Palladium Catalyzed Annulation of Morita‐Baylis‐Hillman Adducts: Synthesis of Indene and Indanone Derivatives

Abstract

Concise and efficient methods for the syntheses of functionalized Indene and Indanone derivatives from Morita-Baylis Hillman (MBH) alcohols via Palladium catalyzed annulations are described. The formation and nature of the product was based on the MBH adduct used and the reaction conditions established after detailed optimization studies. The reaction of Baylis-Hillman alcohols (1 a-m) in presence of Pd(OAc) 2 (5 mol %), P(o-Tol) 3 (20 mol %) , AgOAc (1 eq.) and Na 2 CO 3 (2 eq.) in Dioxane at 120°C under Nitrogen atmosphere provided substituted indenes (2 a-m) in good to excellent yields. While, Indanone derivatives (4 a-f) are obtained from o-halo substituted MBH adducts (3 a-l) when subjected to reaction with Pd (OAc) 2 (3 mol %) and K 3 PO 4 (2.5 eq.) in DMA at 140°C in the absence of any ligand or additive.

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF3·OEt2 catalysis

“…The steric hindrance and electronic effect of electron-withdrawing substituents such as nitriles and methyl/ethyl esters did not significantly affect the scope of the reaction. On contradictory to the literature reports [Cr(III)salenCl] complex surprisingly catalysed the intramolecular Friedel–Crafts reaction in electron deactivated arenes of MBH adducts [ 10 – 14 ]. However, ortho / meta -substituted arenes of MBH adducts were inert to the Cr(salen)/BF 3 ·OEt 2 catalytic system ( 5m – r , Table 2 ).…”

“…Operating FC reactions in versatile synthons such as Morita–Baylis–Hillman (MBH) adducts is a challenging process. Inter/intramolecular Friedel–Crafts reactions of Morita–Baylis–Hillman adducts leads to a variety of products such as quinolinones [ 8 ], cycloheptene-6-carboxylates [ 9 ], indenes [ 10 – 13 ] and indanones [ 14 ]. However, most of the reported Friedel–Crafts reactions utilize either strong Lewis acid catalysts or severe reaction conditions resulting in low yield, unwanted byproducts and tedious workup methodologies [ 15 – 16 ].…”

“…Thereafter Lee et al [ 12 ] and Xu et al [ 13 ] synthesised indenes in presence of a palladium catalyst from allylic acetates of MBH adducts. Recently Anas et al [ 14 ] has reported the palladium-catalysed synthesis of indene from MBH adducts at 120 °C under N 2 atmosphere. The methodologies referred in Scheme 1 access indenes either relying on harsh reaction conditions or on the dialkoxy and ortho -halide- substituted MBH adducts.…”

Recent Advances in Transition Metal‐Catalyzed Domino‐Cyclization Strategies for Functionalized Heterocyclic/Carbocyclic Compounds

“…Similarly, indanone derivatives also have a wide range of applications in medicinal, and agricultural areas and natural product synthesis. Some potential drugs are composed of structural analogues of indanone [97] . In 2002, Tietze et al.…”

Microwave-accelerated and benzoyl peroxide (BPO)-initiated cyclization of 1,5-enynes having cyano groups with cyclic alkanes under metal-free conditions

“…1). In the past few decades, many methods have been developed for synthesizing exocyclic indan derivatives, with these methods including the Wittig reaction, 10 Morita–Baylis–Hillman (MBH) strategy 11 and Heck-type reaction 12 (Scheme 1a). In 2020, the Tu group developed two novel protocols for synthesizing stereodefined ( Z )-spiroindenes, involving the functionalization of 1,5-enynes with ethyl difluoroiodoacetate and arylsulfonyl hydrazide, respectively.…”