Pyridine Core Activation via 1,5-Electrocyclization of Vinyl Pyridinium Ylides Generated from Bromo Isomerized Morita−Baylis−Hillman Adduct of Isatin and Pyridine: Synthesis of 3-Spirodihydroindolizine Oxindoles

Abstract

An activation of the pyridine nucleus has been achieved via 1,5-electrocyclization of vinyl pyridinium ylides generated from bromo isomerized Morita-Baylis-Hillman adducts of isatin and pyridine under basic conditions. The method has been successfully applied for an efficient synthesis of a number of 3-spirodihydroindolizine-2-oxindoles, which have been found as core structure of secoyohimbane and heteroyohimbane alkaloid natural products.

Recent Progress on Routes to Spirooxindole Systems Derived from Isatin

“…The isomerized bromides of Morita–Baylis–Hillman isatin adducts with electron‐poor alkenes could be exploited to develop diversified spirooxindole systems through intramolecular 1,5‐electrocyclization of vinyl pyridinium ylides , [3 + 2] annulation based on in situ phosphorus ylide intermediates , acid‐catalyzed lactonisation of their formaldehyde adducts , reductive cyclization with sodium borohydride , and so on. The corresponding products of 3‐spiro‐dihydroindolizine‐2‐oxindoles ( 52 ), 3‐spirocyclopentene‐2‐oxindoles ( 53 ), α‐methylene‐γ‐butyrolactone‐3‐spiro‐oxindolones ( 54 ), and 3‐spirocyclopropane‐2‐indolones ( 55 ) would be generated, respectively (Scheme ).…”

Palladium-catalyzed approach to the synthesis of five-membered O-heterocycles

“…The allenepalladium complex, formed initially, suffered a nucleophilic attack by the bromide to produce a σ-allylpalladium species, which rapidly equilibrated with the corresponding (π-allyl)palladium intermediate which underwent intramolecular cycloetherification to afford the spirocompound (Scheme 121) [256,179].…”

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

“…Isatin and its derivatives may be the most useful starting materials or precursors in the synthesis of a wide number of spirocyclic oxindoles [7–8]. Due to its simple process, easy operation, efficiency and high atomic economy, the multicomponent reaction based on isatin and its derivatives have become an efficient method for the synthesis of various spirooxindoles in recent years [9–10]. It is known that the multicomponent reactions of isatins with in situ formed azomethine ylides have become the efficient synthetic procedure for constructing versatile spirooxindole systems [11–14].…”