Asymmetric organometallic and organocatalytic processes in aqueous systems are currently of great interest. A few years ago, only a few practitioners studied the subject; now organic reactions in water have become one of the most exciting research areas. The quest to identify water-compatible catalysts has evoked an intense search for new possibilities. Following nature's lead, the application of amino acids as sources of chiral information seems particularly promising for aqueous systems. Herein we provide an overview of very recent advances in the area of asymmetric catalysis in water with amino acids and their derivatives as effective catalysts or essential components of catalysts.

"I" did it: An iodine(III)-mediated bromocarbocyclization was elaborated as an efficient tool for the synthesis of oxoindoles. This method is applicable to a variety of structurally different substrates, also with chemically sensitive groups, and gives access to the heterocycles in a regio- and stereoselective fashion. The indole-2-ones obtained can be converted easily into structurally complex target compounds, such as the alkaloid physostigmine.

A combination of zinc triflate and chiral C 2 -symmetrical prolinamide ligand leads to high enantioselectivities in direct aldol reactions essentially assisted by water. The presence of 5 mol % of the catalyst affords an asymmetric intermolecular aldol reaction between unmodified ketones and aldehydes to give anti-products with excellent enantioselectivities ranging from 86-98 % ee. The same bis(prolinamide) ligand is found to catalyze the direct aldol reactions in the presence of water (or in water) with excellent stereocontrol and furnish the corresponding aldols in up to 99 % ee. For the demonstrated catalytic systems organic solvent-free conditions are applied.Keywords: aldol reaction; asymmetric synthesis; Lewis acids; organocatalysis; proline; water The ability to control the enantioselectivity of the aldol condensation has established this reaction as the principal chemical transformation for the stereoselective construction of complex polyol architectures. [1] However, most known methodologies require pre-activation of the nucleophilic or donor partner.[2] An exciting challenge to enhance the efficiency of the aldol reaction is to find a compound that will catalyze the direct aldol addition without prior stoichiometric formation of the substrate [3] as it takes place in biological-type catalysts, i.e., enzymes [4] and antibodies.[5]Pioneering studies by Shibasaki, [6] Trost, [7] List, [8] Barbas [9] and MacMillan [10] have outlined the first examples of enantioselective direct aldol reactions, an important class of organic and metal-catalyzed transformations that do not require the pre-generation of enolates or enolate equivalents.Reactions in which water is used as the solvent are another important issue and the development of enantioselective reactions in aqueous media is an extensively investigated topic. [11] In this regard, direct aldol reactions in water seem to be a challenging issue which needs to be intensively explored. In the nature, type I and II aldolases catalyze this reaction in water with excellent enantiocontrol through an enamine mechanism and by using a metal cofactor, respectively.[2b] The first reports of chemical organocatalysts for this process have just appeared. [12] In contrast, application of methods utilizing Lewis acids that rely on the catalysis of metal complexes bearing chiral ligands is troublesome in aqueous solvents. Mimicking the mode of action of class II aldolases, the homobimetalic Zn-BINOL complexes developed by Shibasaki [6c,d] as well as Trosts Zn-semi crown ethers [7] were reported to be water-sensitive and thus the reactions have been carried out under anhydrous conditions in organic solvents. Nevertheless, continuous exploration of zinc complexes seems to be rational as most aldolases contain an active site Zn(II) cofactor facilitating the enolate formation in water. [13] We have recently presented a chiral Zn(II) complex for Mukaiyama aldol reactions which proceed in aqueous organic solvent, [14] but this is an indirect method that requires pre-f...

The nucleophilicity of the substituents in iodobenzene pre-catalysts have a huge impact on product selectivity in iodine(III) triggered halogenations, steering the reactivity from solely carbocyclizations towards dihalogenations. Utilizing this catalyst-dependent reactivity a diastereo- and chemoselective dihalogenation method was established allowing the conversion of structurally and electronically diverse unsaturated compounds in excellent yields.

A tertiary hydroxy group α to a carboxyl moiety comprises a key structural motif in many bioactive substances. With the herein presented metal-free rearrangement of imides triggered by hypervalent λ(3)-iodane, an easy and selective way to gain access to such a compound class, namely α,α-disubstituted-α-hydroxy carboxylamides, was established. Their additional methylene bromide side chain constitutes a useful handle for rapid diversification, as demonstrated by a series of further functionalizations. Moreover, the in situ formation of an iodine(III) species under the reaction conditions was proven. Our findings clearly corroborate that hypervalent λ(3)-benziodoxolones are involved in these organocatalytic reactions.

A formal synthesis of a powerful cholesterol inhibitor, ezetymibe 1, is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from acetonide of L-glyceraldehyde and suitable C,N-diarylnitrone. The adduct with (3R,4S) configuration at the azetidinone ring, obtained with high stereoselectivity, was subsequently subjected to deprotection of the diol side chain followed by glycolic cleavage and base-induced isomerization at the C3 carbon atom to afford the (3S,4S) aldehyde, which has been already transformed into ezetimibe by the Schering-Plough group.

The marinopyrroles are a new class of natural products with highly interesting biomedical and structural features. We herein provide a concise, nitrogen‐protective‐group‐free synthesis of marinopyrrole A, constituting the as yet most efficient route. The presented studies elaborate a straightforward and mild chlorination protocol. Moreover, the first study towards the atropselective synthesis of marinopyrrole A, using chiral, C2‐symmetric bisthiourea catalysts, is presented.

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