Neighboring Group Participation of Phosphine Oxide Functionality in the Highly Regio- and Stereoselective Iodohydroxylation of 1,2-Allenylic Diphenyl Phosphine Oxides

Two sets of reaction conditions were established to enable the highly regio- and stereoselective iodohydroxylation of 1,2-allenylic diphenyl phosphine oxides, yielding (E)-2-iodo-3-hydroxy-1-alkenyl diphenyl phosphine oxides with very high stereoselectivity. The scope of this reaction was examined extensively. Notably, studies on the reactivity of optically active substrates indicated that the axial chirality in the starting allenes may be efficiently transferred to the center chirality of the products with no discernible loss of enantiopurity. Due to the importance of phosphine-containing compounds, both as reagents and ligands, this reaction shows potentials in organic synthesis. Investigations using ESI-MS technology on the 18O-labeled product, which was prepared using 18O-water as the solvent, indicated that the 18O atom was bound to phosphorus in the final product and the oxygen atom of the hydroxyl comes from the phosphinyl functionality of the allene reactant. These results provided solid evidence for the formation of a five-membered cyclic intermediate from the neighboring group participation of the diphenylphosphinyl group. To the best of our knowledge, this is the first time that the neighboring group participation of this type of group was observed.

本研究建立了两套反应条件，可实现1,2-联烯型二苯基氧化膦（1,2-allenylic diphenyl phosphine oxides）的高区域与立体选择性碘羟基化反应，以极高立体选择性得到(E)-2-碘-3-羟基-1-烯基二苯基氧化膦（(E)-2-iodo-3-hydroxy-1-alkenyl diphenyl phosphine oxides）。本研究对该反应的底物适用范围进行了全面考察。值得注意的是，对手性底物的反应活性研究表明，原料联烯的轴手性可高效转移至产物的中心手性，且未出现可检测的对映体纯度损失。鉴于含膦化合物作为试剂与配体的重要应用价值，该反应在有机合成中具有良好的应用潜力。研究人员以18O标记水为溶剂制备了18O标记产物，并通过电喷雾电离质谱（ESI-MS, Electrospray Ionization Mass Spectrometry）对其进行分析，结果显示最终产物中的18O原子与磷原子结合，而羟基中的氧原子来源于原料联烯的氧膦基官能团。上述结果为二苯基氧膦基通过邻基参与形成五元环中间体的反应路径提供了确凿证据。据我们所知，此类基团的邻基参与现象此前尚未被正式报道。