Nucleophilicity Parameters of Stabilized Iodonium Ylides for Characterizing Their Synthetic Potential
Nucleophilicity Parameters of Stabilized Iodonium Ylides for Characterizing Their Synthetic Potential
复制标题
DOI：
10.1021/jacs.6b05768
复制
发表时间：
2016-08-17
影响因子：
15
通讯作者：
Mayr, Herbert
中科院分区：
文献类型：
--
作者：
Chelli, Saloua;Troshin, Konstantin;Mayr, Herbert
研究了β-二羰基取代碘鎓叶立德1（a-d）与几种π共轭碳正离子和亚胺正离子的反应动力学和机理。所有的反应都是亲电试剂在滑行体的亲核碳中心进行速率控制攻击，得到碘鎓离子，碘鎓离子迅速排出碘苯并进行不同的后续反应。碘叶立德与二苯甲基离子反应的二级速率常数k（2）与二苯甲基离子的亲电性参数E线性相关，因此遵循线性自由能关系log k（20摄氏度）= s（N）（N + E）（方程式1），其中亲电体由一个参数（E）表征，而亲核体由两个参数表征：亲核性N和磁化率S-N。由这些关联式得到的碘鎓叶立德1（a-d）的亲核性参数4 < N < 8表明，在Meldrum酸或双甲酮的碳负离子中心分别用氢取代Ph-I+，使亲核性降低约10个数量级。碘鎓叶立德1（a-d）因此具有与吡咯、吲哚和甲硅烷基化烯醇醚类似的亲核性，因此应该是亚胺活化反应中合适的底物。咪唑烷酮衍生的亚胺离子Ha与碘鎓叶立德1a的环丙烷化的速率常数与通过等式1计算的速率常数的良好一致性表明了逐步机制，其中碘鎓叶立德在亚胺离子处的初始亲核攻击是速率决定性的。肉桂醛与碘鎓叶立德1a在（5S）-5-苄基-2，2，3-三甲基咪唑烷-4-酮（11 a，MacMillan的第一代催化剂）催化下的反应得到相应的环丙烷，其对映体比率为70/30，因此，提供了碘鎓叶立德是亚胺活化的环丙烷化的合适底物的原理证明。
Kinetics and mechanisms of the reactions of the beta-dicarbonyl-substituted iodonium ylides 1(a-d) with several pi-conjugated carbenium and iminium ions have been investigated. All reactions proceed with rate-determining attack of the electrophile at the nucleophilic carbon center of the glides to give iodonium ions, which rapidly expel iodobenzene and undergo different subsequent reactions. The second-order rate constants k(2) for the reactions of the iodonium ylides with benzhydrylium ions correlate linearly with the electrophilicity parameters E of the benzhydrylium ions and thus follow the linear free energy relationship log k(20 degrees C) = s(N)(N + E) (eq 1), where electrophiles are characterized by one parameter (E), while nucleophiles are characterized by two parameters: the nucleophilicity N and the susceptibility S-N. The nucleophilicity parameters 4 < N < 8 for iodonium ylides 1(a-d) derived from these correlations show that substituting hydrogen for Ph-I+ at the carbanionic center of Meldrum's acid or dimedone, respectively, reduces the nucleophilicity by approximately 10 orders of magnitude. The iodonium ylides 1(a-d) thus have nucleophilicities similar to those of pyrroles, indoles, and silylated enol ethers and, therefore, should be suitable substrates in iminium-activated reactions. Good agreement of the measured rate constant for the cydopropanation of the imidazolidinone-derived iminium ion Ha with the iodonium ylide 1a with the rate constant calculated by eq 1 suggests a stepwise mechanism in which the initial nucleophilic attack of the iodonium ylide at the iminium ion is rate-determining. The reaction of cinnamaldehyde with iodonium ylide 1a catalyzed by (5S)'-5-benzyl-2,2,3-trimethyl-imidazolidin-4-one (11a, MacMillan's first-generation catalyst) gives the corresponding cyclopropane with an enantiomeric ratio of 70/30 and, thus, provides proof of principle that iodonium ylides are suitable substrates for iminium-activated cyclopropanations.