José M. Sansano

Asymmetric intramolecular carbocyanation of alkenes by C-C bond activation.

Versatility: Ni(0) and Pd(0) complexes act as catalysts in the intramolecular aryl- and acylcyanation reactions, respectively, of alkenes (see scheme). These reactions not only proceed with high yield and selectivity, they also tolerate a wide range of functional groups and can furnish valuable heterocycles such as oxindoles, which are precursors for a myriad of natural and/or biologically active products.

1,3-Dipolar cycloadditions: applications to the synthesis of antiviral agents

In the present perspective the advances and real possibilities of 1,3-dipolar cycloadditions as key steps in the total synthesis of virus inhibitors are described. Azides, nitrones, and azomethine ylides are the most appropriate 1,3-dipoles for the synthesis of privileged structures with the highest biological responses against viruses.

Metal complexes versus organocatalysts in asymmetric 1,3-dipolar cycloadditions

Neste review apresentamos uma comparacao entre reacoes de cicloadicao 1,3-dipolar catalizadas por acido de Lewis com as organo catalizadas, com enfase na sintese enantiosseletiva de sistemas hetero ou carbociclicos de cinco membros. Essas reacoes exibem caracteristicas interessantes, mas a mais importante e a formacao de ate quatro centro estereogenicos em apenas uma etapa de reacao. In this review, a comparison between the Lewis acid catalysed and organocatalysed 1,3-dipolar cycloaddition is presented with special focus on the enantioselective synthesis of five-membered hetero- or carbocyclic systems, is described. These reactions exhibit very interesting features, but the most important one is the generation of up to four stereogenic centres in only one reaction step.

Enantioselective cyanoformylation of aldehydes mediated by BINOLAM–AlCl as a monometallic bifunctional catalyst

Abstract BINOLAM–AlCls, binaphthoxide aluminium chloride species generated in situ from either ( R )- or ( S )-3,3′-bis(diethylaminomethyl)-2,2′-dihydroxy-1,1′-binaphthalene (BINOLAM) behave as Lewis acid–Lewis base (LA-LB) catalysts in the enantioselective addition of methyl cyanoformate to aldehydes at room temperature, thereby leading to the asymmetric synthesis of ( S )- or ( R )- O -methoxycarbonyl cyanohydrins, respectively.

Phosphoramidite-Cu(OTf)2 complexes as chiral catalysts for 1,3-dipolar cycloaddition of iminoesters and nitroalkenes.

Chiral complexes formed by phosphoramidites such as (Sa,R,R)-9 and Cu(OTf)2 are excellent catalysts for the general 1,3-dipolar cycloaddition between azomethine ylides and nitroalkenes affording the corresponding tetrasubstituted proline esters mainly as exo-cycloadducts in high er at room temperature. The exo-cycloadducts can be obtained in enantiomerically pure form just after simple recrystallization. DFT calculations support the stereochemical results.

Glycine and Alanine Imines as Templates for Asymmetric Synthesis of α‐Amino Acids

The present paper is an overview of new methods for the asymmetric synthesis of different types of α-amino acids. These methods are based on alkylation and condensation reactions of glycine and alanine imine derivatives, which can be carried out under very mild and simple reaction conditions. The enolates generated from these types of reagents are very soft and can be alkylated in a highly diastereoselective manner, even at room temperature, by using chiral templates or asymmetric PTC conditions. These methodologies afford monoalkylated and dialkylated α-amino acids as well as heterocyclic derivatives. In the case of cyclic imine derivatives with oxazinone or pyrazinone structures, the condensation reaction under PTC conditions or with Eschenmoser’s salt allows the preparation of chiral α,β-didehydro-α-amino acid derivatives which can be hydrogenated, cyclopropanated or submitted to Diels−Alder cycloadditions to afford N-methylated and cyclic α-amino acids.

Enantioselective Cycloadditions of Azomethine Ylides

The asymmetric 1,3-DCR of azomethine ylides, which is generated from the corresponding imino ester and alkenes, is one of the most fascinating transformations because the configuration of the four new stereogenic centers of the finally obtained proline can be absolutely established in only one step with total atom economy. Since 2002, the catalyzed enantioselective 1,3-DCRs have been performed using chiral metal complexes. For example, chiral silver and copper complexes are the most employed catalysts. Silver complexes afforded selectively endo-cycloadducts, however, both exo- and endo-adducts were generated in the presence of several chiral Cu(I) complexes. Although chiral zinc complexes have also been studied in endo-selective processes, the published works are not so numerous. Bidentate ligands, such as bisphosphanes, nitrogenated phosphanes, and sulfur-containing phosphanes have shown very high enantioselectivity levels. Apart from the employment of chiral Lewis acids, the utilization of chiral bases or organocatalysts are also known, albeit with a large number of limitations and, in some cases, with lower enantioselections.

Enantioselective synthesis of (S)-α-methylphenylalanine using (S)-BINOLAMs as new phase-transfer catalysts

Abstract A series of (S)-bis(aminomethyl)binaphthols [(S)-BINOLAMs] 4 have been prepared and used as catalysts in the enantioselective C-alkylation reaction of the aldimine Schiff bases of alanine esters 5 under solid–liquid phase-transfer catalysis (PTC) conditions employing NaOH as base in toluene at room temperature. (S)-3,3′-Bis[(diethylamino)methyl]-2,2′-dihydroxy-1,1′-binaphthalene 4a gave the best e.e.s. (S)-α-Methylphenylalanine 7 was isolated, after hydrolysis of the iminoester, in 85% yield with an e.e. of 68%.

New chiral alanine template with a 1,2,3,6-tetrahydro-2-pyrazinone structure for the asymmetric synthesis of α-methyl α-amino acids

Abstract (R)-6-Isopropyl-5-phenyl-1,2,3,6-tetrahydro-2-pyrazinone, prepared from (R)-valine and (S)-alanine, reacts with activated alkyl halides and electrophilic olefins under solid–liquid PTC conditions with K2CO3 as base, at room temperature and with high diastereoselectivity (>94%). The palladium-catalyzed allylation reaction of this alanine derivative under neutral conditions at room temperature also takes place with a de>96%. Final hydrolysis of alkylated pyrazinones affords enantiomerically pure α-methyl α-amino acids.

β,γ-efoxy sulfones in organic synthesis. Part 2: Preparation of β,γ-bifunctionalized sulfones☆

Abstract Heteronucleophiles reagents react with β,γ-epoxy sulfones 1 at the γ-position in the presence of Ti(OPr i 4 or magnesium halides to afford regioselectively γ-functionalized β-hydroxy sulfones 2 . With soft nucleofiles such as sodium azide, triphenylphosphine, or sodium benzethiolate the reaction takes place in the absence of Lewis acids. In the case of basic reagents such as sodium metboxide or diethylamine the corresponding regioisomers, the β-functionalized γ-hydroxy sulfones 3 were exclusively obtained. The preparation of compounds 3 (R 2 =H) was also carried out starting from 3-tosyl-2-propen-1-ol ( 4 ) by Michael addition of different heteronucleophiles.