Desimoni Giovanni, Faita Giuseppe, Toscanini Marco, Boiocchi Massimo
Dipartimento di Chimica Organica dell'Università di Pavia, Viale Taramelli 10, 27100 Pavia, Italy.
Chemistry. 2007;13(34):9478-85. doi: 10.1002/chem.200700995.
The cycloaddition between methyl (E)-2-oxo-4-aryl-3-butenoates (2 a-d) and cyclopentadiene, in addition to the expected normal Diels-Alder (DA) adducts endo-3 a-d and exo-4 a-d, gives the less expected endo-5 a-d products of the [4+2] hetero-Diels-Alder (HDA) reaction in which the alpha-ketoester behaves as a heterodiene. If a comparison is made between the thermal and the scandium(III) triflate-catalyzed conditions, the periselectivity changes and whereas under thermal conditions the main products are those from the DA reaction (3 a-d), in the presence of Sc(OTf)3 (OTf=triflate), the HDA products 5 a-d become largely predominant. The reactions are enantioselectively catalyzed by the scandium(III) triflate complex of (4'S,5'S)-2,6-bis[4'-(triisopropylsilyl)oxymethyl-5'-phenyl-1',3'-oxazolin-2'-yl]pyridine (1) and both the DA and the HDA products are obtained with excellent enantiomeric excess, up to >99% ee. The X-ray crystallographic structure determination of 5 c assigns it the 4R,4aS,7aR absolute configuration. The thermal retro-Claisen rearrangement of 3 c into (4R,4aS,7aR)-5 c allows the correlation of their absolute configuration, and 3 c has therefore the 2R,3R configuration. By analogy the same absolute configuration can be assigned to 3 a,b,d and 5 a,b,d, and the stereospecific thermal Claisen rearrangement of the optically active 5 a,b,d into 3 a,b,d completes the correlation between their absolute configuration. The [3,3]-sigmatropic rearrangements can be easily carried out under catalytic conditions with scandium(III) triflate, which promotes the equilibration between 3 a-d and 5 a-d, with a different degree of enantioselectivity characterizing the process starting from 3 a-d or 5 a-d. The unambiguous attributions of the configuration to the products allows us to propose a rationale of the stereochemical outcome of the catalyzed cycloaddition and to investigate the reaction mechanism of the competing DA and HDA reactions and shifts in products distribution by acid catalysis.
（E）-2-氧代-4-芳基-3-丁烯酸甲酯（2 a-d）与环戊二烯之间的环加成反应，除了生成预期的正常狄尔斯-阿尔德（DA）加合物内型-3 a-d和外型-4 a-d外，还生成了较意外的[4+2]杂狄尔斯-阿尔德（HDA）反应的内型-5 a-d产物，其中α-酮酯表现为杂二烯。如果比较热反应条件和三氟甲磺酸钪催化的条件，周环选择性会发生变化，在热反应条件下主要产物是来自DA反应的产物（3 a-d），而在三氟甲磺酸钪（OTf = 三氟甲磺酸盐）存在下，HDA产物5 a-d成为主要产物。反应由（4'S,5'S）-2,6-双[4'-（三异丙基甲硅烷基）氧甲基-5'-苯基-1',3'-恶唑啉-2'-基]吡啶（1）的三氟甲磺酸钪配合物进行对映选择性催化，DA产物和HDA产物均以优异的对映体过量得到，高达>99% ee。5 c的X射线晶体结构测定确定其绝对构型为4R,4aS,7aR。3 c热重排为（4R,4aS,7aR）-5 c使得它们的绝对构型能够关联起来，因此3 c具有2R,3R构型。以此类推，相同的绝对构型可赋予3 a、b、d和5 a、b、d，光学活性的5 a、b、d立体定向热克莱森重排为3 a、b、d完成了它们绝对构型之间的关联。[3,3]-σ迁移重排可以在三氟甲磺酸钪催化条件下轻松进行，这促进了3 a-d和5 a-d之间的平衡，从3 a-d或5 a-d开始的过程具有不同程度的对映选择性。对产物构型的明确归属使我们能够提出催化环加成反应立体化学结果的原理，并研究竞争的DA反应和HDA反应的反应机理以及酸催化下产物分布的变化。
