•Regioselective elimination of a vicinal bis-triflate having an adjacent ether oxygen functional group has been developed.•An unusual combination of n-BuLi/dichloromethane led to the high selectivity of elimination reaction.•The key involved the electron-withdrawing inductive effect of an adjacent ether oxygen functional group.Regioselective elimination of a vicinal bis-triflate having an adjacent ether oxygen functional group has been developed. Considered in the context of our studies of the regioselective elimination of vicinal dibromide, the key to the mechanism involves the electron-withdrawing inductive effect of the neighboring oxygen functional group. Aliphatic vinyl triflate was shown to be effective in Suzuki–Miyaura cross coupling compared with corresponding aliphatic vinyl bromide.Download high-res image (71KB)Download full-size image

•Total synthesis of a quinolinone alkaloid haplacutine C is achieved.•The keys are the intramolecular aldol condensation and the Stille coupling.•The 4-O-protected-quinolines are utilized as the synthetic equivalents of 4-quinolinone skeletons.A total synthesis of haplacutine C has been achieved. The synthetic key features were the intramolecular aldol condensation for construction of the 4-quinolinone skeleton and the Stille coupling for elongation of the dienol side chain. In addition, the 4-O-protected-quinolines were also utilized as the synthetic equivalents of 4-quinolinone at the stage of side chain transformation.

Brønsted acid-promoted intramolecular hydroarylation of alkynylbenzenes carrying an arylalkyl group at the ortho-position leads to alkylidenedibenzo[a,d]cycloheptenes, -octenes and -nonenes in up to quantitative yield with complete regioselectivity. The scope and limitation of this reaction and application to the synthesis of tricyclic antidepressants are described.

We describe the stereoselective synthesis of polyring-fused heterocyclic compounds based on diene-transmissive hetero-Diels–Alder reactions utilizing β,γ-unsaturated α-keto esters. This protocol involves the initial endo- or exo-selective Diels–Alder (DA) reactions with electron-rich dienophiles, methylenation of the ester carbonyl groups with the Tebbe reagent, and a stereoselective second DA reaction with electron-deficient dienophiles. The use of enantioselective DA reactions in the initial reaction enables access to chiral polyring-fused heterocyclic compounds with multiple chiral centres.

Cross-conjugated 1-azatrienes ([3]-1-azadendralenes) bearing a sulfonyl group on the nitrogen atom were converted to various polyhydroquinolines with multiple stereocentres via a diene-transmissive hetero-Diels–Alder (DA) reaction consisting of an inverse electron-demand aza-DA reaction with electron-rich dienophiles followed by a stereoselective DA reaction with electron-deficient dienophiles.

The first total synthesis of aplysinoplide B has been achieved. The synthetic highlight of our approach includes sp2–sp3 Suzuki–Miyaura cross coupling of a vinyl bromide with an alkyl 9-BBN derivative. The vinyl bromide was efficiently synthesized from the disubstituted Z-alkene utilizing a one-pot regioselective bromination. Through the synthetic studies, the absolute stereochemistry at the C4 position of naturally occurring aplysinoplide B was established as an R configuration.

The first total synthesis of (−)-5,6-seco-germacrane lactone has been achieved. The synthetic highlight of our approach includes sp2–sp3 Suzuki–Miyaura cross coupling of a vinyl bromide and an alkyl 9-BBN derivative. The vinyl bromide was easily prepared from the chiral lactonic building block using a one-pot regioselective bromination. The asymmetric carbon center of the alkyl boron compound was formed using the zirconium-catalyzed carbomagnesation of 2,5-dihydrofuran.

Acid-responsive fluorescent compounds were prepared by introducing a nitrophenyl group to L-shaped pentacycles with a pyrrolo[1,2-a][1,8]naphthylidine backbone. These compounds show almost no fluorescence under neutral conditions, but emit green to orange fluorescence upon addition of trifluoroacetic acid. Acid titration experiments and NMR spectroscopy, plus DFT calculations, show that formation of a pyridinium cation species is responsible for the appearance of fluorescence.

A new approach towards the synthesis of indole derivatives via triflic acid-promoted cycloisomerization with rearrangement of 2-(alkyn-1-yl)phenyl isothiocyanates and 2-(alkyn-1-yl)phenyl isocyanates has been achieved. By this methodology, structurally diverse types of indole derivatives such as thieno- and furo-indoles, spiro-indolethiones, spiro-oxindoles, and 3-alkylidene-oxindoles were synthesized.

Stereoselective synthesis of hexahydroquinazolin-2(1H)-ones has been achieved through the application of the diene-transmissive hetero-Diels–Alder methodology to 2-vinyl-1-aza-1,3-butadienes. The cross-conjugated 1-azatriene underwent an initial hetero-Diels–Alder reaction on the 1-aza-1,3-butadiene system with tosyl isocyanate to afford the [4 + 2] mono-cycloadduct pyrimidinone. The second Diels–Alder reaction on the electron-rich 1-amino-1,3-diene unit of the mono-cycloadduct with dienophiles provided hexahydroquinazolin-2(1H)-ones with high stereoselectivity.

