Rh-catalyzed highly enantioselective synthesis of 3-arylbutanoic acids.
Rh-catalyzed highly enantioselective synthesis of 3-arylbutanoic acids.
复制标题
DOI：
10.1002/anie.200604810
复制
发表时间：
2007-04
影响因子：
--
通讯作者：
Xianfeng Sun;Le Zhou;Chun‐Jiang Wang;Xumu Zhang
中科院分区：
文献类型：
--
作者：
Xianfeng Sun;Le Zhou;Chun‐Jiang Wang;Xumu Zhang
对映体纯的3-芳基丁酸及其衍生物如手性3-芳基丁醇是合成红没药烷家族的芳香族倍半萜的重要中间体[1]和有机合成中有用的结构单元。[2，3a]因此开发了各种羧酸的不对称合成，例如有机金属试剂对手性a，b-不饱和酯和酰胺的1，4-加成，[3]用许多亲核试剂和手性催化剂或促进剂的非对映异构体区分烷基化，[4]和手性仲苄醇的Mitsunobu反应。[5]然而，低的产率，中等的区域选择性，和狭窄的底物范围限制了这些反应的潜在应用。我们设想，最有效的方法之一，为建设这些部分将是不对称氢化相应的前立体3-芳基-3-丁烯酸。虽然在α芳基丙烯酸和其它α，b-不饱和酸与各种钌或铑配合物的不对称氢化方面已经取得了显著进展[6]，但由于中等的对映选择性（24 - 85%ee）和高催化剂负载量（1 - 2mol%），B，g-不饱和羧酸的不对称氢化仍然是一个主要挑战。[7]本文报道了一种铑催化的高对映选择性氢化制备手性3-芳基丁酸的方法，该方法具有以下特点：1）选择性高达99% ee，转化数（TONs）高达5000。2)高刚性的给电子P-手性双磷杂环戊烷配体与最佳溶剂和添加剂效应的组合是有效转化的关键。3)该方法简单易行，反应条件温和，具有高度的对映选择性，因此具有很强的实用性。通过Itoh等人开发的简单而通用的合成方法制备了一族前立体不饱和羧酸。[8]使用[Pd（PPh3）4]作为催化剂。[7b]正如Itoh的报告中所声称的，两个优点使得底物的制备特别适合于大规模合成。首先，反应可以通过双乙烯酮与芳基氯化锌试剂的钯（0）催化的偶联反应在一锅中完成，以高产率提供所需的3-芳基-3-丁烯酸。其次，通过重结晶或分馏可以容易地获得纯产品。[8，9]实现不对称氢化的高对映选择性和活性的关键点是找到有效的催化剂。[10]我们通过简单筛选几种手性磷配体开始了对3-苯基-3-丁烯酸的不对称氢化的研究（图1）。虽然配合物[Rh（S，S，R，R）-TangPhos（cod）] BF 4（3a; cod =
Enantiomerically pure 3-arylbutanoic acids and their derivatives such as chiral 3-arylbutanols are important intermediates for the synthesis of aromatic sesquiterpenes of the bisabolane family [1] and useful building blocks in organic synthesis.[2, 3a] A variety of asymmetric syntheses of the carboxylic acids have therefore been developed, such as 1, 4-addition of organometallic reagents to chiral a, b-unsaturated esters and amides,[3] diastereoface-differentiating alkylation with a number of nucleophiles and chiral catalysts or promoters,[4] and the Mitsunobu reaction of chiral secondary benzylic alcohols.[5] However, low yields, moderate regioselectivities, and narrow substrate scopes limit the potential applications of these reactions. We envision that one of the most effective methods for the construction of these moieties will be asymmetric hydrogenation of the corresponding prostereogenic 3-aryl-3-butenoic acids. Although significant progress has been made in asymmetric hydrogenation of aarylacrylic acids and other a, b-unsaturated acids with various ruthenium or rhodium complexes,[6] the asymmetric hydrogenation of b, g-unsaturated carboxylic acids still remains a major challenge owing to moderate enantioselectivities (24–85% ee) and high catalyst loadings (1–2 mol%).[7] Herein we report a Rh-catalyzed highly enantioselective hydrogenation for the preparation of chiral 3-arylbutanoic acids which has several outstanding features: 1) Selectivities of up to 99% ee and turnover numbers (TONs) of up to 5000 can be achieved. 2) The combination of a highly rigid electron-donating P-chiral bisphospholane ligand with optimal solvent and additive effects is the key to efficient transformations. 3) The simplicity of obtaining substrates and highly enantioselective hydrogenation under mild conditions make this approach very attractive and practical. A family of prostereogenic unsaturated carboxylic acids was prepared through a simple and versatile synthetic method developed by Itoh et al.[8] using [Pd (PPh3) 4] as a catalyst.[7b] As claimed in Itoh s report, two advantages make the preparation of substrates especially suitable for large-scale synthesis. First, reactions can be accomplished in one pot by a palladium (0)-catalyzed coupling reaction of diketene with an arylzinc chloride reagent, providing desired 3-aryl-3-butenoic acids in high yields. Second, pure products can be obtained easily by recrystallization or fractional distillation.[8, 9]A crucial point to achieving high enantioselectivities and activities for the asymmetric hydrogenation is finding effective catalysts.[10] We initiated our studies on the asymmetric hydrogenation of 3-phenyl-3-butenoic acid by briefly screening several chiral phosphorus ligands (Figure 1). Although the complexes [Rh (S, S, R, R)-TangPhos (cod)] BF4(3a; cod=