Synthesis of β-methoxyacrylate natural products based on box-Pd(II)-catalyzed intermolecular methoxycarbonylation of alkynoles.

Bis(oxazoline)-palladium(II) catalyzed carbonylation of homopropargyl alcohols afforded acyclic methoxyacrylate 2 and 6-membered lactone 3a-k in good combined yield. In the case of propargyl alcohols, 5-membered lactones 3p, 3q, 16 were obtained in moderate yields. The one-pot synthesis of kawa lactones 3a, 3r, 3s and formal synthesis of dihydroxycystothiazole A and dihydroxycystothiazole C are presented.

Intermolecular methoxycarbonylation of terminal alkynes catalyzed by palladium(II) bis(oxazoline) complexes.

Boxing clever: Direct conversion of a terminal alkyne group into a beta-methoxyacrylate is realized with the aid of the bis(oxazoline) ligand (box). Acetyl and ketal protecting groups, free hydroxy groups, and acid-sensitive glycosidic bonds are not affected under the reaction conditions. The one-pot synthesis of (+/-)-dihydrokawain from the homopropargyl alcohol is also achieved.

Conversion of optically active hydrindanone to (+)-bakkenolide-A.

A total synthesis of (+)-bakkenolide-A was carried out via the key intermediate 4, which was prepared based on an asymmetric cyclization-carbonylation reaction established in our laboratory. Diastereoselective construction of the spirolactone moiety was achieved using Mitsuhashi's protocol as a key step.

meso-Phbox-Pd(II) catalyzed tandem carbonylative cyclization of 1-ethynyl-1-propargyl acetate.

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