Asymmetric enamine catalysis.

The legacy of Gilbert Newton Lewis (1875-1946) pervades the lexicon of chemical bonding and reactivity. The power of his concept of donor-acceptor bonding is evident in the eponymous foundations of electron-pair acceptors (Lewis acids) and donors (Lewis bases). Lewis recognized that acids are not restricted to those substances that contain hydrogen (Bronsted acids), and helped overthrow the "modern cult of the proton". His discovery ushered in the use of Lewis acids as reagents and catalysts for organic reactions. However, in recent years, the recognition that Lewis bases can also serve in this capacity has grown enormously. Most importantly, it has become increasingly apparent that the behavior of Lewis bases as agents for promoting chemical reactions is not merely as an electronic complement of the cognate Lewis acids: in fact Lewis bases are capable of enhancing both the electrophilic and nucleophilic character of molecules to which they are bound. This diversity of behavior leads to a remarkable versatility for the catalysis of reactions by Lewis bases.

Lewis Base Catalysis in Organic Synthesis

Transition metal-catalyzed enantioselective hydrogenation of enamides and enamines is one of the most important methods for the preparation of optically active amines. This review describes the recent developments of highly efficient catalytic asymmetric hydrogenation of enamides, and enamines. It specifically focuses on the substrates because hydrogenation of enamides and enamines is highly dependent on the substrates although the chiral metal catalysts play a significant role.

Transition Metal-Catalyzed Enantioselective Hydrogenation of Enamines and Imines

Asymmetric aldol reactions are a powerful method for the construction of carbon–carbon bonds in an enantioselective fashion. Historically this reaction has been performed in a stoichiometric fashion to control the various aspects of chemo-, diastereo-, regio- and enantioselectivity, however, a more atom economical approach would unite high selectivity with the use of only a catalytic amount of a chiral promoter. This critical review documents the development of direct catalytic asymmetric aldol methodologies, including organocatalytic and metal-based strategies. New methods have improved the reactivity, selectivity and substrate scope of the direct aldol reaction and enabled the synthesis of complex molecular targets (357 references).

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The Direct Catalytic Asymmetric Aldol Reaction

Catalytic enantioselective allylation of carbonyl compounds and imines.

The use of non covalent supramolecular ligand–ligand and ligand–substrate interactions in transition metal-catalysed transformations is a new, rapidly emerging area of research. Non-covalent interactions between monodentate ligands such as hydrogen bonding, coordinative bonding, ion pairing, π–π interactions and the formation of inclusion compounds, have been shown to impart higher activity and chemo-, regio-, and stereoselectivity to the corresponding transition metal complexes in a number of catalytic applications. Analogously, supramolecular ligand–substrate interactions, and particularly hydrogen bonding, have been used to direct the regio- and stereochemistry of several metal-catalysed reactions. The catalytic systems relying on supramolecular interactions are generally capable of self-assembling from simpler components in the environment where catalysis is to take place, and are therefore very well-suited for combinatorial catalyst discovery strategies and high-throughput screening.

Supramolecular ligand–ligand and ligand–substrate interactions for highly selective transition metal catalysis

Stereoselective reactions involving hypervalent silicate complexes

A series of structurally simple pyridine N-oxides have readily been assembled from inexpensive amino acids and tested as organocatalysts in the allylation of aldehydes with allyl(trichloro)silane to afford homoallylic alcohols. (S)-Proline-based catalysts afforded the products derived from aromatic aldehydes in fair to good yields and in up to 84% enantiomeric excess (ee). The allylation of heteroaromatic, unsaturated, and aliphatic aldehydes was less satisfactory. By running the reaction in the presence of achiral and chiral additives and structurally different catalysts, we collected some insights into the relationship between the stereochemical outcome and the catalyst's structural features. Even if the ee's obtained are inferior to the best values observed with other catalysts, this work concurs to show that structurally simple pyridine N-oxides can also promote the allylation reaction with satisfactory stereocontrol.

Structurally simple pyridine N-oxides as efficient organocatalysts for the enantioselective allylation of aromatic aldehydes.

The synthesis of multifunctional organic catalysts, easily obtained by the condensation of (S)-proline with 1,1′-binaphthyl-2,2′-diamine is reported. These C2 as well as C1 symmetric prolinamides were shown to be able to promote the direct aldol condensation between acetone, methoxyacetone or cyclohexanone and different aldehydes in very good yields and high enantioselectivities.

A multifunctional proline-based organic catalyst for enantioselective aldol reactions

A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (PhthalaPhos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97 % ee), methyl (Z)-2-acetamido cinnamate (6 ligands gave >94 % ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95 % ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1-yl)-acetamide (96 % ee in one case) and methyl (E)-2-(acetamidomethyl)-3-phenylacrylate (99 % ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.

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Luca Pignataro

Papers

Supramolecular ligand–ligand and ligand–substrate interactions for highly selective transition metal catalysis

Stereoselective reactions involving hypervalent silicate complexes

Structurally simple pyridine N-oxides as efficient organocatalysts for the enantioselective allylation of aromatic aldehydes.

A multifunctional proline-based organic catalyst for enantioselective aldol reactions

Rhodium-catalyzed asymmetric hydrogenation of olefins with PhthalaPhos, a new class of chiral supramolecular ligands.