Catalytic enantioselective Hosomi-Sakurai conjugate allylation of cyclic unsaturated ketoesters
Catalytic enantioselective Hosomi-Sakurai conjugate allylation of cyclic unsaturated ketoesters
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DOI：
10.1002/anie.200800628
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Snapper, Marc L.
中科院分区：
文献类型：
--
作者：
Shizuka, Manami;Snapper, Marc L.
尽管多年来取得了令人印象深刻的进步，[1] 仍然存在缺乏催化不对称变体的重要转化。虽然路易斯酸催化烯丙基硅烷与羰基化合物 [2] 和缩醛 [3] 的加成已经使用催化 [4] 以及基于辅助的方法来控制绝对构型进行了深入研究，[5] 据我们所知，尚无有效的方法来催化烯丙基三甲基硅烷与不饱和羰基化合物的不对称 1, 4-加成。 [6]在这方面，我们在此报道了烯丙基三甲基硅烷与各种活化环烯酮的催化对映选择性共轭加成，选择性超过 98% ee。在 Cu (OTf) 2 (10 mol%) 存在下，使用市售的二(叔丁基)双(恶唑啉)(盒)配体 (2)，将空气和湿气稳定的亲核试剂与不饱和羰基化合物进行 1, 4-加成，转化率> 95%。 [7]我们展示了如何将这些产品功能化为各种有用的对映体富集系统。我们对手性路易斯酸催化剂开发的初步研究表明，简单的环状和无环 α, β 不饱和羰基（酮和酯）不会与各种金属-配体组合发生反应。 [8]因此，我们试图通过在烯酮的α位（即1）安装第二个吸电子/螯合基团来激活底物。在 Cl (CH2) 2Cl 中存在 Cu (OTf) 2 (7 mol%) 和双 (恶唑啉) 配体 2 (8 mol%) 的情况下，我们获得了所需的 1, 4-烯丙基加成产物 3，转化率 > 95%（08℃ 30 分钟后）和 72% ee，为酮-烯醇互变异构体的混合物（方案 1）。替代溶剂（CH2Cl2、Et2O、甲苯、EtOAc 等）和金属盐（包括其他铜盐）导致选择性较低。 [9]其他手性配体（例如，基于肽的[10] salen、[11] Trost 配体[12]）可实现高转化率（> 95%），但选择性较低（< 5% ee）。为了确定更有效的催化剂，我们制备并筛选了大约 40 种单和双（恶唑啉）配体。所研究的双（恶唑啉）配体的选择如表 1 所示。苯甘氨酸和苯丙氨酸衍生的配体（分别为 7 和 8）转化率较高，但转化率较低
Despite impressive advances over the years,[1] there are still important transformations that lack catalytic asymmetric variants. While Lewis acid catalyzed additions of allylsilanes to carbonyl compounds [2] and acetals [3] have been well studied using catalytic,[4] as well as auxiliary-based methods to control absolute configuration,[5] to the best of our knowledge, there are no effective methods for catalyzing the asymmetric 1, 4-addition of allyltrimethylsilane to unsaturated carbonyl compounds.[6] In that regard, we report herein a catalytic enantioselective conjugate addition of allyltrimethylsilane to various activated cyclic enones with selectivities surpassing 98% ee. The 1, 4-addition of the air-and moisture-stable nucleophile to unsaturated carbonyl compounds proceeds to> 95% conversion in the presence of Cu (OTf) 2 (10 mol%) with the commercially available di (tert-butyl) bis (oxazoline)(box) ligand (2).[7] We show how these products can be functionalized to a variety of useful enantiomerically enriched systems.Our initial studies into the development of a chiral Lewis acid catalyst indicated that simple cyclic and acyclic α, βunsaturated carbonyls (ketones and esters) did not react with a variety of metal–ligand combinations.[8] We therefore sought to activate the substrate by installation of a second electron-withdrawing/chelating group at the α-position of the enone (ie, 1). In the presence of Cu (OTf) 2 (7 mol%) and bis (oxazoline) ligand 2 (8 mol%) in Cl (CH2) 2Cl, we obtained the desired 1, 4-allyl-addition product 3 in> 95% conversion (after 30 min at 08C) and 72% ee as a mixture of keto–enol tautomers (Scheme 1). Alternative solvents (CH2Cl2, Et2O, toluene, EtOAc, etc.) and metal salts, including other copper salts, resulted in lower selectivities.[9] Other chiral ligands (eg, peptide-based,[10] salen,[11] Trost ligand [12]) led to high conversion (> 95%), but with low selectivity (< 5% ee). To identify a more effective catalyst, we prepared and screened approximately 40 mono-and bis (oxazoline) ligands. A selection of the bis (oxazoline) ligands studied are illustrated in Table 1. Phenylglycine-and phenylalanine-derived ligands (7 and 8, respectively) gave high conversions, but low