Paton Robert S, Goodman Jonathan M, Pellegrinet Silvina C
Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
J Org Chem. 2008 Jul 4;73(13):5078-89. doi: 10.1021/jo8007463. Epub 2008 Jun 11.
To rationalize the experimental results observed in the asymmetric conjugate addition of alkenylboronates to enones catalyzed by binaphthols and shed light into the factors controlling the rate, the selectivity, and the substituent effects of this process, a theoretical DFT study has been performed. The calculations suggest the catalytic cycle is finely balanced. Reversible exchange of methoxy ligands gives rise to the binaphthol-derived alkenylboronate, which is highly Lewis acidic and strongly coordinates to the enone carbonyl in a reversible fashion, lowering the energy barrier for the subsequent conjugate addition step. The key asymmetric step goes through a sofalike transition structure in which the boron atom is strongly bound to the carbonyl oxygen and lies in the plane of the enone moiety. A steric clash between one of the iodine atoms of the ligand and one face of the enone seems to be responsible for the facial discrimination. The alternative reaction channel in which only one methoxy ligand of the alkenylboronate is exchanged was investigated too and was computed to be disfavored. The [4 + 2] and the [4 + 3] pathways for the competitive hetero-Diels-Alder reaction were also found to be disfavored relative to the conjugate alkenylboration. In addition, the effects of substitution on the enone and the alkenylboronate have been evaluated. Calculations correctly reproduced the experimental reactivity trends and enantiomeric ratios.
为了使在联萘酚催化的烯基硼酸酯与烯酮的不对称共轭加成中观察到的实验结果合理化，并深入了解控制该反应速率、选择性和取代基效应的因素，进行了一项理论密度泛函理论（DFT）研究。计算结果表明催化循环处于精细平衡状态。甲氧基配体的可逆交换产生了联萘酚衍生的烯基硼酸酯，其具有高度的路易斯酸性，并以可逆方式与烯酮羰基强烈配位，降低了后续共轭加成步骤的能垒。关键的不对称步骤通过一个类似沙发的过渡结构，其中硼原子与羰基氧紧密结合并位于烯酮部分的平面内。配体的一个碘原子与烯酮的一个面之间的空间冲突似乎是造成面选择性的原因。还研究了烯基硼酸酯中仅一个甲氧基配体发生交换的替代反应通道，并计算得出该通道不利。相对于共轭烯基硼化反应，竞争性杂狄尔斯-阿尔德反应的[4 + 2]和[4 + 3]途径也被发现不利。此外，还评估了烯酮和烯基硼酸酯上取代基的影响。计算结果正确地再现了实验反应活性趋势和对映体比例。
