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The first total synthesis of (-)-graminin A is described. Key features of our synthetic approach involve a palladium-catalyzed asymmetric cyclization carbonylation of prochiral propargylic acetate, conversion of the orthoester product into methyl 4-oxo-3-furancarboxylate, and copper complex-mediated aldol condensation of (+)-gregatin B bearing a diene moiety. A new synthesis of (+)-gregatin B and the first synthesis of (-)-graminin A were achieved.

The first example of an asymmetric cyclization-dimerization of (ortho-alkynyl phenyl) (methoxymethyl) sulfides with a palladium(II) bisoxazoline (box) catalyst has been developed. The box ligand enhances the alkynophilicity of benzothienyl palladium(II) intermediate A and thus promotes coordination of the second alkyne substrate, leading to the dimerization. The characteristic properties of the box ligand were supported by density functional theory (DFT) calculations of the intermediate. Axially chiral bibenzothiophenes were obtained in good yields with good enantioselectivities.

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.

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.

The cyclization-carbonylation of alkynyl hydrazones (I) proceeds readily in the presence of palladous trifluoroacetate in DMSO leading to pyrazole-4-carboxylates (IV) in good to high 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.

An asymmetric cyclative acetoxylation of alkenyl alcohols (I) in the presence of a chiral iPr-SPRIX ligand affords optically active 3-acetyloxy-tetrahydrofurans (III).

Palladium and CO: Carbonylation of 1 with [Pd(tfa)2(±)-L1] (tfa = trifluoroacetate) affords the spirofuranone 2 with inversion of the stereochemistry at C17 in 96 % yield. C17-epi-1 also gave the same product 2 with retention of the stereochemistry at C17. Labelling studies show that (13)CO was incorporated into the C5' position of the furanone ring. The first asymmetric version of this new reaction was achieved.

Palladium and CO: Carbonylation of 1 with [Pd(tfa)2(±)-L1] (tfa = trifluoroacetate) affords the spirofuranone 2 with inversion of the stereochemistry at C17 in 96 % yield. C17-epi-1 also gave the same product 2 with retention of the stereochemistry at C17. Labelling studies show that (13)CO was incorporated into the C5' position of the furanone ring. The first asymmetric version of this new reaction was achieved.

Novel enantioselective catalysis involving a Pd(II)-Pd(IV) cycle was developed by utilizing a SPRIX ligand. Treatment of alkenyl alcohols with a catalytic amount of Pd-SPRIX and TfOH in the presence of PhI(OAc)2 gave optically active 3-oxy-tetrahydrofuran derivatives in good yields.