Unconjugated 2,5-dienals are more reactive substrates than the corresponding fully conjugated α,β,γ,δ-unsaturated aldehydes towards organocatalytic activation through trienamine intermediates.

Ethyl glyoxylate N-tosylhydrazone (IIa) is identified as an excellent sulfonyl anion surrogate in the DBU-catalyzed conjugate addition reaction with enones and enals for the synthesis of functionalized sulfones.

The synthesis of densely functionalized pyrroloisoquinolines (VIII) is reported, representing the core structure of various alkaloids.

A simple one-pot procedure was developed for [3+2]-cycloaddition reactions of α,β-unsaturated aldehydes, diethyl aminomalonate, and aromatic aldehydes in the presence of diphenyl[(2 S )-pyrrolidin-2-yl]methanol as catalyst. This reaction converts simple, commercially available, starting materials into densely functionalized polysubstituted pyrrolidines under mild conditions and in a fully stereoselective fashion. Moreover, the use of brine as the reaction medium has remarkable beneficial effects in preventing the formation of self-condensation byproducts, cutting the reaction time, and reducing the production of wastes.

We optimized the structure of a new family of chiral diarylprolinol-type organocatalysts with improved performances in conjugate addition reactions performed in water and proceeding under the iminium activation manifold. The principles behind the catalyst design were, firstly, the incorporation of a tertiary amino group at the 4-position of the pyrrolidine scaffold, which can facilitate the reaction by providing a basic site that favors deprotonation of the pronucleophile, and, secondly, a bulky diaryltrialkylsilyloxymethyl group maintained at the 2-position to control the iminium ion geometry and to provide the required steric bias for face stereoselection. The nature of this 4-dialkylamino group and the relative 2,4-configuration was optimized and the resulting catalyst proved its efficiency in the catalytic enantioselective cyclopropanation of α,β-unsaturated aldehydes using water as the reaction solvent. Moreover, the reaction was studied by computational methods, which indicated that the overall transformation proceeded through a cascade Michael/α-alkylation sequence, in which the first iminium-mediated Michael addition reaction was the rate-determining step and also the step at which stereochemical information was transferred from the catalyst to the products.

The reaction of α,β-unsaturated aldehydes with N-tosylaminoacetophenone (II) proceeds with moderate cis-selectivity but both diastereomers are obtained with high enantioselectivity.

A new efficient protocol for the stereocontrolled formation of various 3-substituted pyrrolidines is presented.

Donor–acceptor monosubstituted hydrazones participate as suitable reagents able to undergo an enantioselective formal diaza–ene reaction with α,β-unsaturated aldehydes under chiral secondary amine catalysis. This constitutes a new approach for the enantioselective conjugate addition of hydrazones to enals under metal-free conditions and leads to the formation of γ-hydrazono carboxylic acids after oxidation/[1,3]-H shift. The methodology is also useful for the synthesis of enantioenriched β-substituted α-keto-1,5-diesters by using the hydrazone moiety as a masked carbonyl group.

Starting from racemic material, a single diastereomer with high enantiomeric purity is formed via a dieneamine intermediate formed by the chiral secondary amine catalyst.

The title synthesis is the first example of a cascade reaction involving the dienamine/iminium manifold.

Enantiopure pyrazolidines, pyrazolines and pyrazolidinones have been accessed in a direct and efficient manner through an organocatalytic, enantioselective aza-Michael/hemiaminal formation cascade process from enals and N,N′-disubstituted hydrazides. The process takes place with high regio- and stereoselectivities and furnishes the target compounds in high overall yields by means of an operationally very simple methodology.

We have developed a highly efficient procedure for carrying out the catalytic enantioselective (3+2) cycloaddition between enals and stable azomethine ylides such as isoquinolinium and phthalizinium methylides. Under the optimized reaction conditions highly substituted chiral pyrroloisoquinolines and pyrrolophthalazines have been obtained in high yields and excellent diastereo- and enantioselectivities.

The method uses (II) as an excellent hydroxymethanimidoyl anion equivalent and a chiral secondary amine as organocatalyst.

Ring cleavage of the tetrazolothione moiety permits the enantioselective preparation of important organic and medical reagents such as oxazinimines, formamidines, ureas and isoureas.

The organocatalytic conjugate addition of different aldehydes to beta-nitroacrolein dimethyl acetal, generating the corresponding highly functionalized nitroaldehydes in high yields and with high stereoselectivities, has been studied in detail. These transformations have been achieved by using both readily available starting materials in a 1:1 ratio as well as commercially available catalysts at a 10 mol % catalyst loading. Furthermore, a very short and efficient protocol has been devised for the preparation of highly enantioenriched pyrrolidines containing two or three contiguous stereocenters starting from the obtained Michael adducts. 3,4-Disubstituted pyrrolidines have been obtained in a single step by Zn-mediated chemoselective reduction of the nitro group followed by intramolecular reductive amination, and trisubstituted homoproline derivatives have been prepared by means of an olefination reaction and a cascade process involving chemoselective reduction of the nitro group followed by a fully diastereoselective intramolecular aza- Michael reaction.

The ability of amino acids to catalyze dynamic kinetic asymmetric transformation (DYKAT) with excellent stereoselectivity is presented. The novel DYKAT process was applied in the proline-catalyzed one-step de novo synthesis of triketide- and deoxysugars, which were formed with excellent diastereoselectivity and up to 99% ee. The de novo synthesis is accomplished via an enzyme-like DYKAT process, which includes continuous amino acid-mediated racemization of the acceptor β-hydroxy aldehyde in combination with amino acid-catalyzed direct selective aldol addition.

An efficient, very simple and eco-friendly procedure has been developed for the synthesis of highly enantioenriched α-amino aldehydes by IBX-mediated oxidation of the corresponding β-amino alcohols. The procedure has beenapplied to a wide range of substrates with different side chains and protecting groups showing that the final aldehydes can be obtained in very high yields and with no racemization at the stereogenic center present in the starting compounds.

The linear amino acid-catalyzed direct asymmetric intermolecular aldol reaction is presented; simple amino acids such as alanine, valine, isoleucine, aspartate, alanine tetrazole 3 and serine catalyzed the direct catalytic asymmetric intermolecular aldol reactions between unmodified ketones and aldehydes with excellent stereocontrol and furnished the corresponding aldol products in up to 98% yield and with up to > 99% ee.