Domino Synthesis of 3-Alkyliden-2,3-Dihydro-4-Quinolones

Dual Role of Vinyl Sulfonamides as N -Nucleophiles and Michael Acceptors in the Enantioselective Synthesis of Bicyclic δ-Sultams

Organocatalytic Enantioselective Intramolecular (Hetero)Michael Additions in Desymmetrization Processes

Intramolecular Nitrone Cycloaddition of α-(Trifluoromethyl)styrenes. Role of the CF3 Group in the Regioselectivity

The intramolecular 1,3-dipolar cycloaddition of ortho-substituted 1,1,1-trifluoromethylstyrene-derived nitrones is described. Tricyclic fused isoxazolidines were obtained as major or exclusive products, in contrast to the case for nonfluorinated substrates, which rendered the bridged derivatives. This change in the regioselectivity was attributed to the electronic and, particularly, steric requirements of the trifluoromethyl group in comparison to the methyl group. It is worth mentioning that trifluoromethylstyrenes have been employed for the first time as dipolarophiles in a 1,3-dipolar intramolecular cycloaddition reaction, leading to the corresponding isoxazolidines bearing a quaternary …

Organocatalytic Enantioselective Friedel‐Crafts Alkylation Reactions of Pyrroles

Highly convergent total synthesis of (+)-anaferine and (−)-dihydrocuscohygrine

A unified and highly convergent total synthesis of anaferine and dihydrocuscohygrine alkaloids has been devised, taking advantage of the dual role of N-sulfinyl amines as nucleophilic nitrogen sources and chiral auxiliaries. A bidirectional cross metathesis reaction followed by a double intramolecular aza-Michael reaction led us to create the whole skeleton of the natural products in a very simple manner.

Double asymmetric intramolecular aza-Michael reaction: a convenient strategy for the synthesis of quinolizidine alkaloids.

A new methodology to access the quinolizidine skeleton in an asymmetric fashion was devised. It involves two consecutive intramolecular aza-Michael reactions of sulfinyl amines bearing a bis-enone moiety, in turn generated by a monodirectional cross metathesis reaction. The sequence, which takes place with excellent yields and diastereocontrol, was applied to the total synthesis of alkaloids lasubine I and myrtine.

Enantioselective Synthesis of Pyrrolizidinone Scaffolds through Multiple-Relay Catalysis

A triple-tandem protocol for the synthesis of the pyrrolizidinone skeleton has been devised. It involves a cross metathesis-intramolecular aza-Michael reaction-intramolecular Michael addition tandem sequence, starting from N-pentenyl-4-oxo-2-alkenamides and conjugated ketones. In the presence of two cooperative catalysts, namely the second-generation Hoveyda-Grubbs catalyst and (R)-TRIP-derived BINOL phosphoric acid, this multiple-relay catalytic process takes place in good yields and outstanding levels of diastero- and enantioselectivity with the simultaneous generation of three contiguous stereocenters.

Synthesis of substituted piperidines by enantioselective desymmetrizing intramolecular aza-Michael reactions.

An organocatalytic enantioselective intramolecular aza-Michael reaction has been described for the first time in a desymmetrization process employing substrates different from cyclohexadienones. By using 9-amino-9-deoxy-epi-hydroquinine as the catalyst and trifluoroacetic acid as a co-catalyst, a series of enantiomerically enriched 2,5-and 2,6-disubstituted piperidines have been obtained in good yields and with moderate diastereoselectivity. Depending on the catalyst/co-catalyst loading ratio, either the major or the minor diastereoisomer of the final piperidine products was achieved with high levels of enantioselectivity. Finally, some mechanistic insights have been considered by means of …

Two Decades of Progress in the Asymmetric Intramolecular aza-Michael Reaction.

The asymmetric intramolecular aza-Michael reaction (IMAMR) is a very convenient strategy for the generation of heterocycles bearing nitrogen-substituted stereocenters. Due to the ubiquitous presence of these skeletons in natural products, the IMAMR has found widespread applications in the total synthesis of alkaloids and biologically relevant compounds. The development of asymmetric versions of the IMAMR are quite recent, most of them reported in this century. The fundamental advances in this field involve the use of organocatalysts. Chiral imidazolidinones, diaryl prolinol derivatives, Cinchone-derived primary amines and quaternary ammonium salts, and BINOL-derived phosphoric acids account…

Organocatalytic enantioselective synthesis of 2,5,5-trisubstituted piperidines bearing a quaternary stereocenter. Vinyl sulfonamide as a new amine protecting group

An organocatalytic desymmetrizing intramolecular aza-Michael reaction with vinyl sulfonamides as nucleophilic nitrogen source has been devised for the synthesis of a new family of 2,5,5-trisubstituted piperidines bearing a quaternary sterocenter. The process takes place with excellent levels of enantioselectivity and moderate to good diastereoselectivity. The vinyl sulfonamide moiety can be removed by means of an ozonolysis reaction.

CCDC 1829500: Experimental Crystal Structure Determination

Related Article: Marta Guerola, Marcos Escolano, Gloria Alzuet-Piña, Enrique Gómez-Bengoa, Carmen Ramírez de Arellano, María Sánchez-Roselló, Carlos del Pozo|2018|Org.Biomol.Chem.|16|4650|doi:10.1039/C8OB01139G

CCDC 1839885: Experimental Crystal Structure Determination

Related Article: Cristina Mulet, Marcos Escolano, Sebastián Llopis, Sergio Sanz, Carmen Ramírez de Arellano, María Sánchez‐Roselló, Santos Fustero, Carlos del Pozo|2018|Adv.Synth.Catal.|360|2885|doi:10.1002/adsc.201800548

CCDC 1891128: Experimental Crystal Structure Determination

Related Article: Marcos Escolano, Marta Guerola, Javier Torres, Daniel Gaviña, Gloria Alzuet-Piña, María Sánchez-Rosello, Carlos del Pozo|2020|Chem.Commun.|56|1425|doi:10.1039/C9CC09113K