Chiral phosphoric acid catalyzed desymmetrization of meso-1,3-diones: asymmetric synthesis of chiral cyclohexenones.
Chiral phosphoric acid catalyzed desymmetrization of meso-1,3-diones: asymmetric synthesis of chiral cyclohexenones.
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DOI：
10.1002/anie.200905271
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发表时间：
2009-12
影响因子：
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通讯作者：
K. Mori;T. Katoh;Tohru Suzuki;Takuya Noji;M. Yamanaka;T. Akiyama
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文献类型：
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作者：
K. Mori;T. Katoh;Tohru Suzuki;Takuya Noji;M. Yamanaka;T. Akiyama
环己烯酮是有机合成中的重要组成部分。特别是，Hajos-Parrish [1]和Wieland-Miescher [2]酮不仅是制备类固醇[3]的有用合成中间体，而且也是一系列天然产物的合成中间体。[4]用于获得对映体纯形式的这些酮的最容易和常规的方法是内消旋-1，3-二羰基化合物的去对称化，其中（S）-脯氨酸通常用作高度可靠的手性催化剂（方案1）。[1，2]该方案由两个连续的转化组成：1）通过（S）-脯氨酸催化的羟醛缩合反应使meso-1，3-二酮去对称化，以及2）脱水。由于我们的初步发现，[5]衍生自（R）-BINOL的手性磷酸1作为多功能手性布朗斯台德酸催化剂已被广泛研究。它们在与亚胺的亲核加成、与α，β-不饱和化合物的1，4-加成以及与Hantzsch酯的转移氢化反应中均表现出显著的不对称诱导能力。[6]虽然Antilla及其同事已经报道了通过手性磷酸的方式使meso-aziridines不对称开环[7a]，但是手性磷酸诱导的meso-1，3-二酮的去对称化仍然是一个挑战。[7b与通过共价键（（S）-脯氨酸催化）的控制相比，通过弱的非共价键相互作用（氢键）控制立体选择性不是一个微不足道的问题。[8]本文报道了在手性磷酸的诱导下，通过内消旋-1，3-二羰基化合物的去对称化反应合成手性环己烯酮。[9]该方法可一步一锅完成1，3-二酮化合物的去对称化和脱水反应，得到对映选择性良好的手性环己烯酮。通过在甲苯中用10摩尔%的1a处理三酮2进行初步研究。令人满意的是，获得了对映体富集形式的烯酮3a（46%ee;表1，
Cyclohexenones are important building blocks in synthetic organic chemistry. In particular, Hajos–Parrish [1] and Wieland–Miescher [2] ketones are useful synthetic intermediates not only for the preparation of steroids [3] but also for a range of natural products.[4] The most facile and conventional method used to obtain these ketones in enantiomerically pure form is the desymmetrization of meso-1, 3-dicarbonyl compounds, in which (S)-proline is commonly used as a highly reliable chiral catalyst (Scheme 1).[1, 2] This protocol consists of two consecutive transformations: 1) desymmetrization of meso-1, 3-dione by (S)-proline-catalyzed aldol reaction, and 2) dehydration.As a result of our initial findings,[5] chiral phosphoric acids 1 derived from (R)-BINOL have been extensively studied as versatile chiral Brønsted acid catalysts. They exhibited remarkable asymmetric inducing ability in the nucleophilic addition to imine, the 1, 4-addition to α, β-unsaturated compounds, and the transfer hydrogenation with Hantzsch ester.[6] Although the asymmetric ring-opening of meso-aziridines by means of chiral phosphoric acid had already been reported by Antilla and co-workers,[7a] the chiral phosphoric acid induced desymmetrization of meso-1, 3-diones still remains a challenge.[7b, c] The control of stereoselectivity by weak, noncovalent bond interaction (hydrogen bond) is not a trivial issue in comparison with the control by covalent bonds ((S)-proline catalysis).[8] Herein, we report the asymmetric synthesis of synthetically useful chiral cyclohexenones through the desymmetrization of meso-1, 3-dicarbonyl compounds induced by a chiral phosphoric acid.[9] By this method, both desymmetrization of the 1, 3-dione compound and dehydration could be accomplished in a single-step, one-pot operation, to afford chiral cyclohexenones with excellent enantioselectivity. An initial study was conducted by treatment of triketone 2 with 10 mol% of 1a in toluene. Gratifyingly, enone 3a was obtained in the enantioenriched form (46% ee; Table 1,