Department Chemie , Ludwig-Maximilians-Universität München , Butenandtstrasse 5-13 , 81377 München , Germany.
J Am Chem Soc. 2018 Apr 25;140(16):5500-5515. doi: 10.1021/jacs.8b01657. Epub 2018 Apr 16.
The kinetics of epoxide formation by Darzens condensation of aliphatic ketones 1 with arylsulfonyl-substituted chloromethyl anions 2 (ArSOCHCl) have been determined photometrically in DMSO solution at 20 °C. The reactions proceed via nucleophilic attack of the carbanions at the carbonyl group to give intermediate halohydrin anions 4, which subsequently cyclize with formation of the oxiranes 3. Protonation of the reaction mixture obtained in THF solution at low temperature allowed the intermediates to be trapped and the corresponding halohydrins 4-H to be isolated. Crossover experiments, i.e., deprotonation of the halohydrins 4-H in the presence of a trapping reagent for the regenerated arylsulfonyl-substituted chloromethyl anions 2, provided the relative rates of backward ( k) and ring closure ( k) reactions of the intermediates. Combination of the kinetic data ( k) with the splitting ratio ( k/ k) gave the second-order rate constants k for the attack of the carbanions 2 at the ketones 1. These k values and the previously reported reactivity parameters N and s for the arylsulfonyl-substituted chloromethyl anions 2 allowed us to use the linear free energy relationship log k(20 °C) = s( N + E) for deriving the electrophilicity parameters E of the ketones 1 and thus predict potential nucleophilic reaction partners. Density functional theory calculations of the intrinsic reaction pathways showed that the reactions of the ketones 1 with the chloromethyl anions 2 yield two rotational isomers of the intermediate halohydrin anions 4, only one of which can cyclize while the other undergoes retroaddition because the barrier for rotation is higher than that for reversal to the reactants 1 and 2. The electrophilicity parameters E correlate moderately with the lowest unoccupied molecular orbital energies of the carbonyl groups, very poorly with Parr's electrophilicity indices, and best with the methyl anion affinities calculated for DMSO solution.
脂肪族酮 1 与芳基磺酰取代的氯甲基阴离子 2（ArSOCHCl）的 Darzens 缩合形成环氧化物的动力学已在 20°C 的 DMSO 溶液中通过光度法确定。反应通过碳负离子在羰基处的亲核攻击进行，得到中间体卤代醇阴离子 4，随后通过形成环氧化物 3 进行环化。在低温下在四氢呋喃溶液中对反应混合物进行质子化，允许捕获中间体并分离相应的卤代醇 4-H。交叉实验，即在存在用于再生芳基磺酰取代的氯甲基阴离子 2 的捕获试剂的情况下对卤代醇 4-H 进行脱质子化，提供了中间体的反向（k）和环闭合（k）反应的相对速率。动力学数据（k）与分裂比（k/k）的组合给出了碳负离子 2 攻击酮 1 的二级速率常数 k。这些 k 值和先前报道的芳基磺酰取代的氯甲基阴离子 2 的反应性参数 N 和 s 允许我们使用线性自由能关系 log k（20°C）= s（N + E）来推导酮 1 的亲电参数 E，从而预测潜在的亲核反应伙伴。固有反应途径的密度泛函理论计算表明，酮 1 与氯甲基阴离子 2 的反应生成中间体卤代醇阴离子 4 的两种旋转异构体，只有一种可以环化，而另一种则发生反加成，因为旋转的势垒高于反转回到反应物 1 和 2 的势垒。亲电性参数 E 与羰基的最低未占据分子轨道能量中等相关，与 Parr 的亲电性指数相关性很差，与计算 DMSO 溶液中甲基阴离子亲和力的相关性最好。
