Bach Thorsten, Grosch Benjamin, Strassner Thomas, Herdtweck Eberhardt
Lehrstuhl für Organische Chemie I, Technische Universität München, D-85747 Garching, Germany.
J Org Chem. 2003 Feb 7;68(3):1107-16. doi: 10.1021/jo026602d.
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.
在无对映体纯的手性内酰胺4存在和存在的情况下，研究了苯胺1a和5的[6π]光环化反应。通过单晶X射线晶体学和核磁共振光谱明确确定了产物的相对构型。在-55℃下，以内酰胺4作为手性络合剂，甲苯作为溶剂，化合物1a与其光环化产物反应时观察到显著的对映体过量（产率66%）。反式产物ent-3a的对映体过量为57%，次要非对映异构体（反式/顺式=73/27），顺式产物ent-2a的对映体过量为30%。进行了密度泛函理论计算，模拟中间体8和对映体ent-8与主体4的络合。与关于1a的对旋环化的空间论点一致，与4·8相比，ent-8的形成更有利，导致形成更稳定的络合物4·ent-8。虽然光环化生成反式化合物ent-3a时的对映选择性随着反应温度的降低而增加，但顺式化合物ent-2a形成时的对映体过量在-15℃达到最大值（45%ee），并在更低温度下降低。用1a的五氘代类似物d(5)-1a进行的氘代实验表明，中间体8和对映体ent-8的质子化受手性酰胺4的影响。在ent-3a/3a的形成中，对映选择性环化和酰胺4的对映选择性质子化都有利于主要对映体ent-3a所观察到的(6aS,10aS)构型。在ent-2a/2a的形成中，对映选择性环化（以及随后的非对映选择性质子化）有利于化合物2a中发现的(6aR,10aS)构型。与此相反，酰胺4的对映选择性质子化显示出对具有(6aS,10aR)构型的ent-2a的偏好。
