Organic-base-catalyzed synthesis of phthalides via highly regioselective intramolecular cyclization reaction

The organic-base-catalyzed 5-exo intramolecular cyclization reaction of o-alkynylbenzoic acid produces the corresponding phthalide regioselectively in good to excellent yields. The method provides a practical access to the phthalides, an important class of biologically active molecules.     

One-pot synthesis of trifluoromethylated phthalans via intramolecular cyclization from 2-alkynylbenzaldehydes

An efficient tandem addition/cyclization procedure for the synthesis of trifluoromethylated phthalans under mild conditions was developed. This procedure involves tetrabutylammonium fluoride (TBAF)-promoted addition of Ruppert–Prakash reagent (TMSCF₃) to 2-alkynylbenzaldehyde to give 2-alkynylbenzylicalcohols, which would then undergo base-catalyzed selective 5-exo-dig cyclization to furnish the corresponding products.     

One-pot synthesis of triazole-fused isoindoles from o-alkynylbenzaldehydes and trimethylsilyl azide

An efficient one-pot synthesis of 1,2,3-triazole-fused isoindoles from o-alkynylbenzaldehydes and trimethylsilyl azide (TMSN₃) is reported. The reaction proceeds through the formation of a diazide intermediate and a subsequent intramolecular azide-alkyne cycloaddition, providing a novel access to a variety of 8-azido-8H-[1,2,3]triazolo[5,1-a]isoindoles in high yields.     

One-pot synthesis of ortho-hydroxycinnamate esters

Phenols are converted to salicylaldehydes with paraformaldehyde, MgCl₂-Et₃N in THF, and subsequent treatment with methyl (triphenylphosphoranylidene)acetate gave the corresponding methyl ortho-hydroxycinnamate derivatives. The sequence is conveniently carried out as a one-pot procedure.     

Palladium-catalyzed synthesis of dibenzophosphole oxides via intramolecular dehydrogenative cyclization

Dibenzophosphole oxides were obtained from secondary hydrophosphine oxides with a biphenyl group by dehydrogenation via phosphine-hydrogen and carbon-hydrogen bond cleavage in the presence of a catalytic amount of palladium(II) acetate, Pd(OAc)(2). By using this reaction, a ladder-type dibenzophosphole oxide could also be synthesized by double intramolecular dehydrogenative cyclization.     

Enantioselective synthesis of P-stereogenic benzophospholanes via palladium-catalyzed intramolecular cyclization

Enantioselective or diastereoselective intramolecular cyclization of functionalized secondary phosphines or their borane adducts catalyzed by chiral Pd(diphosphine) complexes gave P-stereogenic benzophospholanes in up to 70% ee. These results provide a new method for the synthesis of chiral phospholanes, which are valuable ligands in asymmetric catalysis. [reaction: see text]     

One-pot access to 2-naphthols and benzofurans via the aerobic Wacker-type oxidation/intramolecular aldol cyclization

An aerobic Wacker-type oxidation/intramolecular aldol cyclization synthetic route toward two oxygenated 2-naphthols 3 and benzofurans 4 starting with skeleton 2 with good yields is described. The route has been carried by the one-pot transformation of the regioselective PdCl₂/CuCl₂-mediated Wacker oxidative cyclization of skeleton 2 with molecular oxygen under the alkaline methanolic condition. Skeleton 2 was prepared from skeleton 1 in moderate total yields via the known protocol.     

The synthesis of 1,2-diarylindenes via DDQ-mediated dehydrogenative intramolecular cyclization

A direct DDQ-mediated dehydrogenative intramolecular cyclization of (Z)-1,2,3-triaryl substituted propylenes promoted by Cu(OAc)₂ was developed, providing 1,2-diarylindene derivatives in moderate to good yields (up to 92%) under mild conditions. This protocol provides a straightforward access to 1,2-diarylindenes via DDQ-mediated benzylic/allylic sp³ C–H bond activation.     

A regioselective synthesis of 3-benzazepinones via intramolecular hydroamidation of acetylenes

Synthesis of 3-benzazepinones by palladium-catalyzed intramolecular addition of amides to alkynes is achieved. Phenyl acetylenes substituted in the ortho-position with tethered amide functionality were prepared in a few steps from readily available starting materials. It was found that 5% Pd(OAc)₂(PPh₃)₂ and KOH most effectively promoted cyclization. When the tethered group is an acetamide and an alkyl substituent is on the acetylene unit, regioselective 3-benzazepinone synthesis could be achieved in good yields.     

