Apparent catalytic generation of chiral metal enolates:: Enantioselective dienolate additions to aldehydes mediated by Tol-BINAP•Cu(II) fluoride complexes
Apparent catalytic generation of chiral metal enolates:: Enantioselective dienolate additions to aldehydes mediated by Tol-BINAP•Cu(II) fluoride complexes
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DOI：
10.1021/ja973331t
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发表时间：
1998-02-04
影响因子：
15
通讯作者：
Carreira, EM
中科院分区：
文献类型：
--
作者：
Krüger, J;Carreira, EM
羰基加成反应的催化、对映选择性方法的发展是一个重要的研究热点。迄今为止报道的大多数方法涉及使用手性刘易斯酸，其活化醛组分以通过烯醇硅烷加成。1，2相反，递归生成参与对映选择性加成到醛的手性烯醇化物的催化过程的开发和研究几乎没有优先权。3-5在本文中，我们报告了一个过程，这似乎是通过催化生成的手性金属二烯醇化物引发的过渡金属氟化物络合物，很容易组装在原位混合（S）-Tol-BINAP，6 Cu（OTf）2，和（Bu 4 N）Ph 3SiF 2（TBAT）在THF中。的加合物被分离的范围内的醛在有用的产率和高达95%的对映体过量（ee），利用少至2摩尔%的催化剂。我们选择集中使用甲硅烷基二烯醇盐作为亲核试剂，因为分离的乙酰乙酸酯产物是通用的合成中间体，不仅允许获得δ-羟基β-酮酯，而且允许获得丙酮和乙酸酯衍生的羟醛加合物（方案1）。此外，可以通过该方法制备的羟基酮酯在HMG-CoA还原酶抑制剂和维生素D3类似物的持续开发中发挥了重要作用。8在催化对映选择性羟醛加成反应的最常用机制中，醛在与刘易斯酸配位后被活化，得到1（方案2）。亲电络合物被烯醇硅烷2攻击以产生中间体3，其必须以比甲硅烷基催化的羟醛加成反应的竞争背景速率更快的速率进行甲硅烷基化。9
The development of catalytic, enantioselective methods for carbonyl addition reactions is an important intense area of investigation. The majority of approaches reported to date involve the use of chiral Lewis acids that activate the aldehyde component toward addition by enol silanes. 1, 2 In contrast, the development and study of catalytic processes that recursively generate chiral enolates which participate in enantioselective addition to aldehydes has little precedence. 3-5 In this paper we report a process which appears to proceed by catalytic generation of a chiral metal dienolate initiated by a transition metal fluoride complex that is readily assembled in situ upon mixing (S)-Tol-BINAP, 6 Cu (OTf) 2, and (Bu4N) Ph3SiF2 (TBAT) in THF. The adducts are isolated for a range of aldehydes in useful yields and up to 95% enantiomeric excess (ee) utilizing as little as 2 mol% catalyst. We have chosen to focus on the use of the silyl dienolate as nucleophile since the acetoacetate products isolated are versatile synthetic intermediates allowing access not only to δ-hydroxy β-keto esters but also acetone and acetate derived aldol adducts (Scheme 1). 7 Moreover, the hydroxy keto esters that may be prepared through this process have played an important role in the ongoing development of HMG-CoA reductase inhibitors and Vitamin D3 analogues. 8In the most commonly exploited mechanism for catalytic enantioselective aldol addition reactions, an aldehyde is activated upon coordination to a Lewis acid to afford 1 (Scheme 2). The electrophilic complex is attacked by the enol silane 2 to produce intermediate 3 that must undergo silylation at a rate faster than the competing background rate of the silyl-catalyzed aldol addition reaction. 9