Catalytic Synthesis of Saturated Oxygen Heterocycles by Hydrofunctionalization of Unactivated Olefins: Unprotected and Protected Strategies.

A mild, general, and functional group tolerant intramolecular hydroalkoxylation and hydroacyloxylation of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent is described. This reaction was carried out at room temperature and afforded five- and six-membered oxygen heterocyclic compounds, such as cyclic ethers and lactones. The Co complex was optimized for previously rare medium ring formation by hydrofunctionalization of unactivated olefins. The powerful Co catalyst system also enables the deprotective hydroalkoxylation of O-protected alkenyl alcohol and hydroacyloxylation of alkenyl ester to afford cyclic ethers and lactones directly. The substrate scope and mechanistic proof of deprotection were investigated. The experimental evidence supports the concerted transition state of the bond-forming step involving a cationic Co complex.

Markovnikov-Selective Addition of Fluorous Solvents to Unactivated Olefins Using a Co Catalyst.

We developed an addition reaction of fluorous solvents to olefins using salen-cobalt (Co) complex, N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate, and 1,1,3,3-tetramethyldisiloxane. This reaction condition was found to activate olefins, which enabled them to be attacked by 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), both of which are electronically weak nucleophiles.

Catalytic hydroamination of unactivated olefins using a Co catalyst for complex molecule synthesis.

Functional group tolerance is one of the important requirements for chemical reactions, especially for the synthesis of complex molecules. Herein, we report a mild, general, and functional group tolerant intramolecular hydroamination of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent. This method, which was carried out at room temperature (or 0 °C), afforded three-, five-, six-, and seven-membered ring nitrogen-containing heterocyclic compounds and was compatible with diverse functional groups.

Hydroalkoxylation of unactivated olefins with carbon radicals and carbocation species as key intermediates.

A unique Markovnikov hydroalkoxylation of unactivated olefins with a cobalt complex, silane, and N-fluoropyridinium salt is reported. Further optimization of reaction conditions yielded high functional group tolerance and versatility of alcoholic solvent employed, including methanol, i-propanol, and t-butanol. Use of trifluorotoluene as a solvent made the use of alcohol in stoichiometric amount possible. Mechanistic insight into this novel catalytic system is also discussed. Experimental results suggest that catalysis involves both carbon radical and carbocation intermediates.

Total synthesis of optically active lycopladine A by utilizing diastereoselective protection of carbonyl group in a 1,3-cyclohexanedione derivative.

We successfully synthesized two enantiomers of bicyclic enones, (7R,7aR)- and (7S,7aS)-9, from the hemiacetal 2a, which we first synthesized from the symmetrical diketone 1a via diastereoselective carbon-oxygen bond formation between one of the carbonyl groups and the chiral alcohol on the C2 side chain in a 2,2-disubstituted 1,3-cycloalkanedione derivative. We also report the total synthesis of natural (+)-lycopladine A [(+)-6] from (7R,7aR)-9 and the formal synthesis of unnatural (-)-lycopladine A [(-)-6] from (7S,7aS)-9.

Palladium-catalyzed intramolecular amidation of C(sp2)-H bonds: synthesis of 4-aryl-2-quinolinones.

A catalytic synthetic approach for the synthesis of 2-quinolinone compounds through a Pd-catalyzed C(sp(2))-H functionalization/intramolecular amidation sequence is described. The cyclization process efficiently proceeds in the presence of a catalytic amount of PdCl(2) and Cu(OAc)(2) under an O(2) atmosphere, providing practical access to a range of variously substituted 4-aryl-2-quinolinones.

Development of diastereoselective birch reduction-alkylation reactions of bi- and tricyclic beta-alkoxy-alpha,beta-unsaturated ketones.

Diastereoselective Birch reduction-alkylation reactions of bicyclic beta-alkoxy-alpha,beta-unsaturated carbonyl compounds and tricyclic analogues were investigated. Although the relative configuration of the product was altered according to the structure of the starting material, stereoselectivity of the reaction could be accounted for by similar reaction pathways. The product from the tricyclic beta-alkoxy-alpha,beta-unsaturated carbonyl compound corresponded to the trichothecene skeleton.

Palladium-catalysed direct synthesis of benzo[b]thiophenes from thioenols.

The one-pot conversion of thioenols into benzo[b]thiophenes was achieved by using a simple palladium catalyst such as PdCl(2) or PdCl(2)(cod).

Palladium-catalyzed C-H activation/intramolecular amination reaction: a new route to 3-aryl/alkylindazoles.