One-pot regioselective synthesis of dihydronaphthofurans and dibenzofurans

A regioselective approach for the synthesis of substituted naphthofurans and dibenzofurans has been demonstrated through a ring transformation reaction of suitably functionalized 2H-pyran-2-ones by reaction with 6,7-dihydro-5H-benzofuran-4-one and 7-methoxybenzofuran-3-one, respectively, in high yields. The novelty of the procedure lies in the creation of an aromatic ring transformed by 2H-pyran-2-one involving the -COCH₂- moiety of a cyclic ketone.     

Chemical synthesis of a cyclotide via intramolecular cyclization of peptide O-esters

Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications.Here,we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters.This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone,the head-to-tail cyclization of the cyclotide backbone by native chemical ligation,and the oxidative refolding to yield the natural knot protein.The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.     

Construction of novel spiroisoxazolines via intramolecular cyclization/methylation

Improved yields for the syntheses of a variety of spiroisoxazolines were achieved through intramolecular cyclization/methylation reactions of functionalized 5,5-disubstituted isoxazolines in one reaction vessel. Aromatic ring containing nitrile oxides and disubstituted geminal alkenes reacted in a 1,3-dipolar fashion to afford the corresponding 5,5-isoxazoline. A comparison of the relative location of the nucleophile and electrophile on the isoxazoline and two different ester functional groups was performed in order to determine the best isoxazoline system for the intramolecular cyclization/methylation reaction.     

Domino allylation and cyclization of ortho-alkynylbenzaldehydes with allyltrimethylsilane catalyzed by Pd(II)-Cu(II) bimetallic systems

The reaction of ortho-alkynylated benzaldehydes 1 with allyltrimethylsilane under the Pd(OAc)₂-CuCl₂ catalyst system gave the isochromene derivatives 2 together with the chlorinated products 3. When the reaction was conducted in the presence of half equiv of H₂O, the formation of 3 was suppressed and 2 was obtained in good to high yields. When the reaction of 1a was carried out with trimethylsilylcyanide instead of allylsilane, the cyano group-substituted isochromene 9 was obtained in 94% yield.     

Efficient synthesis of the 3-benzazepine framework via intramolecular Heck reductive cyclization

A microwave-assisted protocol based on reductive Heck reaction was developed for regio- and stereoselective construction of the 3-benzazepine core.     

Silver catalyzed intramolecular cyclization for synthesis of 3-alkylideneoxindoles via C-H functionalization

A novel protocol for the preparation of various 3-alkylideneoxindoles via a silver-catalyzed aromatic C-H functionalization has been developed. The process is simple, environmentally conscious, and avoids the use of abundant bases, oxidants, or other additives.     

One-pot synthesis of isoquinoline and related compounds via Cu-mediated tandem cross-coupling and cyclization

One-pot synthetic strategy has been developed to access isoquinolines and its analogs via Cu-mediated tandem cross-coupling and cyclization in good yields under mild reaction conditions. A mixture of suitably substituted α-bromoaldehyde, terminal alkyne, and aq NH₃ in CuI/1,10-phenanathroline catalytic system afforded the 3-substituted isoquinoline regio-selectively in good to excellent yields.     

A facile synthesis of indolo[3,2,1-jk]carbazoles via palladium-catalyzed intramolecular cyclization

A new efficient synthesis of indolo[3,2,1-jk]carbazoles by the palladium-catalyzed cyclization of N-(2-bromoaryl)carbazoles is described. The reaction involves intramolecular C-C bond formation, coupled with the cleavage of a C-X bond and a C-H bond on carbazole ring. Substitutions on N-aryl core with either electron-donating or electron-withdrawing groups are introduced, and different reaction factors for cyclization are evaluated.     

Total synthesis of diptoindonesin G via a highly efficient domino cyclodehydration/intramolecular Friedel-Crafts acylation/regioselective demethylation sequence

A highly efficient total synthesis of diptoindonesin G is described employing a domino dehydrative cyclization/intramolecular Friedel-Crafts acylation/regioselective demethylation reaction of aryloxyketone 7 by the action of BCl(3) wherein the tetracyclic 6H-anthra[1,9-bc]furan-6-one skeleton was constructed via the 3-arylbenzofuran in a one-pot manner. This is the first example of the strategic combination of these three reactions in a cascade fashion. The routes presented here allow for direct access to diptoindonesin G and its analogues.     

BF3-Et2O mediated biogenetic type synthesis of chromanochalcones from prenylated chalcones via a regioselective cyclization reaction

In continuation of our program on synthetic chalcones, we have developed a simple and convenient method for the synthesis of chromanochalcones from prenylated chalcones in high yields by regioselective cyclization using BF₃-Et₂O.