Browsing by Author "Duefert, Alexander"

The synthesis of cephalotaxine- and cephalotaxine amide analogues 14a-c and 16a-c as well as of the deoxyharringtonine analogues 5a,b was performed employing a trimethylaluminium-mediated domino reaction of 9a-c and 8 to give the spirocyclic compounds 7a-c, which was followed by a palladium catalyzed alpha-arylation. (c) 2007 Published by Elsevier Ltd.

The efficient synthesis of natural products, drugs, and materials with economical and ecological advantages is a very important goal in modern synthetic chemistry. In such an approach, toxic substrates as well as reagents have to be avoided, the amount of waste has to be reduced, and the exploitation of our resources has to be diminished. In this respect, the use of catalytic processes is highly advantageous; however, even more beneficial is the combination of several catalytic processes either in a sequential or, more efficiently, in a domino mode. In this article, the synthesis of several natural products, drugs, and materials is described, employing multiple Pd-catalyzed processes either in a sequential or a domino fashion. Based on a double-Heck reaction developed by us for the preparation of estradiol, the efficient synthesis of the highly potent contraceptive desogestrel is discussed; for the synthesis of a-tocopherol and diversonol an enantioselective domino-Wacker/Heck reaction was utilized, whereas in the case of diversonol, a domino-Wacker/carbonylation was even more effective, and several molecular switches containing a helical tetrasubstituted double bond were prepared employing a domino-carbopalladation/Stille reaction. Finally, acenaphthylenes could be obtained by a domino-carbopalladation/C-H-activation.

DFT studies on oligocyclopropenones and related systems 5(n)-9(n) are reported. A strong sigma/pi interaction between the pi system and the or framework of the three-membered rings is observed in almost all cases, leading to a perpendicular arrangement of the pi systems in the most favored conformation. Also the shape of cyclic congeners is strongly influenced by sigma/pi interactions.

New photochromic switches based on helical alkenes can quickly and efficiently be accessed by Pd-catalyzed domino reactions using a modular approach; this allows a wide variability in product formation with the advantages of a convergent synthetic route. The alkenes have been synthesized in excellent enantioselectivity and their switching properties assessed by stimulation with nanosecond laser pulses at two different wavelengths in over 1000 switching cycles.

Helical tetrasubstituted alkenes (7) were obtained in a highly efficient way through a palladium-catalyzed domino-carbopalladation/CH-activation reaction of propargylic alcohols 6 in good to excellent yields. Electron-withdrawing- and electron-donating substituents can be introduced onto the upper and lower aromatic rings. The substrates (6) for the domino process were synthesized by addition of the lithiated alkyne (20) to various aldehydes (19); moreover, the substrates were accessible enantioselectively (in 95?% ee) by reduction of the corresponding ketone using the Noyori procedure.

A detailed theoretical study of dimethyldioxirane-mediated epoxidations with a variety of differently substituted alkenes 3-21 is presented. Transition structures and activation barriers were determined in the gas phase and in acetone as solvent with the B3LYP/6-311+G(d) level of theory. Substituent effects were elucidated by frontier orbital analyses of the reacting species as well as by natural bond orbital (NBO) analysis of the transition structures. Epoxidations with alkenes carrying electron-donating groups such as OMe or NHAc commonly tend to have low activation energies and early transitions states, whereas using alkenes with electron-withdrawing moieties such as CN, SO2Me, CO2Me, CF3, CHO, and Cl higher activation barriers and late transition states are observed. In all cases a net charge transfer (CT) from the alkene to the dioxirane was observed substantiating the electrophilic character of dimethyldioxirane.