An acid inaccessible to aldol products The aldol reaction is a venerable and widely applicable method for making carbon-carbon bonds. Ironically, it is most challenged by the simplest substrates. The trouble is that the product looks a lot like one of the reactants, and so it can latch onto the coupling partner instead. Schreyer et al. report that a bulky phosphorus-based acid catalyst alleviates this problem. The acidic site is buried in a pocket that is too small to activate the product for further reaction. The chiral geometry of the catalyst also induces high enantioselectivity. Science, this issue p. 216 A phosphorus-based acid catalyst envelops its substrate to form just one carbon-carbon bond selectively. Reactions that form a product with the same reactive functionality as that of one of the starting compounds frequently end in oligomerization. As a salient example, selective aldol coupling of the smallest, though arguably most useful, enolizable aldehyde, acetaldehyde, with just one partner substrate has proven to be extremely challenging. Here, we report a highly enantioselective Mukaiyama aldol reaction with the simple triethylsilyl (TES) and tert-butyldimethylsilyl (TBS) enolates of acetaldehyde and various aliphatic and aromatic acceptor aldehydes. The reaction is catalyzed by recently developed, strongly acidic imidodiphosphorimidates (IDPi), which, like enzymes, display a confined active site but, like small-molecule catalysts, have a broad substrate scope. The process is scalable, fast, efficient (0.5 to 1.5 mole % catalyst loading), and greatly simplifies access to highly valuable silylated acetaldehyde aldols.

中文翻译：

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受限酸催化乙醛烯醇化物的不对称单醛醇化

醛醇产物无法获得的酸 醛醇反应是一种古老且广泛适用的制备碳-碳键的方法。具有讽刺意味的是，它受到最简单的基材的最大挑战。麻烦的是，该产品看起来很像一种反应物，因此它可以锁定在偶联伙伴上。施莱尔等人。据报道，体积大的磷基酸催化剂缓解了这个问题。酸性位点被埋在一个太小而无法激活产品以进行进一步反应的口袋中。催化剂的手性几何形状也诱导了高对映选择性。科学，这个问题 p。216 一种磷基酸催化剂包裹其底物，选择性地仅形成一个碳-碳键。形成具有与起始化合物之一相同的反应性官能团的产物的反应通常以低聚反应结束。作为一个突出的例子，最小的，虽然可以说是最有用的，可烯醇化的醛，乙醛，与只有一个伙伴底物的选择性羟醛偶联已被证明是极具挑战性的。在这里，我们报告了与乙醛和各种脂肪族和芳香族受体醛的简单三乙基甲硅烷基 (TES) 和叔丁基二甲基甲硅烷基 (TBS) 烯醇化物的高度对映选择性 Mukaiyama 羟醛反应。该反应由最近开发的强酸性亚氨基二磷酰亚胺 (IDPi) 催化，IDPi 与酶一样，显示出受限的活性位点，但与小分子催化剂一样，具有广泛的底物范围。该过程可扩展、快速、高效（0.5 至 1.5 摩尔% 催化剂负载），