Stereoselective Reaction for Construction of Quaternary Carbon Center and its Application to the Syntheses of Pyrrolidino[2,3-b]indoline Natural Products

The pyrrolino [2,3–b] indoline ring system bearing an allylic moiety at the 3a–site is a widely distributed structural framework present in a number of biologically active natural products. In view of the potential of these compounds as a lead compound to new and more biologically active agents, a development of diversely and efficiently synthetic methods for pyrrolino [2,3–b] indolines and analogues is essential. This review describes an efficient methodology for construction of pyrrolino [2,3–b] indoline architecture through a domino reactions, Horner–Wadsworth–Emmons olefination of 2–allyloxy–3–indolinone, isomerizetion, Claisen rearrangement and a reductive cyclization of oxindoles having C2N and allylic units at 3–site. This methodology was applied to total syntheses of the related natural products, pseudophrynaminol and flustramine A–C. Furthermore, total syntheses of pyrazino [2′,1′–5,1] pyrrolino [2,3–b] indoline natural products, fructigenine A and 5–N–acetylardeemin through Ugi reaction and cyclization are also illustrated.