【摘要】 设计了azaheptafulvenes作为偶极子与N-Boc-3-烯基吲哚酮反应,用来构建螺环[吡咯烷-3,3’-吲哚酮]衍生物.在1mol%手性氮氧-Ni(II)配合物催化剂条件下,该不对称[8+2]环加成反应以高的收率(90%~99%收率),好的非对映选择性(高达97∶3 dr)和优异的对映选择性(92%~99%ee)得到手性环庚三烯并螺环[吡咯烷-3,3’-吲哚酮]衍生物.更多还原

【Abstract】 The spiro pyrrolidin-3,3’-oxindole core is a privileged skeleton that is found in many natural products and biologically active molecules. For its construction, the [3+2] cycloaddition of 2π component 3-alkenyl-oxindoles with 3π component azomethine ylides is one of the most effective strategies. Since the pioneering work of Gong and co-workers, great effort has been devoted to the development of asymmetric [3+2] cycloadditions with azomethine ylides as the dipole synthon, and impressive progress has been achieved. In contrast, there is no report about higher-order [8+2] cycloaddition of 3-alkenyl-oxindoles with azaheptafulvenes as the 8π dipole synthons, which is an effective way to build cycloheptatriene-fused pyrrolidin-3,3’-oxindole derivatives with three contiguous stereocenters, including a spiro-quaternary chiral carbon atom. Herein, the azaheptafulvenes is developed as a new dipole synthon with 3-alkenyl-oxindoles to construct pyrrolidin-3,3’-oxindoles derivatives for the first time. In the presence of 1 mol% of chiral N,N’-dioxide L6-Ni(II) complex, the asymmetric [8+2] cycloaddition performs well, affording functionalized cycloheptriene-fused pyrrolidin-3,3’-oxindoles derivatives in excellent yields(90%~99%), diastereoselectivities(up to 97∶3 dr), and enantioselectivities(92%~99% ee) under mild conditions. A representative procedure for the asymmetric [8+2] cycloaddition is as follows: to a test tube, the catalyst solution(1 mol%, in THF) was added, and the THF was evaporated by oil pump. N-Boc-3-alkenyl-oxindole 2a and 0.5 mL of CH2Cl2 were added sequentially under air(N2 atmosphere is not necessary). The reaction solution was stirred at 35 ℃ for 0.5 h, then the 8π component azaheptafulvene 1a(1.05 equiv.) was added. The mixture continued stirring at 35 ℃until N-Boc-3-alkenyl-oxindole 2a was consumed(detected by TLC). Finally, the corresponding product 3a was purified by flash chromatography on basic Al2O3 [V(petroleum)/V(CH2Cl2)/V(EtOAc)=8∶8∶1].更多还原