EFFICIENT CATALYTIC ASYMMETRIC ALKYLATIONS .3. A KINETIC AND MECHANISTIC STUDY OF THE ENANTIOSELECTIVE PHASE-TRANSFER METHYLATION OF 6,7-DICHLORO-5-METHOXY-2-PHENYL-1-INDANONE
EFFICIENT CATALYTIC ASYMMETRIC ALKYLATIONS .3. A KINETIC AND MECHANISTIC STUDY OF THE ENANTIOSELECTIVE PHASE-TRANSFER METHYLATION OF 6,7-DICHLORO-5-METHOXY-2-PHENYL-1-INDANONE
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DOI：
10.1021/jo00230a017
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发表时间：
1987-10-16
影响因子：
3.6
通讯作者：
GRABOWSKI, EJJ
中科院分区：
文献类型：
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作者：
HUGHES, DL;DOLLING, UH;GRABOWSKI, EJJ
在50%NaOH/甲苯体系中，用MeCl对6，7-二氯-5-甲氧基-2-苯基-1-茚满酮进行相转移甲基化反应，合成了甲基化茚满酮2，ee值高达94%。溶剂，烷基化剂，温度和催化剂的影响进行了研究：非极性溶剂得到较高的ee比极性溶剂; MeCl得到了较高的ee比MeBr和梅尔;和温度对反应的影响不大。N-苄基辛可宁卤化物催化剂的log ee/ee 0与a的Hammett图给出反应常数p为0.21，ee范围为60%至94%，表明具有增加吸电子能力的取代基改善催化剂选择性。对该反应的动力学和机理研究揭示了几个不寻常的特征。在50%NaOH/甲苯中，这些反应包括：（1）茚满酮1在界面处脱质子化，形成烯醇钠作为单独的固相;（2）取代的IV-苄基辛可宁催化剂作为二聚体萃取到有机层中;（3）在MeCl中的动力学级数为0.7，在催化剂中为0.55。在30%NaOH/甲苯体系中，（1）不生成固体烯醇化物;（2）手性甲基化反应的催化剂级数为0.5，外消旋甲基化反应的催化剂级数为1.0。烯醇化物的碳-碳键形成反应是不对称合成的一个重要领域。酮的立体定向烷基化反应有三种方法：（1）三步反应，包括制备手性中间体（亚胺、腙等）;中间体的烷基化和烷基化中间体水解成酮; 2（2）烯醇化物与具有手性离去基团的烷基化剂的反应; 3和（3）涉及手性催化剂的相转移烷基化。4手性辅助路线的工作始于20世纪60年代，5但仅在最近十年才取得成功（> 90% ee）。2.尽管取得了这些成就，但这一办法仍有一些固有的缺点。该程序需要三个步骤，并使用化学计量的手性助剂，这往往必须合成。使用手性离去基团
The phase-transfer methylation of 6, 7-dichloro-5-methoxy-2-phenyl-l-indanone by MeCl in 50% NaOH/toluene using substituted N-benzylcinchoninium halides has provided the methylated indanone 2 in ee’s up to 94%. The effects of solvent, alkylating agent, temperature, and catalyst were investigated: nonpolar solvents gave higher ee’s than polar solvents; MeCl gave a higher ee than did MeBr and Mel; and temperature had little effect on the reaction. A Hammett plot of log ee/ee0 vs. a for the N-benzylcinchoninium halide catalysts gave a reaction constant p of 0.21 with an ee range of 60% to 94%, demonstratingthat substituents with increasing electron-withdrawing power improve catalyst selectivity. A kinetic and mechanistic study of the reaction has revealed several unusual features. In 50% NaOH/toluene these includethe following:(1) the indanone 1 is deprotonated at the interface to form the sodium enolate as a separate solid phase;(2) the substituted IV-benzylcinchoninium catalysts are extracted into the organic layer as dimers; and (3) the kinetic order in MeCl is 0.7 and in catalyst is 0.55. In 30% NaOH/toluene the following obtain:(1) no solid enolate is formed;(2) an order in catalyst of 0.5 was found for the chiral methylation pathway, while an order of 1.0 was found for the racemic methylation pathway.Much recent synthetic methodology has beendevoted to developing and understanding asymmetric reactions in an effort to provide direct, efficient, and economical routes to target compounds. Carbon-carbon bond-forming re-actions of enolates are one important area of asymmetric synthesis. The stereospecific alkylation of ketones has been approached in three ways:(1) the three-step se-quence involving preparation of a chiral intermediate (imine, hydrazone, etc.), alkylation of the intermediate, and hydrolysis of the alkylated intermediate to the ketone; 2 (2) reaction of an enolate with an alkylating agent having a chiral leaving group; 3 and (3) phase-transfer alkylation involving a chiral catalyst. 4 Work on the chiral auxiliary route began in the 1960s, 5 but only in the last decade has success(> 90% ee) been achieved. 2 Despite these achievements, some drawbacks are inherent in this approach. The procedures require three steps and the use of stoichiometric quantities of chiral auxiliaries, which often must be synthesized. Using the chiral leaving group