Efficient synthesis of highly functionalized indole and phenol containing 3,3′-disubstituted oxindoles and chromene fused spirooxindoles
3-Alkynyl-3-OBoc oxindoles underwent Cu(II) mediated Friedel-Crafts alkylation with indoles and phenols to yield of structurally diverse 3-alkynyl-3-indole/phenol-oxindole derivatives. The synthetic application of alkylated phenol derivatives were further demonstrated to biologically important new class of chromene fused spirooxindoles through intramolecular metal-free iodocyclization under mild reaction conditions with broad substrate scope in very good yields.
Recent advances in aerobic oxidation with ruthenium catalysts
Oxidation reactions are significant transformations used extensively in chemical production. Use of molecular oxygen as an oxidant is certainly environmental friendly and adds to the greenness of the process. A number of metal catalysts have been developed for aerobic oxidation. This digest summarizes the recent advances in aerobic oxidation reactions using ruthenium catalysts for various transformations such as C–H activation/cyclization, alkyne/alkene oxidation, and oxidation of alcohols and amines.
Enantioselective Synthesis of 3-Acetyl Coumarin Substituted 3-Hydroxy Oxindoles and Pyranocoumarin Fused Spirooxindoles
Enantioselective construction of bioinspired coumarin and oxindole hybrid structures always enduring challenges in organic chemistry due to the generation of asymmetric quaternary/spiro center at the C3 position of oxindole. Herein, we demonstrated a facile enantioselective synthesis of highly functionalized 3,3’-disubstituted oxindole derivatives containing 3-acetyl coumarins and pyranocoumarin fused spirooxindoles using L-proline derived bifunctional thiourea organocatalyst through Aldol reaction and Michael addition/cyclization. The L-proline derived thiourea catalyst well performed with broad substrate scope to produce desired products in very good yields (up to 95 %) and excellent enantioselectivities (up to 99 % ee).
Enantioselective Synthesis of Dihydrospiro[indoline-3,4′-pyrano[2,3-c]pyrazole] Derivatives via Michael/Hemiketalization Reaction
A new bifunctional squaramide organocatalyst derived from l-proline mediated the first enantioselective synthesis of dihydrospiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives in excellent enantioselectivity by reacting pyrazolones with isatylidine β,γ-unsaturated α-ketoester. This new catalyst outperformed widely used thioureas and squaramides in inducing enantioselectivity.
Assembly of 3-allyl-3-ethynyl-oxindole motifs via palladium(ii)-catalyzed quaternary allylation of 3-ethynyl-3-OBoc-oxindoles
Palladium(ii)-catalyzed C3-allylation of 3-ethynyl-3-OBoc oxindole derivatives was achieved for the first time to access highly functionalized 3-allyl-3-ethynyl substituted oxindole derivatives for a broad range of substrates in very good yields (up to 94%). The synthetic applications of the allylated products were explored by synthesizing five and six membered carbocyclic spirooxindoles in moderate to very good diastereoselectivities.
Palladium catalyzed asymmetric allylation of 3-OBoc-Oxindoles: An efficient synthesis of 3-Allyl-3-hydroxyoxindoles
3-Allyl-3-hydroxyoxindoles were synthesized in very good enantio- (up to 97% ee) and diastereoselectivities (dr up to 7.6:1) with contiguous quaternary and tertiary stereogenic centers by employing tartrate derived bi(oxazoline) in Pd-catalyzed allylation of 3-OBoc-oxindole. Synthetic utility of 3-allyl-3-hydroxyoxindole was demonstrated by synthesizing a highly substituted spiro(oxindole-3,2′-tetrahydrofuran) derivative in good yield and stereoselectivity.
Palladium-catalyzed asymmetric allylic alkylation of 3-amino-2-oxindoles: Synthesis of 3-allyl-3-amino-2-oxindoles
Tartrate derived bi(oxazoline) ligand with palladium (II) species catalyzed asymmetric allylic alkylation reaction to access highly valuable 3-allyl-3-amino-2-oxindoles with vicinal quaternary and tertiary stereocenters in very good yields (up to 91%) and excellent enantioselectivity (up to 98% ee) with moderate to good diastereoselectivity (up to 5:1). The synthetic utility of 3-allyl-3-amino-2-oxindole was further demonstrated to construct spiro(oxindole-3,2′-pyrrolidine) with consecutive one quaternary and three tertiary chiral centers in good stereoselectivity (dr = 8:1 and 80% ee) through metal-free intramolecular iodocyclization reaction.
Enantioselective Synthesis of 3-Amino-3’-carbazole Oxindole Derivatives via Friedel-Crafts Aminoalkylation Reaction
Organocatalytic Friedel-Crafts aminoalkylation reaction is demonstrated in this study for the construction of biologically important hybrid molecular architectures of carbazole containing 3-amino oxindoles using bifunctional cinchonidine derived thiourea organocatalyst. The Friedel-Crafts functionalization of 4-hydroxy carbazole with isatin derived ketimines well performed with a wide range of substrates resulted in excellent yields (up to 95 %) and enantioselectivities (up to 99 % ee) of the desired products. A minimal catalyst loading (0.5 mol%) was utilized at ambient temperatures under mild reaction conditions.
Diastereo- and Enantioselective Synthesis of 2,2-Disubstituted Benzofuran-3-one Bearing Adjacent Quaternary and Tertiary Stereocenters
The first highly diastereo- and enantioselective synthesis of armeniaspirol analogues was achieved using L-proline derived bifunctional squaramide which outperformed commonly used organocatalysts. Excellent yield (up to 99%) with diastereoselectivity (up to 99:1) and enantioselectivity (up to 99%) were obtained for a wide range of substrates.
Stereoselective and Regioselective Assembly of Spirooxindole [2,1-b]furan Motifs through a Tandem Friedel–Crafts Alkylation/5-exo-dig-Cyclization
3-Alkynyl-3-OBoc (Boc = tert-butoxycarbonyl) oxindole derivatives underwent a CuII-mediated stereo- and regioselective Friedel–Crafts alkylation/5-exo-dig-cyclization with 2-naphthols or cyclic 1,3-diketones. This gave spirooxindole [2,1-b]furan motifs in good to excellent yields under ambient conditions, and the process has a wide substrate scope.