A formal synthesis of tirandamycin B is described. The key intermediate is synthesized by Marshall allenyl zinc method, litiofuran coupling, and Achmatowicz reaction to construct the bicyclic core of tirandamycin B.Download high-res image (88KB)Download full-size image

AbstractThe hydration of alkynes catalyzed by palladium(II) bis(oxazoline) complexes is described. The corresponding ketones were obtained in good yields and no special additives were required.

Allylative cyclization of (o-alkynylphenyl) (methoxymethyl) sulfides, o-alkynylanilines and o-alkynylphenols catalyzed by π-allyl palladium species generated from simple allylic alcohols is described. 3-Allylbenzo[b]thiophenes, 3-allylindoles and 3-allylbenzofurans were obtained in good yields using aqueous media under neutral conditions.

A simple change of ligand and solvent allows controlled, effective switching between cyclization–carbonylation and cyclization–carbonylation–cyclization-coupling (CCC-coupling) reactions of 2-alkynylanilines catalyzed by palladium(II). The use of a [Pd(tfa)2(box)] catalyst in iPrOH afforded symmetrical ketones bearing two indoles in good yields; replacing the catalyst and solvent with Pd(tfa)2 and DMSO–MeOH led to the formation of methyl 1-benzyl-1H-indole-3-carboxylates in good yields.

Cyclization–carbonylation of α,β-alkynic hydrazones and (o-alkynylphenyl) (methoxymethyl) sulfides with Pd(tfa)2 in DMSO/MeOH afforded methyl pyrazole-4-carboxylates and benzo[b]thiophene-3-carboxylates, respectively, in good yields. A simple change of the ligand (solvent) allowed controlled, effective switching between cyclization–carbonylation–cyclization-coupling (CCC-coupling) reactions and cyclization–carbonylation reactions.

A cyclization–carbonylation–cyclization coupling reaction (CCC-coupling reaction) of (o-alkynylphenyl) (methoxymethyl) sulfides, catalyzed by (box)PdII complexes, afforded symmetrical ketones bearing two benzo[b]thiophene groups in good to excellent yields. This method is applicable to a broad range of substrates.

The first total synthesis of (+)-gregatin E and a new total synthesis of (+)-gregatin B are described. Key features of our synthetic approach involve a palladium-catalyzed cyclization–methoxycarbonylation of optically active propargylic acetate and a Suzuki–Miyaura coupling or CuTC-mediated coupling reaction. The absolute configuration of (+)-gregatin E (5R,5′S) is proposed.

A cyclization–carbonylation–cyclization coupling reaction (CCC-coupling reaction) of α,β-alkynic hydrazones, catalyzed by (box)PdII complexes, afforded symmetrical ketones bearing two pyrazole groups in good to excellent yields. This method is applicable to a broad range of substrates.

Cyclization–carbonylation–cyclization coupling reaction (CCC-coupling reaction) of γ-propynyl-1,3-diketones catalyzed by (box)PdII complexes afforded symmetrical ketones bearing two oxabicyclic groups in moderate to excellent yields.

Palladium(II) catalyzed carbonylation of 1-ethynyl-1-propargyl acetate 1 is described; in the absence of the bisoxazoline (box) ligand, the second triple bond did not react, affording cyclic orthoesters 3 and 4. The use of meso-Phbox-Pd(II) strikingly changed the course of the reaction, yielding bicyclic lactone 2 by tandem carbonylative cyclization as a result of insertion of the second triple bond.

Cyclization–carbonylation–cyclization coupling reaction (CCC-coupling reaction) of γ-propynyl-1,3-diketones catalyzed by (box)PdII complexes afforded symmetrical ketones bearing two oxabicyclic groups in moderate to excellent yields.

A cyclization–carbonylation–cyclization coupling reaction (CCC-coupling reaction) of α,β-alkynic hydrazones, catalyzed by (box)PdII complexes, afforded symmetrical ketones bearing two pyrazole groups in good to excellent yields. This method is applicable to a broad range of substrates.

A cyclization–carbonylation–cyclization coupling reaction (CCC-coupling reaction) of (o-alkynylphenyl) (methoxymethyl) sulfides, catalyzed by (box)PdII complexes, afforded symmetrical ketones bearing two benzo[b]thiophene groups in good to excellent yields. This method is applicable to a broad range of substrates.

A simple change of ligand and solvent allows controlled, effective switching between cyclization–carbonylation and cyclization–carbonylation–cyclization-coupling (CCC-coupling) reactions of 2-alkynylanilines catalyzed by palladium(II). The use of a [Pd(tfa)2(box)] catalyst in iPrOH afforded symmetrical ketones bearing two indoles in good yields; replacing the catalyst and solvent with Pd(tfa)2 and DMSO–MeOH led to the formation of methyl 1-benzyl-1H-indole-3-carboxylates in good yields.

Palladium(II) catalyzed carbonylation of 1-ethynyl-1-propargyl acetate 1 is described; in the absence of the bisoxazoline (box) ligand, the second triple bond did not react, affording cyclic orthoesters 3 and 4. The use of meso-Phbox-Pd(II) strikingly changed the course of the reaction, yielding bicyclic lactone 2 by tandem carbonylative cyclization as a result of insertion of the second triple bond.

Cyclization–carbonylation of α,β-alkynic hydrazones and (o-alkynylphenyl) (methoxymethyl) sulfides with Pd(tfa)2 in DMSO/MeOH afforded methyl pyrazole-4-carboxylates and benzo[b]thiophene-3-carboxylates, respectively, in good yields. A simple change of the ligand (solvent) allowed controlled, effective switching between cyclization–carbonylation–cyclization-coupling (CCC-coupling) reactions and cyclization–carbonylation reactions.