An easy protocol has been developed for the formation of stereogenic carbon–fluorine centers by the organocatalytic asymmetric α‐fluorination of aldehydes 1. The 2‐fluoroaldehydes 4 are formed with 2 as the fluorinating agent and only 1 mol % of a sterically demanding silylated prolinol 3 as catalyst. The 2‐fluoroaldehydes are subsequently reduced to the corresponding alcohols 5 without loss of enantiomeric excess.

Cinchona alkaloids are employed in an organocatalyzed asymmetric Friedel–Crafts amination reaction of 2‐naphthols. These amination reactions proceed in high yields with up to 98 % ee and have led to a new class of non‐biaryl atropisomer. The rotation barriers of the chiral aminated 2‐naphthols have been investigated by experimental and computational methods.

The mechanism for the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes with electrophilic halogenation reagents has been investigated by using experimental and computational methods. These studies have led us to propose a mechanism for the reaction that proceeds through an initial N-chlorination of the chiral catalyst-substrate complex, followed by a 1,3-sigmatropic shift of the chlorine atom to the enamine carbon atom. The suggested reaction course is different from previously proposed mechanisms for organocatalytic enamine reactions, in which the carbon-electrophile bond is formed directly. Furthermore, the rate-determining step in the overall reaction was determined and the presence of nonlinear effects was probed.

The origin of the enantioselectivity in the TMS-protected (TMS=trimethylsilyl) prolinol-catalysed alpha-heteroatom functionalisation of aldehydes has been investigated by using density functional theory calculations. Eight different reaction paths have been considered which are based on four different conformers of the TMS-protected prolinol-enamine intermediate. Optimisation of the enamine structures gave two intermediates with nearly the same energy. These intermediates both have an E configuration at the C==C bond and the double bond is positioned anti or syn, relative to the 2-substituent in the pyrrolidine ring. For the four intermediates, the chiral TMS-protected-diaryl substituent effectively shields one of the faces of the reacting C==C bond in the enamine intermediate. A number of transition states have been calculated for the enantioselective fluorination by N-fluorobenzenesulfonimide (NFSI) and based on the transition-state energies it has been found that the enantioselectivity depends on the orientation of the C==C bond, being anti or syn, relative to the 2-substituent on the pyrrolidine ring, rather than the approach of the electrophilic fluorine to the face of the reacting carbon atom in the enamine which is less shielded relative to the face with the highest shielding. The calculated enantiomeric excess of 96 % ee (ee=enantiomeric excess) for the fluorination reaction corresponds well with the experimentally found enantiomeric excess-97 % ee. The transition state for the alpha-amination reaction with the same type of intermediate has also been calculated by using diethyl azodicarboxylate as the amination reagent. The implication of the intermediate structures on the stereoselection of alpha-functionalisation of aldehydes is discussed.

Ein einfacher Weg zu fluorsubstituierten Kohlenstoffstereozentren führt über die organokatalytische asymmetrische α‐Fluorierung der Aldehyde 1. Die 2‐Fluoraldehyde 4 werden mit 2 als Fluorierungsmittel und nur 1 Mol‐% des sterisch anspruchsvollen silylierten Prolinols 3 als Katalysator gebildet und anschließend ohne Verlust an Enantiomerenüberschuss zu den entsprechenden Alkoholen 5 reduziert.

The first catalytic asymmetric direct Mannich reaction of malonates and beta-keto esters has been developed. Malonates react with an activated N-tosyl-alpha-imino ester catalyzed by chiral tert-butyl-bisoxazoline/Cu(OTf)(2) to give the Mannich adducts in high yields and with up to 96% ee. These reactions create a chiral quaternary carbon center and it is demonstrated that this new direct Mannich reactions provides for example a new synthetic procedure for the formation of optically active beta-carboxylic ester alpha-amino acid derivatives. A series of different beta-keto esters with various ester substituents has been screened as substrates for the catalytic asymmetric direct Mannich reaction and it was found that the best results in terms of yield, diastereo- and enantioselectivity were obtained when tert-butyl esters of beta-keto esters were used as the substrate. The reaction of different beta-keto tert-butyl esters with the N-tosyl-alpha-imino ester gave the Mannich adducts in high yields, diastereo- and enantioselectivities (up to 95% ee) in the presence of chiral tert-butyl-bisoxazoline/Cu(OTf)(2) as the catalyst. To expand the synthetic utility of this direct Mannich reaction a diastereoselective decarboxylation reaction was developed for the Mannich adducts leading to a new synthetic approach to attractive optically active beta-keto alpha-amino acid derivatives. Based on the stereochemical outcome of the reactions, various approaches of the N-tosyl-alpha-imino ester to the chiral bisoxazoline/Cu(II)-substrate intermediate are discussed.

Chinaalkaloide werden für die organokatalysierte asymmetrische Friedel‐Crafts‐Aminierung von 2‐Naphtholen genutzt. Diese Aminierungen verlaufen in hohen Ausbeuten mit bis 98 % ee und haben zu einer neuen Klasse von Nicht‐Biaryl‐Atropisomeren geführt. Die Rotationsbarrieren der chiralen aminierten 2‐Naphthole wurden experimentell und mithilfe von Rechnungen untersucht.

The direct stereoselective addition of an activated imine to beta-keto phosphonates in the presence of chiral Lewis acid complexes is developed. The evaluation of different activated imines shows that an N-tosyl-alpha-imino ester adds in a diastereo- and enantioselective fashion to beta-keto phosphonates activated by especially chiral copper(II)-bisoxazoline complexes. An evaluation of Lewis acids, chiral ligands and reaction conditions, such as solvent, bases and other additives, shows that high yields, moderate diastereoselectivity and good enantioselectivity are obtained. The scope of the reaction is demonstrated for the reaction of beta-keto phosphonates and finally, the mechanism for the catalytic stereoselective step is presented.