A chiral Lewis acid strategy for enantioselective allylic C-H oxidation
A chiral Lewis acid strategy for enantioselective allylic C-H oxidation
复制标题
DOI：
10.1002/anie.200802106
复制
发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
White, M. Christina
中科院分区：
文献类型：
--
作者：
Covell, Dustin J.;White, M. Christina
C2 H4氧化反应具有显著简化合成过程的潜力。然而，为了用于合成复杂分子，这些反应必须以高水平的化学选择性、区域选择性和立体选择性进行。手性双恶唑啉/铜催化体系在对称环烯烃的不对称烯丙基C2 H4酯化反应中表现出很好的不对称诱导作用。这些系统对复杂底物的应用受到缺乏化学和区域选择性以及需要使用大量过量反应物（4至10当量）的限制。[1]一个直接烯丙基C2 H4氧化路线将显着提高生产手性烯丙基酯的效率，它们的合成通常需要冗长的序列的功能基团的操作从预氧化的材料。[2，3]我们最近报道了α-烯烃的温和的、高度区域选择性和化学选择性的烯丙基C2 H4酯化[4]和胺化[5]反应，并证明了它们在简化复杂分子合成中的实用性。[6]这些烯丙基氧化反应催化的Pd II系统与弱配位的亚砜和醌配体，不适合影响不对称诱导。[7]本文中，我们公开了一种新的手性刘易斯酸策略，用于在亲电氧化反应中产生关于金属中心的不对称环境，所述亲电氧化反应不耐受强配位配体。在我们的方法中，使用的手性刘易斯酸选择性地与有机钯中间体相互作用，以加速和诱导的不对称性的C13 O键形成步骤。值得注意的是，通过使用这种策略，我们已经实现了迄今为止观察到的末端烯烃的烯丙基C2 H4氧化的最高对映体选择性（方案1）。[8]该系统代表了手性刘易斯酸影响的有机金属中间体的不对称诱导的第一个例子，以及钯催化的对映选择性C3 H4活化的罕见例子。[9]不对称有机金属反应的传统方法使用强配位手性配体。1氧化末端烯烃生成支链烯丙基化合物是通过一系列配体催化机理进行的，其中弱配位的双亚砜和1，4-苯醌（BQ）配体依次与Pd中心相互作用，分别促进C1 H2-H键断裂和C1 H2-O键形成步骤.（方案1）。[4b]理论上，任一配体的手性变体可导致对映体富集的产物。使用手性亚砜的所有尝试在实现不对称诱导方面都是不成功的。使用顺式-[1-D]-1-癸烯的实验表明，这种无效性是由于[（π-烯丙基）Pd]中间体的快速π-σ-π异构化，其扰乱了在C2 H4裂解步骤期间赋予的任何手性信息（方案1，参见支持信息）。因此，我们着手确定一个可行的替代战略，对映选择性的C2 H2O键的形成。用于不对称[（π-烯丙基）Pd]官能化的传统方法，例如引入手性膦配体，与亲电的、氧化的C2 H4活化条件不相容。此外，官能化配体BQ对于共价手性修饰是不切实际的，因为需要大量来实现最佳反应性。总的来说，这些考虑表明，这种有机金属反应不容易通过使用手性配体进行不对称诱导。
CÀH oxidation reactions have the potential to significantly streamline synthetic processes. However, to be useful for the synthesis of complex molecules, these reactions must proceed with high levels of chemo-, regio-, and stereoselectivity. Chiral bisoxazoline/copper-catalyzed systems have shown promising levels of asymmetric induction in the enantioselective allylic CÀH esterification of symmetrical, cyclic olefins. Application of these systems to complex substrates is limited by a lack of chemo-and regioselectivity as well as the need to use a large excess of reactant (4 to 10 equiv).[1] A direct allylic CÀH oxidation route would significantly increase the efficiency of producing chiral allylic esters; their syntheses generally require lengthy sequences of functional-group manipulations from preoxidized materials.[2, 3] We have recently reported a collection of mild, highly regio-and chemoselective, allylic CÀH esterification [4] and amination [5] reactions of α-olefins, and have demonstrated their utility in streamlining the synthesis of complex molecules.[6] These allylic oxidation reactions are catalyzed by PdII systems with weakly coordinating sulfoxide and quinone ligands that are poorly suited for effecting asymmetric induction.[7] Herein we disclose a novel chiral Lewis acid strategy for generating an asymmetric environment about a metal center in electrophilic, oxidative reactions that do not tolerate strongly coordinating ligands. In our approach a chiral Lewis acid is used which selectively interacts with an organopalladium intermediate to accelerate and induce asymmetry in the CÀO bond-forming step. Significantly, by using this strategy we have achieved the highest enantioselection observed to date for the allylic CÀH oxidation of terminal olefins (Scheme 1).[8] This system represents the first example of asymmetric induction from an organometallic intermediate that is effected by a chiral Lewis acid, as well as a rare example of catalytic enantioselective CÀH activation by palladium.[9]Conventional approaches toward asymmetric organometallic reactions make use of strongly coordinating chiral ligands. The oxidation of terminal olefins using 1 to give branched allylic compounds has been demonstrated to proceed by a serial ligand catalysis mechanism in which weakly coordinating bis (sulfoxide) and 1, 4-benzoquinone (BQ) ligands sequentially interact with the Pd center to promote the CÀH bond-cleavage and CÀO bond-forming steps, respectively.(Scheme 1).[4b] In theory, a chiral variant of either ligand could lead to enantioenriched products. All attempts to use chiral sulfoxides have been unsuccessful in effecting asymmetric induction. Experiments with cis-[1-D]-1-decene reveal that this ineffectiveness is due to rapid π-σ-π isomerization of the [(π-allyl) Pd] intermediate, which scrambles any chiral information imparted during the CÀH cleavage step (Scheme 1, and see the Supporting Information). We therefore set out to identify a viable alternative strategy for enantioselective CÀO bond formation. Traditional methods for asymmetric [(π-allyl) Pd] functionalization, such as the introduction of chiral phosphine ligands, are not compatible with electrophilic, oxidative CÀH activation conditions. In addition, functionalization ligand BQ is impractical for covalent chiral modification, as large amounts are required for optimal reactivity. Collectively, these considerations suggest that this organometallic reaction is not readily amenable to asymmetric induction through the use of a chiral ligand.