Substrate-Controlled Regioselectivity Switchable [3 + 2] Annulations To Access Spirooxindole Skeletons

Abstract

The additive-free [3 + 2] annulation from isatins, amino acids with 2-styrylbenzoxazoles, was described, providing a series of functional and structurally complex 3,3′-pyrrolidinyl-spirooxindole derivatives containing four contiguous and two quaternary stereogenic centers in high yields (up to 95%) and excellent diastereoselectivities (up to >25:1 dr). Interestingly, the reaction exhibits switchable regioselectivity depending on the substrate of amino acids. With proline or thioproline as the substrate, the reaction afforded α-regioselective spirooxindole skeletons. In contrast, when piperidine acid is the substrate, the reaction provided γ-regioselective spirooxindole skeletons.

Dipolarophile-Controlled Regioselective 1,3-Dipolar Cycloaddition: A Switchable Divergent Access to Functionalized N-Fused Pyrrolidinyl Spirooxindoles

“…In this context, the scaffolds of N -fused pyrrolidinyl spirooxindoles can be regulated and switched via the dipole-controlled or dipolarophile-controlled strategy. To date, several powerful dipole-controlled multicomponent 1,3-dipolar cycloadditions have been explored selectively to access N -fused pyrrolidinyl spirooxindoles by using diverse α -amino acids as precursors to furnish isatin-derived azomethine ylides [ 40 , 56 , 57 , 58 , 59 ] ( Scheme 1 b). Noticeably, 1,4-enedione derivatives [ 60 , 61 , 62 ], such as maleimides [ 63 , 64 ], methylene indolinones [ 65 , 66 , 67 ], 1,4-naphthoquinone [ 68 , 69 , 70 , 71 ], maleic anhydride, etc., can be activated by two carbonyl groups, which can enhance the flexibility and diversity of cyclization in synthetic chemistry.…”

Gold‐Catalyzed Formal [4+2] Cycloaddition as Access to Antitumor‐Active Spirocyclic Oxindoles from Alkynes and Isatin‐Derived Ketimines

“…For instance, Lapatin B shows potent inhibitory activity against the aquabacterial V, [15] Surugatoxin exhibits a ganglionic blocker of nicotinic acetylcholine receptors [16] and NITD 609 as anti‐malarial species inhibits protein synthesis in plasmodium falciparum (Figure 1). [8,10a,17] …”

Goldkatalysierte formale [4+2]‐Cycloaddition als Zugang zu antitumoraktiven spirozyklischen Oxindolen aus Alkinen und von Isatin abgeleiteten Ketiminen

“…Beispielsweise zeigt Lapatin B eine starke Hemmwirkung gegen das Aquabakterium V, [15] Surugatoxin wirkt als Ganglienblocker nikotinischer Acetylcholinrezeptoren [16] und NITD 609 hemmt als Anti‐Malaria‐Spezies die Proteinsynthese in Plasmodium falciparum (Abbildung 1). [8,10a,17] …”