The discovery of a novel activation mode provided by organocatalysis is presented. It is demonstrated that the merger of optically active secondary amines and polyenals generates reactive trienamine intermediates, which readily participate in Diels-Alder reactions with different classes of dienophiles, hence, providing a facile entry to highly complex molecular frameworks with excellent stereocontrol. For the Diels-Alder reactions with 3-olefinic oxindoles, spirocyclic oxidoles are formed in high yields, and with enantioselectivities in the range of 94-98% ee. It is demonstrated, that some of these products can be transformed into the hexahydrofuro[2,3-b]indole fragment. The organocatalytic trienamine concept has been extended to also include Diels-Alder reactions of olefins substituted with cyanoacetates providing multifunctional cyclohexenes with three contiguous stereocenters in high yield and good stereocontrol. The novelty of this activation strategy lies within the perfect chirality relay over a distance of up to eight bonds. Moreover, we also present the first trienamine tandem reaction by combining trienamine catalysis with enamine activation. In addition to the experimental results, a detailed mechanistic survey is also provided including NMR spectroscopic studies and calculations of the reactive trienamine intermediates, rationalizing the origin of stereochemistry.

The mechanisms of the α-, β- and γ-functionalisations of aldehydes and α,β-unsaturated aldehydes by secondary amines are presented and discussed.

This study demonstrates the first formal asymmetric trans-dihydroxylation and trans-aminohydroxylation of alpha,beta-unsaturated aldehydes in an organocatalytic multibond forming one-pot reaction cascade. This efficient process converts alpha,beta-unsaturated aldehydes into optically active trans-2,3-dihydroxyaldehydes and trans-3-amino-2-hydroxyaldehydes with the aldehyde moiety protected as an acetal. The elaborated one-pot protocol proceeds via the formation of 2,3-epoxy and 2,3-aziridine aldehyde intermediates, which subsequently participate in a novel NaOMe-initiated rearrangement reaction leading to the formation of acetal protected trans-2,3-dihydroxyaldehydes and trans-3-amino-2-hydroxyaldehydes in a highly stereoselective manner. Advantageously, this multibond forming reaction cascade can be performed one-pot, thereby minimizing the number of manual operations and purification procedures required to obtain the products. Additionally, for the purpose of trans-aminohydroxylation of the alpha,beta-unsaturated aldehydes, a new enantioselective aziridination protocol using 4-methyl-N-(tosyloxy)benzenesulfonamide as the nitrogen source has been developed. The mechanism of the formal trans-dihydroxylation and trans-aminohydroxylation of alpha,beta-unsaturated aldehydes is elucidated by various investigations including isotopic labeling studies. Finally, the products obtained were applied in the synthesis of numerous important molecules.

A combined amino- and N-heterocyclic carbene (NHC)-catalyzed one-pot reaction sequence for the synthesis of simple enantioenriched β-hydroxy and β-amino esters using commercially available catalysts at low catalyst loadings has been developed. The desired products were obtained in high yield and excellent enantiopurity. The generation of quaternary stereocenters and application in gram-scale synthesis were also realized, with no requirements of inert or anhydrous reaction conditions, thus making this transformation a highly practical protocol.

Dedicated to Professor Albert Eschenmoser on the occasion of his 85th birthdayChiral diphosphines are the most frequently used ligands in asymmetric catalysis. [1] In contrast, chiral secondary phosphine oxides (SPOs) are little explored as ligands. While their chemical and physical properties are well known, their use in asymmetric catalysis is still in its infancy. [2] SPOs are stable molecules which exist in equilibrium between two tautomeric forms: [3] the preferred pentavalent phosphine oxide and the trivalent phosphinous acid. When two different substituents are attached to the phosphorus atom, a configurationally stable, P-chiral group results which can coordinate to metals either through the phosphorus atom or through the oxygen atom.To date, only a few examples of asymmetric catalytic reactions with chiral SPOs have been described.[2] Ph-(tBu)P(O)H, a monodentate P-chiral SPO gave approximately 80 % ee in the palladium-catalyzed allylic alkylation, [4] while over 90 % ee was obtained with P-chiral diamino phosphine oxides.[5] In asymmetric hydrogenation, Rh and Ir complexes of monodentate chiral SPO ligands gave only moderately active and selective catalysts (ee values up to 85 %). [2c, 6] We thought that these somewhat disappointing results might be due to an insufficient affinity of SPOs for Rh, Ir, or Ru centers, the typical metals used in asymmetric catalytic hydrogenations. Our idea was therefore to combine an SPO with a PR 2 substituent which should not only lead to stronger coordination to the metal center but also should give better defined complexes. To avoid cumbersome resolution procedures [2c, 6, 7] we used either a chiral backbone or a chiral substituent, so that the chiral SPO unit could be built up in diastereoselective reactions (Scheme 1).Herein we present results for selected members of two SPO-P ligand families based on a chiral ferrocenyl backbone and a menthyl substituent, respectively (Scheme 1). The first approach leads to ligands structurally similar to the well known Josiphos [8] (therefore called JoSPOphos) while the second gives menthyl derivatives (called TerSPOphos since other terpene moieties are feasible). Both ligand families are modular, allowing the ligand properties to be tuned by the choice of the R and R' groups. First tests showed that these novel ligands give excellent enantioselectivities and high turnover numbers for the hydrogenation of a variety of functionalized alkenes.Two routes were developed for the preparation of the JoSPOphos ligands (Scheme 2). In route 1 the phosphine group was introduced before the SPO group, starting from (R)-N,N-dimethyl-1-[(S)-2-bromoferrocenyl]ethylamine (3), obtained by lithiation/bromination of the (R)-Ugi amine.[9]The dimethylamino group was exchanged for the desired PR 2 group to give ferrocenyl phosphine bromides 4 with retention of configuration. JoSPOphos ligands 1 a-d were obtained by treating 4 a or 4 b with BuLi at low temperature, subsequent addition of the chosen dichlorophosphine, and finally hydrolysis with water...