A Short and Efficient Synthesis of 3-Spiro-α-methylene-γ-butyrolactone Oxindolones from Isomerised Bromo Derivatives of Morita-Baylis-Hillman Adducts

Abstract

A short and efficient synthesis of a-methylene-g-butyrolactone-3-spirooxindolones by the reaction of isomerised bromo derivatives of Morita-Baylis-Hillman adducts of isatin and formaldehyde followed by acid-catalysed lactonisation has been achieved. The oxindolidino allyl bromide has been used for the first time for the allylation of aldehydes to afford a 2-oxindolidino homoallylic alcohol which on acid-catalysed lactonisation delivered the title compounds in excellent yield. Synthetic transformation of the spirolactone oxindole is demonstrated with the preparation of an oxirane derivative and a second Morita-Baylis-Hillman adduct.

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 ).…”

Recent Contributions from the Baylis−Hillman Reaction to Organic Chemistry

“…The reaction sequence involves the preparation of the tetra-substituted alkenes ( 433 ) via the treatment of Baylis−Hillman alcohols with CH(OMe) 3 or benzene or propargyl alcohol followed by reaction with formaldehyde in the presence of DABCO and subsequent cyclization following the reaction sequence described in Path A (Scheme ). Subsequently, Shanmugam and Viswambharan also reported an efficient synthesis of 3-spiro-α-methylene-γ-butyrolactone-oxindolones from the allyl bromide derivatives (isomerized) of Baylis−Hillman alcohols obtained from isatin derivatives and methyl acrylate via reaction with formaldehyde in the presence of indium followed by cyclization (Path B, Scheme ).…”

Organoindium Reagents: The Preparation and Application in Organic Synthesis

“…When oxindolidino allyl bromide was treated with 40% aqueous formaldehyde and indium in DMF, a Barbier-type allylation occurred to deliver 2-oxindolidino homoallylic alcohol as the major product (Scheme ) . Upon exposure of the resulting hydroxyester to p -toluenesulfonic acid (PTSA)-catalyzed lactonization, a biologically and pharmaceutically attractive α-methylene-γ-butyrolactone-3-spirooxindolone product was produced in 78% yield.…”