Cycloisomerization of N-[2-(2-alkyn-1-yl)phenyl]carbodiimides 1 catalysed by Rh(dppp)2Cl under heating conditions afforded 3-(cis-alken-1-yl)-2-(substituted amino)quinolines in up to 87% yield with high cis-selectivity. Scope, limitations, a proposed mechanism for these reactions, and a one-pot synthesis of their trans-isomers from 1 with iodine-promoted olefin isomerization are described.

L-shaped π-extended penta-, hexa-, and heptacycles with a pyrrolo[1,2-a][1,8]naphthyridine junction were prepared from N,N′-bis[2-(2-alkyn-1-yl)phenyl]carbodiimides or their naphthyl analogs via Rh(I)-catalyzed intramolecular [2+2+2] cycloaddition and dehydrogenative aromatization. These L-shaped compounds emit sky-blue, yellow-green, or golden-orange fluorescence, with high quantum yields.

In this study, we achieved the first total synthesis of (+)-heteroplexisolide E. The synthetic highlights of our approach include a one-pot regioselective methylation method and the transformation of a β-methallyl alcohol moiety to a prenyl group using palladium-catalyzed hydrogenolysis.

An efficient one-pot method for bromination−elimination of allyl alcohol derivatives and sequential Sonogashira coupling has been developed. A highlight of the method is chemoselective DBU-promoted elimination of vicinal dibromoalkanes having an adjacent O-functional group.

A new straightforward synthetic method for 2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-2-ones via a [RhCl(CO)2]2–dppp catalyzed Pauson–Khand-type reaction of N-[2-(2-alkyn-1-yl)phenyl]carbodiimides is reported.

The first examples of CS induced Pauson–Khand type reactions are described; 2-alkynylphenyl isothiocyanates were converted to 3-substituted-2H-thieno[2,3-b]indol-2-ones in the presence of a stoichiometric amount of Mo(CO)6 or Co2(CO)8, or a catalytic amount of Rh catalyst under an atmospheric pressure of carbon monoxide.

The first examples of CS induced Pauson–Khand type reactions are described; 2-alkynylphenyl isothiocyanates were converted to 3-substituted-2H-thieno[2,3-b]indol-2-ones in the presence of a stoichiometric amount of Mo(CO)6 or Co2(CO)8, or a catalytic amount of Rh catalyst under an atmospheric pressure of carbon monoxide.

L-shaped π-extended penta-, hexa-, and heptacycles with a pyrrolo[1,2-a][1,8]naphthyridine junction were prepared from N,N′-bis[2-(2-alkyn-1-yl)phenyl]carbodiimides or their naphthyl analogs via Rh(I)-catalyzed intramolecular [2+2+2] cycloaddition and dehydrogenative aromatization. These L-shaped compounds emit sky-blue, yellow-green, or golden-orange fluorescence, with high quantum yields.

We describe the stereoselective synthesis of polyring-fused heterocyclic compounds based on diene-transmissive hetero-Diels–Alder reactions utilizing β,γ-unsaturated α-keto esters. This protocol involves the initial endo- or exo-selective Diels–Alder (DA) reactions with electron-rich dienophiles, methylenation of the ester carbonyl groups with the Tebbe reagent, and a stereoselective second DA reaction with electron-deficient dienophiles. The use of enantioselective DA reactions in the initial reaction enables access to chiral polyring-fused heterocyclic compounds with multiple chiral centres.

A new straightforward synthetic method for 2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-2-ones via a [RhCl(CO)2]2–dppp catalyzed Pauson–Khand-type reaction of N-[2-(2-alkyn-1-yl)phenyl]carbodiimides is reported.

Brønsted acid-promoted intramolecular hydroarylation of alkynylbenzenes carrying an arylalkyl group at the ortho-position leads to alkylidenedibenzo[a,d]cycloheptenes, -octenes and -nonenes in up to quantitative yield with complete regioselectivity. The scope and limitation of this reaction and application to the synthesis of tricyclic antidepressants are described.

Stereoselective synthesis of hexahydroquinazolin-2(1H)-ones has been achieved through the application of the diene-transmissive hetero-Diels–Alder methodology to 2-vinyl-1-aza-1,3-butadienes. The cross-conjugated 1-azatriene underwent an initial hetero-Diels–Alder reaction on the 1-aza-1,3-butadiene system with tosyl isocyanate to afford the [4 + 2] mono-cycloadduct pyrimidinone. The second Diels–Alder reaction on the electron-rich 1-amino-1,3-diene unit of the mono-cycloadduct with dienophiles provided hexahydroquinazolin-2(1H)-ones with high stereoselectivity.

A new approach towards the synthesis of indole derivatives via triflic acid-promoted cycloisomerization with rearrangement of 2-(alkyn-1-yl)phenyl isothiocyanates and 2-(alkyn-1-yl)phenyl isocyanates has been achieved. By this methodology, structurally diverse types of indole derivatives such as thieno- and furo-indoles, spiro-indolethiones, spiro-oxindoles, and 3-alkylidene-oxindoles were synthesized.