PubMed Health⌕ Search

Biomedical subjects

Thorsten Bach

Publications and source records attributed to Thorsten Bach.

26 records · Page 2Linked to original sources
PubMed2003

Complete control of regioselectivity in the intramolecular [2 + 2] photocycloaddition of 2-alkenyl-3(2H)-furanones by the length of the side chain.

The 2-(omega-alkenyl)-substituted 2-methyl-3(2H)-furanones 2a and 2b were prepared from biacetyl (3) in four reaction steps and in overall yields of 20% and 21%, respectively. They underwent a clean intramolecular [2 + 2] photocycloaddition upon irradiation at lambda = 350 nm. Whereas compound 2a reacted in the expected manner and yielded 7-oxabicyclo[3.2.1.0(3,6)]octane 7 (87% yield), the regioselectivity in the photocycloaddition of compound 2b was completely reversed. The reaction led to compound 8 (92% yield) with the unusual 9-oxabicyclo[4.2.1.0(3,8)]nonane skeleton, the structure of which was established by single-crystal X-ray crystallography.

Journal Article↗
PubMed2003

Enantioselective [6pi]-photocyclization reaction of an acrylanilide mediated by a chiral host. Interplay between enantioselective ring closure and enantioselective protonation.

The [6pi]-photocyclization of the anilides 1a and 5 was studied in the absence and in the presence of the enantiomerically pure chiral lactam 4. The relative configuration of the products was unambiguously established by single-crystal X-ray crystallography and by NMR spectroscopy. A significant enantiomeric excess was observed upon reaction of compound 1a to its photocyclization products at -55 degrees C employing lactam 4 as a chiral complexing agent in toluene as the solvent (66% yield). The trans product ent-3a was obtained in 57% ee, and the minor diastereoisomer (trans/cis = 73/27), cis product ent-2a, was obtained in 30% ee. DFT calculations were conducted modeling the complexation of intermediates 8 and ent-8 to host 4. In agreement with steric arguments concerning the conrotatory ring closure of 1a, the formation of ent-8 is favored leading to the more stable complex 4.ent-8 as compared to 4.8. Whereas the enantioselectivity in the photocyclization to trans compound ent-3a increased upon reduction in the reaction temperature, the enantiomeric excess in the formation of cis compound ent-2a went through a maximum at -15 degrees C (45% ee) and decreased at lower temperatures. Deuteration experiments conducted with the pentadeuterated analogue of 1a, d(5)-1a, revealed that the protonation of the intermediates 8 and ent-8 is influenced by chiral amide 4. In the formation of ent-3a/3a, both the enantioselective ring closure and the enantioselective protonation by amide 4 favor the observed (6aS,10aS)-configuration of the major enantiomer ent-3a. In the formation of ent-2a/2a, the enantioselective ring closure (and the subsequent diastereoselective protonation) favors the (6aR,10aS)-configuration that is found in compound 2a. Contrary to that, the enantioselective protonation by amide 4 shows a preference for ent-2a with the (6aS,10aR)-configuration.

Journal Article↗
PubMed2002

Synthesis of cystothiazole E and formal syntheses of cystothiazoles A and C by Pd0-catalyzed cross-coupling reactions.

The synthesis of the naturally occurring bithiazole (+)-cystothiazole E (1e) is described starting from oxazolidinone 2. It proceeded in 10 steps and an overall yield of 37%. The key reaction of the sequence was a Suzuki cross-coupling between bromobithiazole 4 and the (E)-alkenylboronic acid derived from alkyne 18 (94% yield). Prior to the synthesis, more general investigations related to the cross-coupling of bromobithiazole 4 were undertaken. Whereas Heck reactions failed Suzuki and Stille cross-coupling reactions were successfully conducted. By this means, the alkenylboronic acid derived from alkyne 11 and stannane 12 could be transformed into the corresponding alkenylbithiazoles 13 (92%) and 14 (52%). The Stille cross-coupling of compound 4 and stannane 5 allowed access to aldehyde 21 (97% yield) and paved the way for an alternative route to (+)-cystothiazole E (1e). In addition, aldehyde 21 was transformed into aldol product 22 (72%) which has been used in previous syntheses of cystothiazole A (1a) and C (1c). In this respect, the preparation of compound 21 represents a formal total synthesis of these cystothiazoles.

Journal Article↗
PubMed2002

Synthesis of 2'-substituted 4-bromo-2,4'-bithiazoles by regioselective cross-coupling reactions.

