In recent years, organocatalysis has enhanced its importance as a tool for the synthesis of enantiomerically enriched compounds. Among the candidates for organocatalysis, the construction of asymmetric quaternary carbons is regarded as a challenging problem in organic synthesis. In particular, 3,3′-disubstituted oxindoles have one or more asymmetric quaternary carbon atoms and they represent a large family of bioactive compounds and synthetic derivatives that mimicry natural products. Therefore they are good targets for drug candidates and in the last two years many papers have appeared on organocatalytic methods for the synthesis of 3,3′-disubstituted oxindoles. Moreover, in the last few years 2-substituted and 2,2′-disubtituted 3-indolinones have also attracted the interest of chemists. This review aims to cover the literature on these topics from its origin to the end of 2011.

Recent advances in organocatalytic methods for the synthesis of disubstituted 2- and 3-indolinones

The combination of transition metal catalysis and organocatalysis as a new and exciting research area has attracted increasing attention as it can enable the development of unprecedented transformations that is not possible by use of either of the catalytic systems alone, and can improve the reactivity, efficiency and stereocontrol of existing chemical transformations. In this review, we summarize recent remarkable progress in the field of combined transition metal catalysis and organocatalysis, further highlighting the potential of this new and exciting research area and the many challenges that still remain for the future.

Combining transition metal catalysis and organocatalysis--an update.

Supramolecular catalysis is a rapidly expanding discipline which has benefited from the development of both homogeneous catalysis and supramolecular chemistry. The properties of classical metal and organic catalysts can now be carefully tailored by means of several suitable approaches and the choice of reversible interactions such as hydrogen bond, metal–ligand, electrostatic and hydrophobic interactions. The first part of these two subsequent reviews will be dedicated to catalytic systems for which non-covalent interactions between the partners of the reaction have been designed although mimicking enzyme properties has not been intended. Ligand, metal, organocatalyst, substrate, additive, and metal counterion are reaction partners that can be held together by non-covalent interactions. The resulting catalysts possess unique properties compared to analogues lacking the assembling properties. Depending on the nature of the reaction partners involved in the interactions, distinct applications have been accomplished, mainly (i) the building of bidentate ligand libraries (intra ligand–ligand), (ii) the building of di- or oligonuclear complexes (inter ligand–ligand), (iii) the alteration of the coordination spheres of a metal catalyst (ligand–ligand additive), and (iv) the control of the substrate reactivity (catalyst–substrate). More complex systems that involve the cooperative action of three reaction partners have also been disclosed. In this review, special attention will be given to supramolecular catalysts for which the observed catalytic activity and/or selectivity have been imputed to non-covalent interaction between the reaction partners. Additional features of these catalysts are the easy modulation of the catalytic performance by modifying one of their building blocks and the development of new catalytic pathways/reactions not achievable with classical covalent catalysts.

/pdf/supramolecular-catalysis-part-1-non-covalent-interactions-as-4sw3itqtq6.pdf

Supramolecular catalysis. Part 1: non-covalent interactions as a tool for building and modifying homogeneous catalysts.

In this “Emerging Area”, the strategic classification of one-pot catalysis, i.e. cooperative, relay and sequential catalysis, is described. In order to illustrate this classification, we take the readers through a series of recent examples which utilize either metal-metal, metal-organo and organo-organo catalysts. The compilation clearly demonstrates the explosive growth and power of this field, which has become, in the last few years, an important technique particularly in the case of enantioselective catalysis.

A one-pot catalysis: the strategic classification with some recent examples

Chiral metal–organic frameworks (MOFs) with porous and tunable natures have made them feasible for performing a variety of chemical reactions as heterogeneous asymmetric catalysts. By incorporating the oxidation catalyst [BW12O40]5– and the chiral group, l- or d-pyrrolidin-2-ylimidazole (PYI), into one single framework, the two enantiomorphs Ni-PYI1 and Ni-PYI2 were obtained via self-assembly, respectively. The channels of Ni-PYIs were enlarged through a guest exchange reaction to remove the cationic chiral templates and were well modulated with hydrophilic/hydrophobic properties to allow molecules of both H2O2 and olefin ingress and egress. The coexistence of both the chiral directors and the oxidants within a confined space provided a special environment for the formation of reaction intermediates in a stereoselective fashion with high selectivity. The resulting MOF acted as an amphipathic catalyst to prompt the asymmetric dihydroxylation of aryl olefins with excellent stereoselectivity.

