Asymmetric Diels-Alder reactions of α,β-unsaturated aldehydes catalyzed by a diarylprolinol silyl ether salt in the presence of water
Asymmetric Diels-Alder reactions of α,β-unsaturated aldehydes catalyzed by a diarylprolinol silyl ether salt in the presence of water
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DOI：
10.1002/anie.200801408
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Ishikawa, Hayato
中科院分区：
文献类型：
--
作者：
Hayashi, Yujiro;Samanta, Sampak;Ishikawa, Hayato
Diels-Alder反应是构建区域和立体化学定义的环己烷骨架的一种有效的合成方法。有几种催化对映体选择性的方法，[1]MacMillan和他的同事开发了第一个涉及有机催化剂的Diels-Alder反应，它通过降低LUMO的活化机理进行。[2]此后，几个涉及有机催化剂的不对称Diels-Alder反应被报道。[3，4]我们的小组[5]和Jórgensen的[6]在2005年开发了一种二芳基脯氨醇硅基醚作为有效的有机催化剂，这种类型的催化剂被广泛应用于几个不对称反应中。[7]最近，我们发现二芳基丙基硅醚1与CF3CO2H结合是甲苯中有效的Diels-Alder催化剂。水作为反应介质因其独特的性质在现代有机化学中引起了极大的兴趣。[9]例如，在Diels-Alder反应中，反应在“水中”(均相稀释条件)[10]和“在水中”(两相条件)[10]加速。[11]我们报道了水对不对称Aldol反应的非对映选择性和对映选择性的影响。[12]Palomo等[13]和Ma及其同事[14]报道了在水存在下，二烷基和二苯丙基硅醚分别催化的不对称Michael反应。已知一些有机催化反应受溶解水的影响，[15]基于我们对在水存在下的反应的兴趣，[16]我们使用二芳基脯氨醇硅基醚作为有机催化剂考察了不对称Diels-Alder反应。虽然Norhorup和MacMillan[2b]和Ogilvie及其同事[3c，g，h]报道了水存在下的不对称Diels-Alder反应，但我们开发了一种绿色实用的方法，即使在纯化步骤中也不需要有机溶剂。我们还观察到了一个有趣的现象，即水对反应的速率和对映体选择性的积极影响，这不同于“对水”反应，将在这里描述。首先，我们选择了肉桂醛和环戊二烯之间的模型反应，我们发现在甲苯中1(图1)和CF3CO2H的组合在20小时内促进了该反应(表1，条目1)。[8]当我们使用水作为溶剂时，形成了两相体系，反应进行缓慢，提供了较低的产率和中等的对映选择性(表1，条目2)。发现酸对反应的产率有重要影响(表1)。在弱酸如CCl3CO2H的存在下反应较慢(表1，条目3)，而在氟化的存在下对映体选择性增加
The Diels–Alder reaction is a powerful synthetic method for the construction of regio-and stereochemically defined cyclohexane frameworks. There are several catalytic enantioselective methods,[1] and MacMillan and co-workers developed the first Diels–Alder reaction involving an organocatalyst, which proceeds by a LUMO-lowering activation mechanism.[2] Since then several asymmetric Diels–Alder reactions involving organocatalysts have been reported.[3, 4] Our group [5] and that of Jørgensen [6] developed a diarylprolinol silyl ether as an effective organocatalyst in 2005, and this type of catalyst has since been employed widely in several asymmetric reactions.[7] Recently, we found that diarylprolinol silyl ether 1 combined with CF3CO2H is an effective Diels–Alder catalyst in toluene.[8] In contrast, water has attracted a lot of interest as a reaction medium in current organic chemistry because of its unique properties.[9] In the Diels–Alder reaction, for instance, the reaction is accelerated “in water”(homogeneous dilute conditions)[10] and “on water”(biphasic conditions).[11] We reported the positive effect of water on diastereo-and enantioselectivities for the asymmetric aldol reaction in the presence of water.[12] Palomo et al.[13] and Ma and co-workers [14] reported the enantioselective Michael reaction catalyzed by dialkyl-and diphenylprolinol silyl ethers, respectively in the presence of water. Some organocatalyzed reactions are known to be affected by dissolved water,[15] and on the basis of our interest in reactions in the presence of water,[16] we have examined the enantioselective Diels–Alder reaction by using diarylprolinol silyl ether as an organocatalyst. Although Northrup and MacMillan [2b] and Ogilvie and co-workers [3c, g, h] reported the asymmetric Diels–Alder reaction in the presence of water, we developed a green and practical procedure that does not require an organic solvent, even for the purification step. We also observed an interesting phenomenon, namely the positive effect of water on the rate and enantioselectivity of the reaction, which is different from that of the “on water” reaction and will be described herein. First, we chose the model reaction between cinnamaldehyde and cyclopentadiene, which we had found to be promoted by a combination of 1 (Figure 1) and CF3CO2H in toluene within 20 hours (Table 1, entry 1).[8] When we used water as a solvent, a biphasic system formed and the reaction proceeded slowly, affording the product in lower yield with moderate enantioselectivity (Table1, entry2). Acid was found to have an important effect on the yield of the reaction (Table 1). The reaction was slower in the presence of a weaker acid such as CCl3CO2H (Table1, entry3), whereas the enantioselectivity increased in the presence of fluorinated