TY - JOUR
T1 - Enantioselective [6π]-photocyclization reaction of an acrylanilide mediated by a chiral host. Interplay between enantioselective ring closure and enantioselective protonation
AU - Bach, Thorsten
AU - Grosch, Benjamin
AU - Strassner, Thomas
AU - Herdtweck, Eberhardt
PY - 2003/2/7
Y1 - 2003/2/7
N2 - The [6π]-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 °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 la, 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 °C (45% ee) and decreased at lower temperatures. Deuteration experiments conducted with the pentadeuterated analogue of 1a, d5-1a, 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.
AB - The [6π]-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 °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 la, 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 °C (45% ee) and decreased at lower temperatures. Deuteration experiments conducted with the pentadeuterated analogue of 1a, d5-1a, 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.
UR - http://www.scopus.com/inward/record.url?scp=0037423365&partnerID=8YFLogxK
U2 - 10.1021/jo026602d
DO - 10.1021/jo026602d
M3 - Article
AN - SCOPUS:0037423365
SN - 0022-3263
VL - 68
SP - 1107
EP - 1116
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 3
ER -