Albert Moyano

Highly Enantio‐ and Diastereoselective Organocatalytic Desymmetrization of Prochiral Cyclohexanones by Simple Direct Aldol Reaction Catalyzed by Proline

Panacea for aldol desymmetrizations: We describe an easy entry for the desymmetrization of 4-substituted-cyclohexanones catalyzed by proline, using as cocatalysts different hydrogen-bonding donors (see scheme), which dramatically improves the catalytic efficiency of proline in desymmetrization reactions.

Enantioselective Organocatalytic Addition of Oxazolones to 1,1-Bis(phenylsulfonyl)ethylene: A Convenient Asymmetric Synthesis of Quaternary α-Amino Acids

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.

Formal Highly Enantioselective Organocatalytic Addition of Fluoromethyl Anion to α,β-Unsaturated Aldehydes

Symmetric fluoromethylation made easy: a highly enantioselective fluoromethyl addition to ?,?-unsaturated aldehydes is described (see scheme). The synthesis of chiral fluorinated blocks, including ?-fluoro-?-aminoalcohol derivatives is disclosed.

Enantioselective Organocatalytic Addition of Azlactones to Maleimides: A Highly Stereocontrolled Entry to 2,2‐Disubstituted‐2H‐oxazol‐5‐ones

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.

Frank Model and Spontaneous Emergence of Chirality in Closed Systems

In a closed system an irreversible enantioselective autocatalysis coupled to a mutual inhibition reaction, corresponding to a fast and low exergonic formation of the heterochiral dimer which reverts to the monomers in the final reaction work-up, yields absolute asymmetric synthesis even in the absence of chiral polarizations. This is due to the very high chiral amplifications of the initial small statistical deviations from the ideal racemic composition. Moreover, this system is sensitive to very small chiral polarizations (energy differences between transition states below the mJ mol(-1) range). This behaviour can also be observed in reversible exergonic reactions, because the racemization time scale is substantially longer than that of the transformation of the initial reagents. The effect of the presence of other reactions likely to occur (i.e. non-catalytic transformations, non-enantioselective catalysis and homodimer formation) is discussed. Even if these decrease the sensitivity of the network in several chemical scenarios, the emergence of kinetically controlled spontaneous symmetry breaking is not hindered. These features, together with the response of the system to a sequential reaction procedure, suggest that a similar type of network is at the heart of the Soai reaction.

Substrate‐Dependent Nonlinear Effects in Proline–Thiourea‐Catalyzed Aldol Reactions: Unraveling the Role of the Thiourea Co‐Catalyst

The study of nonlinear effects in the proline–thiourea-catalyzed aldol reaction between acetone and aromatic aldehydes, together with NMR and ESI-MS experiments, shows that the main role of the thiourea co-catalyst is that of promoting both the formation of a soluble Seebachs oxazolidinone intermediate and its conversion into the iminium carboxylate isomer.

Regioselective ring opening of chiral epoxyalcohols by primary amines

Abstract A reinvestigation of the titanium(IV)-mediated reaction of primary amines with chiral 2,3-epoxyalcohols shows that, contrary to previous reports, this reaction constitutes a general and practical process for the enantioselective synthesis of 3-amino-1,2-diols.

Ready access to stereodefined β-hydroxy-γ-amino acids. Enantioselective synthesis of fully protected cyclohexylstatine

Abstract A convenient entry to enantiopure syn or anti β-hydroxy-γ-amino acids is described. The starting compounds for the synthesis, anti 3-amino-1,2-diols, are readily available in high enantiomeric purity through catalytic asymmetric epoxidation of an allylic alcohol and titanium-promoted oxirane opening. After adequate protection of the nitrogen, a stereodivergent sequence leads to both anti and syn N-Boc-aminoalkyl epoxides. Subsequent regioselective ring-opening with cyanide, protection of the resulting secondary alcohol and nitrile to carboxyl conversion afford, in good yields, protected β-hydroxy-γ-amino acids belonging to either the anti (erythro) or syn (threo) series. This methodology has been applied to the enantioselective preparation of cyclohexylstatine, a key component of several aspartyl protease inhibitors, in fully protected form.

Formal Highly Enantioselective Organocatalytic Addition of Alkyl Anions to α,β‐Unsaturated Aldehydes: Application to the Synthesis of Isotope‐Enantiomers

For the first time, organocatalytic addition of masked alkyl chains to ?,?-unsaturated aldehydes is reported (see scheme). The addition of bisphenylsulfonylmethane takes place in high yields and with excellent enantioselectivities. Furthermore, this methodology allows the synthesis of isotope-enantiomers.

Toward the understanding of the mechanism and enantioselectivity of the Pauson-Khand reaction. Theoretical and experimental studies*

Semiempirical and density functional theory (DFT) calculations have been performed on the key steps of the commonly accepted mechanism of the PausonKhand reaction (PKR). In this context, the high reactivity of ynamine complexes in the cycloaddition process has been rationalized on the basis of an anomerically assisted dissociation of CO. Moreover, an explanation has been provided for the correlation between olefin strain and reactivity in the PKR. Inspired by these results, new selective syntheses of cyclopentanones and phenols based on PKR with cyclopropene have been developed. On the other hand, the theoretical analysis of phosphine-substituted dicobalt carbonyl complexes of alkynes has helped in the development of efficient chelating (P,N) and bridging (P,S) ligands for the stereochemical control of the reaction and in the understanding of their action modes.