The synthesis of the title compounds (1) was achieved in two steps starting from readily available 2,4-dibromothiazole (2). In a regioselective Pd(0)-catalyzed cross-coupling step, compound 2 was converted into a variety of 2-substituted 4-bromothiazoles 3 (10 examples, 65-85% yield). Alkyl and aryl zinc halides were employed as nucleophiles to introduce an alkyl or aryl substituent. The Sonogashira protocol was followed to achieve an alkynyl-debromination. Bromo-lithium exchange at carbon atom C-4 and subsequent transmetalation to zinc or tin converted the 4-bromothiazoles 3 into carbon nucleophiles which underwent a second regioselective cross-coupling with another equivalent of 2,4-dibromothiazole (2). The Negishi cross-coupling gave high yields of the 2'-alkyl-4-bromo-2,4'-bithiazoles 1a-g (88-97%). The synthesis of the 2'-phenyl- and 2'-alkynyl-4-bromo-2,4'-bithiazoles 1h-j required a Stille cross-coupling that did not proceed as smoothly as the Negishi cross-coupling (58-62% yield). The title compounds which were accessible in total yields of 38-82% are versatile building blocks for the synthesis of 2,4'-bithiazoles.

Indicators and Reagents↗
PubMed2002

Highly enantioselective intra- and intermolecular [2 + 2] photocycloaddition reactions of 2-quinolones mediated by a chiral lactam host: host-guest interactions, product configuration, and the origin of the stereoselectivity in solution.

The [2 + 2] photocycloaddition of 4-alkoxy-2-quinolones was conducted in the presence of the chiral lactams 5 or ent-5. At -60 degrees C in toluene as the solvent the intramolecular reaction of quinolones 6 and 8 as well as the intermolecular photocycloaddition of various alkenes 13 to quinolone 12 proceeded with excellent enantioselectivity (81-98% ee) and in high yields (61-89%). Styrene (13d) reacted sluggishly in the intermolecular reaction (29% yield, 83% ee). The absolute configuration of the intramolecular photocycloaddition products 7 and 9 was elucidated by single-crystal X-ray crystallography of the corresponding diastereomeric N-menthyloxycarbonyl derivatives. The relative configuration of the intermolecular photocycloaddition products 14 and 15 was assigned on the basis of NOESY experiments and on crystallographic evidence. The differentiation of the enantiotopic faces in the prochiral quinolones 6, 8, and 12 can be explained by assuming a coordination of these substrates to the lactams 5 or ent-5 via two hydrogen bonds. Upon binding to 5 the si-face is shielded by the bulky tetrahydronaphthalene backbone, and the re-face is exposed to an intra- or intermolecular attack. On the basis of the association constant (K(a)) for the coordination of quinolone to host 5 an interpretation of the observed enantiomeric excess has been put forward. The parent quinolone 17 was employed as substrate for microcalorimetric and NMR titration experiments. From the data obtained for K(a) and DeltaH(a) the expected enantiomeric excess was calculated for two given temperatures (-15 and -60 degrees C). The calculated values fit the observed data within reasonable limits and prove that two-point hydrogen bonding can be sufficient to achieve a preparatively useful face differentiation in solution phase photochemistry.

Journal Article↗
PubMed2002

Enantioselective Norrish-Yang cyclization reactions of N-(omega-oxo-omega-phenylalkyl)-substituted imidazolidinones in solution and in the solid state.

The four N-(omega-oxo-omega-phenyl-alkyl)-substituted imidazolidinones 5-8 were prepared from N-acetylimidazolidinone (4). Upon irradiation, these substrates underwent Norrish-Yang cyclization to the racemic products rac-9-rac-12 (51-75%). The reactions of the N-2-oxoethylimidazolidinones 5 and 6 were conducted in tBuOH, and yielded 1:1 mixtures of exo/endo diastereoisomers rac-9a/rac-9b and rac-10a/rac-10b, accompanied by Norrish type II cleavage products. The reactions of the N-3-oxopropylimidazolidinones 7 and 8 were performed in toluene. The exo diastereoisomers rac-11a and rac-12a were the major diastereoisomers (d.r. approximately equal to 4:1). In the presence of the chiral compounds 1-3, the photocyclization of substrate 8 proceeded with significant enantiomeric excess (5-60% ee). The more sophisticated complexing agents 3 and ent-3 provided better enantiofacial differentiation (up to 60% ee) than the lactams 1 and 2 (up to 26% ee). Low temperatures and an excess of the complexing agent helped to increase the enantioselectivity. The absolute configuration of the major exo product 12a obtained from compound 8 in the presence of complexing agent 3 was unambiguously established by single-crystal X-ray crystallography of its chiral N-methoxyphenylacetyl derivative 15a. In a similar fashion, the absolute configurations of the endo products 12b and ent-12b were established. The N-2-oxoethylimidazolidinone 5, which crystallized in a chiral space group, was irradiated in the solid state. At low levels of conversion, the product 9a/ent-9a was formed with high enantiomeric excess (78% ee). The enantioselectivity deteriorated at higher levels of conversion.

Journal Article↗