Copper(I)-Catalyzed Intramolecular Asymmetric Double C-Arylation for the Formation of Chiral Spirocyclic Bis-oxindoles

Abstract

A copper-catalyzed intramolecular asymmetric double C-arylation reaction was developed. The method provides a facile approach to chiral spiro bis-oxindoles in high yields and with good to excellent enantioselectivities. It also shows a broad substrate scope and good functional group tolerance. Density functional theory (DFT) calculations were conducted and revealed that the enantioselectivity is determined at the oxidative addition of Cu(I) into the second C−I bond.

A Synthesis of Spirooxindole‐Isoindolinones Through Ugi Reaction Followed by Copper‐Catalyzed Tandem C−N/C−C Coupling Process

“…To our delight, better outcome was obtained by using DMSO as solvent and the desired product 5 a was delivered in 78% yield (Table 1, entry 7). Other bases, such as tBuONa, NaH, NaOH, Cs 2 CO 3 , K 2 CO 3 were further screened and all delivered inferior results (Table 1, entries [11][12][13][14][15].…”

“…During our continuous efforts in the development of copper catalyzed coupling and tandem reactions, [13] we became intrigued by the possibility of synthesis of spirooxindole-isoindolinones through Ugi reaction followed by copper-catalyzed tandem CÀ N/CÀ C coupling process. We envisaged that the copper catalyst system might be different from palladium and participate in both CÀ N and CÀ C bond formation steps, accordingly higher reaction temperature could be prevented (Scheme 1b).…”

Development of a C2-Symmetric Chiral aza Spirocyclic Diol

“…15 In addition, recently Cai and co-workers developed a copper(I)-catalyzed intramolecular asymmetric double C-arylation for the synthesis of diverse enantioenriched spirooxindoles. 16 As outlined in Scheme 2, our synthesis starts from commercially available 7-hydroxy-3,4-dihydroquinolin-2(1H)one 1. The secondary amine 2 was prepared by reduction of 1 with LiAlH 4 .…”

“…Later, this reaction was achieved highly enantioselectively with a chiral organoiodine catalyst by Gong and co-workers . In addition, recently Cai and co-workers developed a copper­(I)-catalyzed intramolecular asymmetric double C-arylation for the synthesis of diverse enantioenriched spirooxindoles …”

Construction of Spiro Skeletons in 2,2',3,3'-Tetrahydro-1,1'- spirobi[1H-indene]-7,7'-diol (SPINOL) and Analogues

“…研究表明, 2-碘代间苯二酚衍生的手性催化剂分子 中脯氨酸甲酯结构在实现高对映选择性诱导时发挥了 关键作用, N 1 ,N 3 -二苯基丙二酰胺反应物分子中苯环上 的取代基对产率和光学纯度有着不同程度的影响, 4-位 强给电子基团会很大程度降低螺环产物的产率和对映 选择性. 2019 年, 蔡倩课题组 [36] 报道了铜配合物催化下 对映选择性合成螺吲哚酮的反应, 扩展了芳环上取代基 的种类, 合成了多种芳环结构的螺吲哚酮类产物(Eq. 8).…”