Asymmetric synthesis of chiral aldehydes by conjugate additions with bifunctional organocatalysis by cinchona alkaloids
Asymmetric synthesis of chiral aldehydes by conjugate additions with bifunctional organocatalysis by cinchona alkaloids
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DOI：
10.1002/anie.200600867
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Deng, Li
中科院分区：
文献类型：
--
作者：
Wu, Fanghui;Hong, Ran;Deng, Li
醛可以说是最通用的羰基官能团。此外，它比任何其他羰基官能团对过多的亲核反应更有活性。这种功能多样性和活性的独特组合使得手性醛在不对称合成中具有高度价值的中间体。大量涉及醛作为亲核试剂或亲电试剂的催化对映选择性反应的出现进一步提高了手性醛的合成价值。手性醛的对映选择性转化是制备光学活性醛的重要途径。特别是，在手性烯胺催化下与前手性醛的α-碳原子形成对映选择性键，[1，2]手性亚铵催化下的对映选择性环加成和Friedel-Crafts反应[3]以及芳基硼酸和甲硅烷基硝基膦酸酯与α，分别用手性过渡金属催化剂[4]和手性相转移催化剂[5]合成β-不饱和醛。尽管其在合成中的重要性，但羰基供体与α，β-不饱和醛的高度对映选择性和一般共轭加成仍然难以捉摸，即使付出了相当大的努力。[6-8]在此，我们希望报告的重大进展，这种反应的发展与金鸡纳生物碱衍生的有机催化剂。在我们的研究开始时，我们担心3a的分解可以由金鸡纳生物碱作为亲核催化剂（方案1）触发，这是根据1，4-二氮杂双环-[2.2. 2]辛烷（DABCO）和奎宁环在Morita-Baylis-Hillman（MBH）反应中。[9]事实上，发现3a在DABCO、奎宁环或β异铜环的存在下快速分解形成不溶性低聚物或聚合物。另一方面，我们的机制研究表明，金鸡纳生物碱，如二氢奎尼丁，
The aldehyde is arguably the most versatile carbonyl functionality. Furthermore, it is more active than any other carbonyl functionality toward a plethora of nucleophilic reactions. This unique combination of functional versatility and activity renders chiral aldehydes highly valuable intermediates in asymmetric synthesis. The emergence of numerous catalytic enantioselective reactions that involve aldehydes as either nucleophiles or electrophiles further enhances the synthetic value of chiral aldehydes. Enantioselective transformations of the readily available prochiral aldehydes are now emerging as a fundamentally important approach toward optically active aldehydes. In particular, great strides have been made in the development of enantioselective bond formations with the α-carbon atom of prochiral aldehydes with chiral enamine catalysis,[1, 2] enantioselective cycloadditions and Friedel–Crafts reactions with chiral immonium catalysis,[3] and conjugate additions of aryl boronic acids and silyl nitronates to α, β-unsaturated aldehydes by chiral transition-metal catalysis [4] and chiral phase-transfer catalysts,[5] respectively. Despite its synthetic importance, the highly enantioselective and general conjugate addition of carbonyl donors to α, β-unsaturated aldehydes remains elusive, even with considerable efforts.[6–8] Herein, we wish to report significant progress toward the development of such a reaction with cinchona-alkaloid-derived organic catalysts. At the outset of our investigations, we were concerned that the decomposition of 3a could be triggered by cinchona alkaloids as nucleophilic catalysts (Scheme 1) in light of the well-documented nucleophilic catalysis of 1, 4-diazabicyclo-[2.2. 2] octane (DABCO) and quinuclidine in the Morita–Baylis–Hillman (MBH) reaction.[9] Indeed, 3a was found to rapidly undergo decomposition to form insoluble oligomers or polymers in the presence of DABCO, quinuclidine, or βisocupreidine. On the other hand, mechanistic studies by us established that cinchona alkaloids, such as dihydroquinidine