Diastereoselective and enantioselective synthesis of tertiary alpha-hydroxy phosphonates through hydrogen-bond catalysis.
Diastereoselective and enantioselective synthesis of tertiary alpha-hydroxy phosphonates through hydrogen-bond catalysis.
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DOI：
10.1002/anie.200804244
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发表时间：
2009
影响因子：
16.6
通讯作者：
Rawal, Viresh H.
中科院分区：
文献类型：
--
作者：
Gondi, Vijaya Bhasker;Hagihara, Koji;Rawal, Viresh H.
羟醛缩合反应;布朗斯台德酸催化;对映选择性;氢键;膦酸酯α-官能化的膦酸衍生物具有生物医学意义，因为已经发现它们对几种重要的酶显示出抑制活性，所述酶包括肾素、凝血酶、ESPS合酶、HIV蛋白酶以及各种类型的蛋白酪氨酸激酶和磷酸酶。这些化合物的药用潜力刺激了其制备方法的发展，特别是对映体富集形式。大部分的努力都是针对α-羟基膦酸酯的合成，包括酶法[1，3，4]和化学方法[2，5-9]。现有的方法主要适用于合成仲α-羟基膦酸酯。一个值得注意的例外是Samantha和Zhao最近的报告，其中使用脯氨酸衍生物促进酮和酰基膦酸酯的羟醛缩合反应，生成叔α-羟基膦酸酯。[10]在这种和相关的羟醛缩合反应中，仲胺通过共价连接形成手性烯胺，其参与与羰基组分的非对映选择性加成反应。本文首次报道了氢键催化合成α-羟基膦酸叔酯的实例。在过去的十年中，氢键催化已迅速发展成为一种强有力的不对称合成策略。[11]在成功的应用中，这种模式在促进1，2-加成，大多数涉及使用亚胺作为亲电伙伴。[12]在氢键促进的羰基化合物的加成反应中，报道的例子主要涉及醛。[13我们推断酰氯等价物，例如酰基膦酸酯（或甚至酰基氰化物），可以在这样的反应中充当有效的亲电试剂，因为已知羟基膦酸酯产物是化学稳定的。β-取代的烯醇醚与乙酰基二甲基膦酸酯的反应将产生具有两个手性中心的产物，包括叔α-羟基膦酸酯，其通过补充不对称氢膦酰化反应的方法产生[方程式：①]。[8]后一种方法仅报道用于醛。
Keywords aldol reaction; brønsted acid catalysis; enantioselectivity; hydrogen bonds; phosphonates α-Functionalized phosphonic acid derivatives are of biomedical interest, as they have been found to display inhibitory activity towards several important groups of enzymes, including renin, thrombin, ESPS synthase, HIV protease, and various classes of protein tyrosine kinases and phosphatases. The pharmaceutical potential of these compounds has stimulated the development of methodology for their preparation, particularly in enantiomerically enriched forms. Much of this effort has been directed toward the synthesis of α-hydroxy phosphonates, including enzymatic [1, 3, 4] and chemical methods [2, 5–9]. The available methods are suitable primarily for the synthesis of secondary α-hydroxy phosphonates. A notable exception is the recent report of Samantha and Zhao, in which the use of proline derivatives to promote the aldol reaction of ketones and acylphosphonates yielded tertiary α-hydroxy phosphonates.[10] In this and related aldol reactions, the secondary amine, through covalent attachment, forms a chiral enamine that participates in a diastereoselective addition reaction with the carbonyl component. We report herein the first examples of tertiary α-hydroxy phosphonate ester synthesis promoted by hydrogen-bond catalysis. The reactions proceed in good yield and excellent diastereo-and enantioselectivity.Over the past decade hydrogen-bond catalysis has mushroomed into a powerful strategy for asymmetric synthesis.[11] Of the successful applications of this paradigm in the promotion of 1, 2-additions, most involve the use of an imine as the electrophilic partner.[12] Among hydrogen-bond-promoted additions to carbonyl compounds, the reported examples primarily involve aldehydes.[13, 14] We reasoned that acid chloride equivalents, such as acyl phosphonates (or perhaps even acyl cyanides), could function as effective electrophiles in such reactions because the hydroxy phosphonate product is known to be thermodynamically stable. The reaction of a β-substituted enol ether with acetyl dimethyl phosphonate would give a product having two chiral centers, including a tertiary α-hydroxy phosphonate, produced by a method that complements the asymmetric hydrophosphonylation reaction [Eq.(1)].[8] The latter process has only been reported for aldehydes.
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影响因子：
3.6
作者：
Cermak, DM;Du, YM;Wiemer, DF
通讯作者：
Wiemer, DF
影响因子：
--
作者：
Kafarski, P;Lejczak, B
通讯作者：
Lejczak, B
影响因子：
0.9
作者：
Nesterov, VV;Kolodyazhnyi, OI
通讯作者：
Kolodyazhnyi, OI
影响因子：
16.6
作者：
Hoashi, Y;Okino, T;Takemoto, Y
通讯作者：
Takemoto, Y
影响因子：
1.8
作者：
Kim, DY;Wiemer, DF
通讯作者：
Wiemer, DF