Rhodium-catalyzed enantioselective reductive aldol reaction
Rhodium-catalyzed enantioselective reductive aldol reaction
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DOI：
10.1021/ja9944453
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发表时间：
2000-05-10
影响因子：
15
通讯作者：
Morken, JP
中科院分区：
文献类型：
--
作者：
Taylor, SJ;Duffey, MO;Morken, JP
催化的对映选择性碳-碳偶联反应，特别是那些从容易获得的前手性底物形成C（sp3）-C（sp3）键的反应，是合成天然产物和商品化学品的有用工具。这种成键模式可用于通过催化不对称Aldol反应合成β-羟基羰基化合物。1，2除了纳尔逊、3柴崎、4和渡边的报道外，5用于催化不对称合成β-含氧羰基化合物的方法从潜在的烯醇化物衍生反应性，所述烯醇化物必须以化学计量的方式预先制备。[6]我们最近报道了一种非对映选择性催化还原羟醛缩合反应，该反应可能为这种向山羟醛缩合过程提供一种替代方法。7-9还原性羟醛缩合反应不需要预先形成金属烯醇化物或甲硅烷基烯醇醚;活化的烯烃、醛和硅烷之间的催化缩合直接使受保护的丙酸酯产物脱保护。开发有效的还原性羟醛催化剂的挑战包括反应立体选择性和产物选择性;醛和硅烷之间的后过渡金属催化缩合（羰基氢化硅烷化10）和丙烯酸酯和硅烷之间的后过渡金属催化缩合（烯烃氢化硅烷化11）是众所周知的过程，并且是潜在的竞争反应途径。本文报道了第一个不对称催化还原Aldol反应，由[（cod）RhCl] 2和2，2′-二（二苯基膦基）-1，1 ′-联萘（BINAP）12衍生的配合物催化丙烯酸酯和醛之间的非对映选择性和对映选择性还原Aldol反应，具有良好的对映选择性. 13我们对192个独立的催化剂体系的初步研究将[（cod）RhCl] 2-R-BINAP-Et 2 MeSiH鉴定为能够实现丙烯酸甲酯和苯甲醛之间的室温催化对映选择性还原羟醛缩合反应的一种催化剂体系。虽然在初始微量测定中的对映体选择性低（20%对映体过量），但注意到在配体存在下的反应比仅用金属盐的反应效率低（4%相对产率对16%相对产率，数据未显示）。我们推测，在微型反应期间，配体与金属的低效络合可能会留下未络合的金属盐，以实现相对快速和非选择性的转化。在存在过量R-BINAP的情况下放大后（1.3：1配体/金属; 2.5mol%[（cod）RhCl] 2）丙烯酸甲酯、苯甲醛和二乙基甲基硅烷之间发生催化还原性羟醛缩合反应，得到非对映体混合物（1.7：1顺式：反式）以良好的对映体过量（91%ee顺式; 88%ee反式，37%产率;参见表1，条目1）制备β-羟基酯。值得注意的是，非对映选择性的丧失是由于在与前手性羰基的键形成中缺乏立体控制而发生的;在CR处的立体选择性的意义和水平保持良好的保真度。在干燥和无氧的氮气气氛下，将2.5摩尔%[（cod）-RhCl] 2与6.5摩尔% R-BINAP在二氯乙烷中在室温下搅拌1小时。然后加入二乙基甲基硅烷，并将混合物再搅拌30分钟。
Catalytic enantioselective carbon-carbon coupling reactions, particularly those that form C (sp3)-C (sp3) bonds from readily available prochiral substrates, are useful tools for the synthesis of natural products and commodity chemicals. Such a mode of bond formation is available for the asymmetric synthesis of β-hydroxy carbonyls through catalytic enantioselective aldol processes. 1, 2 With the exception of reports by Nelson, 3 Shibasaki, 4 and Watanabe, 5 methods for the catalytic asymmetric synthesis of β-oxygenated carbonyls derive reactivity from latent enolates which must be prepared, in advance, in a stoichiometric fashion. 6 We recently reported a diastereoselective catalytic reductive aldol reaction that may provide an alternative to such Mukaiyama aldol processes. 7-9 The reductive aldol reaction does not require preformation of metal enolates or silyl enol ethers; catalytic condensation between an activated alkene, an aldehyde, and a silane directly furnishes protected propionate products. Challenges to the development of effective reductive aldol catalysts include reaction stereoselection and also product selectivity; late transition metal-catalyzed condensations between aldehydes and silanes (carbonyl hydrosilation10) and between acrylates and silanes (alkene hydrosilation11) are well-known processes and are potential competing reaction pathways. Herein we report the first asymmetric catalytic reductive aldol reaction; a complex derived from [(cod) RhCl] 2 and 2, 2′-bis (diphenylphosphino)-1, 1′-binaphthyl (BINAP) 12 effects catalytic diastereoselective and enantioselective reductive aldol reaction between acrylate esters and aldehydes with good to excellent levels of enantioselectivity. 13 Our initial studies with 192 independent catalyst systems identified [(cod) RhCl] 2-R-BINAP-Et2MeSiH as one catalyst system able to effect room-temperature catalytic enantioselective reductive aldol reaction between methyl acrylate and benzaldehyde. While enantioselectivity in the initial microscale assay was low (20% enantiomeric excess), it was noted that reaction in the presence of ligand was less efficient than the reaction with metal salt alone (4% relative yield versus 16% relative yield, data not shown). We surmised that during the microscale reaction, inefficient complexation of the ligand to the metal might leave uncomplexed metal salt available to effect relatively rapid and nonselective transformation. Upon scale-up in the presence of excess R-BINAP (1.3: 1 ligand/metal; 2.5 mol%[(cod) RhCl] 2) the catalytic reductive aldol reaction between methyl acrylate, benzaldehyde, and diethylmethylsilane occurs to provide a diastereomeric mixture (1.7: 1 syn: anti) of β-hydroxy esters in good enantiomeric excess (91% ee syn; 88% ee anti, 37% yield; see Table 1, entry 1). 14 Notably, loss of diastereoselection occurs from lack of stereocontrol in bond formation to the prochiral carbonyl; the sense and level of stereoselection at CR is maintained with good fidelity.The impact of acrylate and aldehyde structure on stereoselection was examined with the following experimental procedure: Under a dry and oxygen-free nitrogen atmosphere, 2.5 mol%[(cod)-RhCl] 2 was stirred with 6.5 mol% R-BINAP in dichloroethane at room temperature for 1 h. Diethylmethylsilane was then added and the mixture stirred for an additional 30 min. After addition of carbonyl substrates, the reaction was allowed to proceed for