Unveiling reliable catalysts for the asymmetric nitroaldol (Henry) reaction
Unveiling reliable catalysts for the asymmetric nitroaldol (Henry) reaction
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DOI：
10.1002/anie.200460506
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发表时间：
2004-01-01
影响因子：
16.6
通讯作者：
Mielgo, A
中科院分区：
文献类型：
--
作者：
Palomo, C;Oiarbide, M;Mielgo, A
硝基烷烃和羰基化合物之间的加成反应，即硝醛或亨利反应，早已为人所知。[1]它在有机化学中构成了一个强大的C？C键形成过程，[2]它提供了有效的途径来获得有价值的官能化结构基元，如1，2-氨基醇和α-羟基羧酸。[2，3]由于该反应是如此广为人知，可以想象，多年来可能已经投入了大量的努力来实现不对称版本的亨利反应。令人惊讶的是，直到最近几年才取得显著的成功。[4]亨利反应的立体控制仍然具有挑战性：控制正反立体化学是困难的，[5]使用共价键合的手性助剂作为一般策略还没有得到很大的发展，因为在亲核的硝基烷烃和醛成分中都缺乏合适的连接位置。[6，7]直到最近，随着新概念的应用到催化剂设计中，出现了可靠的催化系统，显著提高了亨利反应的当前合成价值。我们在此重点介绍这些发展背后的主要概念及其在该领域的影响。1973年Mukaiyama Aldol反应被发现后不久，手性金属促进剂和催化剂得到了稳定的开发，[8]但在1978年Seebach和Colvin[9]发现氟化物催化的硝酸硅酯和醛的反应之后，没有类似的进展。直到最近--大约25年后--两个独立的小组开发了手性催化剂。[10]Maruoka等人[10A]报道了在2mol%的手性季铵氟化盐4的存在下，三甲基硅基硝酸酯2与芳香醛1加成，得到了反：SYN比通常高于90：10和超过90%ee的3(方案1)。当涉及脂肪醛时，结果较差，但观察到的反选择性是基于手性硝酸铵作为活性物种的非环扩展过渡态模型来解释的。
The addition reaction between nitroalkanes and carbonyl compounds to yield a nitroalcohol, namely the nitroaldol or Henry reaction, has long been known.[1] It constitutes a powerful CÀC bond-forming process in organic chemistry,[2] providing efficient access to valuable functionalized structural motifs such as 1, 2-amino alcohols and α-hydroxy carboxylic acids.[2, 3] Because the reaction is so well known, it is conceivable that significant efforts may have been devoted over the years to implement asymmetric versions of the Henry reaction. Surprisingly no significant success has been achieved until the last few of years.[4] Stereocontrol in Henry reactions remains challenging: controlling the syn/anti stereochemistry is difficult,[5] and the use of covalently bonded chiral auxiliaries as a general strategy has not been much developed because of the lack of suitable attaching sites in both the pronucleophile nitroalkane and the aldehyde component.[6, 7] Only recently, with the application of new concepts to catalyst design, have reliable catalytic systems appeared that significantly increase the current synthetic value of the Henry reaction. We highlight here the main concepts behind these developments and their impact in the field.Relatively soon after the discovery of the Mukaiyama aldol reaction in 1973, chiral metal promoters and catalysts were steadily developed,[8] but no comparable progress followed the discovery by Seebach and Colvin [9] in 1978 of the fluoride-catalyzed reaction of silyl nitronates and aldehydes. Only quite recently—almost 25 years later—two independent groups have developed chiral catalysts.[10] Maruoka et al.[10a] have reported the addition of trimethylsilyl nitronates 2 to aromatic aldehydes 1 in the presence of 2 mol% of the chiral quaternary ammonium fluoride salt 4, to give 3 with anti: syn ratios usually higher than 90: 10 and with more than 90% ee (Scheme1). While poorer results are produced when aliphatic aldehydes are involved, the observed anti selectivity is explained on the basis of an acyclic extended transition-state model, which involves a chiral ammonium nitronate as the active species.