First example of a highly enantioselective catalytic protonation of silyl enol ethers using a novel Lewis acid-assisted Bronsted acid system
First example of a highly enantioselective catalytic protonation of silyl enol ethers using a novel Lewis acid-assisted Bronsted acid system
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DOI：
10.1021/ja962414r
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发表时间：
1996-12-18
影响因子：
15
通讯作者：
Yamamoto, H
中科院分区：
文献类型：
--
作者：
Ishihara, K;Nakamura, S;Yamamoto, H
近年来，利用化学计量或催化量的手性质子源对烯醇化物进行对映选择性质子化反应是合成化学中最有用的进展之一。在大多数这些反应中，金属烯醇化物在碱性或中性条件下使用。我们最近报道了一种光学活性的联萘酚（BINOL）-四氯化锡配合物1是一种高效的手性质子源，用于前手性甲硅烷基烯醇醚的对映选择性质子化，这是一种可分离的烯醇或烯醇化物的合成等价物。[3]我们将这种活化的质子源称为刘易斯酸辅助的布朗斯台德酸或LBA。3我们在这里报道了一种新的手性LBA 2用于前手性三甲基硅烯醇醚的不对称选择性质子化的催化体系。2使用LBA的对映选择性质子化的催化循环的基本原理概述于方案1中。该催化循环的前提是：（1）在用手性LBA质子化甲硅烷基烯醇醚后，手性质子源必须通过从非手性质子源转移一个质子而再生，而非手性质子源必须通过从甲硅烷基烯醇醚转移一个甲硅烷基而转化为甲硅烷基醚;（2）四氯化锡必须主要与手性质子源配位;（3）由非手性质子源和四氯化锡生成的LBA的反应活性必须远低于手性质子源或其LBA的反应活性。在上述工作假设的基础上，我们实现了LBA催化的外消旋2-苯基环己酮三甲基硅烯醇醚3的不对称质子化反应。代表性结果总结见表1。在甲苯中，在化学计量量的四氯化锡作为刘易斯酸和2，6-二甲基苯酚（5）作为非手性质子源的存在下，3与（R）-2-羟基-2 ′-甲氧基-1，1 ′-联萘（BINOL-Me）（2-5 mol%）的质子化被加速并在空间上被控制以形成具有高对映选择性的酮4（条目1和2）。尽管在催化使用（R）-BINOL的情况下观察到类似的结果，但所得的对映选择性仅为中等（条目3）。化合物5是所筛选的多种芳族醇中最有效的非手性质子源，所述芳族醇包括2，4，6-三甲基苯酚、2，6-二乙基苯酚、2，6-二异丙基苯酚和4-溴-2，6-二甲基苯酚。虽然四氯化锡有效地促进了
The recent development of the enantioselective protonation of enolates using stoichiometric or catalytic amounts of chiral proton sources has been one of the most useful advances in synthetic chemistry. 1, 2 In most of these reactions, metal enolates are used under basic or neutral conditions. We recently reported that an optically active binaphthol (BINOL)-tin tetrachloride complex 1 is a highly effective chiral proton source for enantioselective protonation of a prochiral silyl enol ether, which is an isolable synthetic equivalent of enol or enolate. 3 We refer to this activated proton source as a Lewis acid-assisted Brønsted acid or LBA. 3 We report here catalytic systems for the enantioselective protonation of prochiral trimethylsilyl enol ethers using a novel chiral LBA 2. 2The rationale for the catalytic cycle for enantioselective protonation using LBA is outlined in Scheme 1. The catalytic cycle presupposes the following:(1) after protonation of silyl enol ethers with chiral LBA, the chiral proton source must be regenerated by the transfer of a proton from the achiral proton source while the achiral proton source is transformed to a silyl ether by the transfer of a silyl group from silyl enol ether;(2) tin tetrachloride must be predominantly coordinated to the chiral proton source;(3) the reactivity of LBA generated from the achiral proton source and tin tetrachloride must be much lower than that of the chiral proton source or its LBA. On the basis of the above working hypothesis, we realized the LBA-catalyzed enantioselective protonation of trimethylsilyl enol ether 3 derived from racemic 2-phenylcyclohexanone. Representative results are summarized in Table 1. In the presence of stoichiometric amounts of tin tetrachloride as a Lewis acid and 2, 6-dimethylphenol (5) as an achiral proton source in toluene, the protonation of 3 with (R)-2-hydroxy-2′-methoxy-1, 1′-binaphthyl (BINOL-Me)(2-5 mol%) was accelerated and controlled sterically to form ketone 4 with high enantioselectivity (entries 1 and 2). Although a similar result was observed with the catalytic use of (R)-BINOL, the resulting enantioselectivity was only moderate (entry 3). Compound 5 was the most effective achiral proton source among a variety of aromatic alcohols screened, including 2, 4, 6-trimethylphenol, 2, 6-diethylphenol, 2, 6-diisopropylphenol, and 4-bromo-2, 6-dimethylphenol. While tin tetrachloride efficiently promoted