Engineering Chiral Polyoxometalate Hybrid Metal–Organic Frameworks for Asymmetric Dihydroxylation of Olefins

This Minireview focuses on asymmetric reactions mediated by two distinct chiral catalysts (chiral multiple catalysis). Initially, this approach appears unconventional, but indeed it allows a fast multidimensional optimization and fine-tuning of the catalytic system required to perform a given transformation. Herein, this emerging concept is presented and its potential applications are highlighted.

Multiple catalysis with two chiral units: an additional dimension for asymmetric synthesis.

Biomimetic organocatalytic asymmetric synthesis of 2-substituted piperidine-type alkaloids and their analogues.

Synergic asymmetric organocatalysis (SAOc) of Cinchona alkaloids and secondary amines in the synthesis of bicyclo[2.2.2]octan-2-ones.

In diesem Kurzaufsatz werden asymmetrische Reaktionen vorgestellt, die durch zwei unterschiedliche chirale Katalysatoren vermittelt werden (chirale Mehrfachkatalyse). Diese zunachst eigenwillig anmutende Methode ermoglicht tatsachlich eine schnelle, mehrdimensionale Optimierung und Feinabstimmung des Katalysesystems, das zur Ausfuhrung einer bestimmten Umsetzung erforderlich ist. Hier werden dieses junge Konzept und seine moglichen Anwendungen erlautert.

Mehrfachkatalyse durch zwei chirale Einheiten: eine weitere Dimension in der asymmetrischen Synthese

The pyrrolo-isoquinoline moiety is present in alkaloid families such as erythrines, lamellarins, and pyrrolo ACHTUNGTRENNUNG[2,1a]isoquinoline derivatives, all of which exhibit biological activities. The importance of this heterocyclic system is further enhanced by its utility as an intermediate for the synthesis of alkaloids. Consequently, the interest in new synthetic methodologies for this moiety has increased. Three strategies have been developed for the asymmetric construction of polyhydropyrrolo ACHTUNGTRENNUNG[2,1-a]isoquinoline derivatives: a) N-acyliminium cyclization, b) Mitsunobu reaction of optically pure 3-(tetrahydroisoquinolin-1-yl)propan-1-oles, and c) asymmetric hydrogenation of prochiral iminium salts with a chiral metal complex. 9] A diastereoselective route to this moiety involving a [3+2]-cycloaddition of 3,4-dihydroisoquinolinium ylides to chiral dipolarophiles was recently presented. One strategy to optically active polysubstituted pyrrolidines is the metalor organocatalyzed [3+2]-cycloaddition of alkenes with azomethines. However, these reactions focus on a-iminoesters as azomethine ylide precursors and only recently has an organocatalytic [3+2]-cycloaddition of azomethine ylides to a,b-unsaturated aldehydes been presented. Herein we present a new multicomponent concept for the construction of hexahydropyrrolo ACHTUNGTRENNUNG[2,1-a]isoquinoline derivatives. The concept is based on a [3+2]-cycloaddition reaction of in situ generated dihydroisoquinolinium ylides, from the corresponding imines and a-bromoesters or ketone, to a,b-unsaturated aldehydes, and is catalyzed by a chiral pyrrolidine in the presence of a base (Scheme 1). This multicomponent approach allows the formation of two new C C bonds, a C N bond, and four stereocenters in one-step. The three-component reaction between 6,7-dimethoxy3,4-dihydroisoquinoline HCl (1 a), methyl 2-bromopropanoate (2 a), and cinnamic aldehyde (3 a) was the model system for optimization of the experimental parameters. (S)-2-(Diphenyl(trimethylsilyloxy)methyl)pyrrolidine (4 a), Na2CO3, CH2Cl2, and room temperature were the best conditions for the [3+2]-cycloaddition and gave the optically active product, as the conjugated ester 5 a, in high yields, good diastereoselectivity and an excellent enantioselectivity of 95 % ee. The scope of the three-component [3+2]-cycloaddition using different a,b-unsaturated aldehydes is given in Table 1.

Daniele M. Scarpino Schietroma

Papers

Multiple catalysis with two chiral units: an additional dimension for asymmetric synthesis.

Biomimetic organocatalytic asymmetric synthesis of 2-substituted piperidine-type alkaloids and their analogues.

Synergic asymmetric organocatalysis (SAOc) of Cinchona alkaloids and secondary amines in the synthesis of bicyclo[2.2.2]octan-2-ones.

Mehrfachkatalyse durch zwei chirale Einheiten: eine weitere Dimension in der asymmetrischen Synthese

Asymmetric synthesis of hexahydropyrrolo-isoquinolines by an organocatalytic three-component reaction.