A method for the catalytic C-H activation of hydrazone compounds followed by intramolecular amination is described. It requires the use of a catalytic amount of Pd(OAc)2 in the presence of Cu(OAc)2 and AgOCOCF3, which efficiently effects the cyclization to afford variously substituted indazoles. The reactions proceed under relatively mild conditions and thus tolerate a variety of functional groups, including alkoxycarbonyl and cyano groups and halogen atoms.

Cyclization reactions of homopropargyl azide derivatives catalyzed by PtCl4 in ethanol solution: synthesis of functionalized pyrrole derivatives.

[Structure: see text] PtCl4-catalyzed cyclization reactions of homopropargyl azide derivatives to pyrrole rings were investigated. Using ethanol as solvent with 2,6-di-tert-butyl-4-methylpyridine as the base was found to be the best set of conditions for effecting this ring-closing reaction. These reaction conditions can be applied to the preparation of functionalized pyrrole derivatives, with no effect on the functional groups.

Regiocontrolled intramolecular cyclizations of carboxylic acids to carbon-carbon triple bonds promoted by acid or base catalyst.

We systematically investigated, for the first time, the relationship between regioselectivity and acid/base effects in the cyclization reactions between carboxylic acids and carbon-carbon triple bonds. We found novel acid- and base-promoted cyclizations to selectively give isocoumarin or pyran-2(2H)-one and phthalide or furan-2(5H)-one skeletons, respectively, and established a catalytic version of regioselective heterocyclic ring synthesis. Density functional theory calculations and application to a short route to thunberginol A were also described. [reaction: see text].

Co-Catalyzed Hydroarylation of Unactivated Olefins.

A mild, general, scalable, and functional group tolerant intramolecular hydroarylation of unactivated olefins using a Co(salen) complex, a N-fluoropyridinium salt, and a disiloxane reagent was reported. This method, which was carried out at room temperature, afforded six-membered benzocyclic compounds from mono-, 1,1- or trans-1,2-di, and trisubstituted olefins.

New synthetic method for indole-2-carboxylate and its application to the total synthesis of duocarmycin SA.

The sequential coupling and cyclization reactions between aryl halides and methyl propiolate were investigated. The electron-withdrawing groups on the aromatic ring are essential for producing the methyl indole-2-carboxylate derivatives. On the other hand, the presence of an extra methyl propiolate and Pd(PPh3)4 were required to provide an efficient catalytic system for the cyclization reactions. This reaction was used for the total synthesis of duocarmycin SA.

Cobalt-catalyzed hydrofluorination of unactivated olefins: a radical approach of fluorine transfer.

Catalytic hydrofluorination of olefins using a cobalt catalyst was developed. The exclusive Markovnikov selectivity, functional group tolerance, and scalability of this reaction make it an attractive protocol for the hydrofluorination of olefins. A preliminary mechanistic experiment showed the involvement of a radical intermediate.

Tandem-type Pd(II)-catalyzed oxidative Heck reaction/intramolecular C-H amidation sequence: a novel route to 4-aryl-2-quinolinones.

A novel catalytic method for synthesizing 4-aryl-2-quinolinones is reported. The process involves two mechanistically independent, sequential Pd(II)-catalyzed reactions--the oxidative Heck reaction and the intramolecular C-H amidation--both of which smoothly proceed in the presence of a single catalytic system in a one-pot manner.

Use of dimethyl carbonate as a solvent greatly enhances the biaryl coupling of aryl iodides and organoboron reagents without adding any transition metal catalysts.

The coupling reaction of aryl iodides with arylboronic acids to give biaryl compounds can be efficiently performed without adding a transition metal catalyst. The key to success is the use of dimethyl carbonate as a solvent. This finding provides a new strategy for constructing a biaryl linkage.

Palladium-catalyzed synthesis of 2-substituted benzothiazoles via a C-H functionalization/intramolecular C-S bond formation process.

Catalytic synthesis of 2-substituted benzothiazoles from thiobenzanilides was achieved in the presence of a palladium catalyst through C-H functionalization/C-S bond formation. This method features the use of a novel catalytic system consisting of 10 mol % of Pd(II), 50 mol % of Cu(I), and 2 equiv of Bu4NBr that produced variously substituted benzothiazoles in high yields with good functional group tolerance.

The new method for introduction of an allyl group into the angular position of 2-(TBS-oxymethyl)-2,3,4,6,7,8-hexahydro-1-benzopyran-5-one and its application to chiral Wieland-Miescher type compound synthesis.

The stereoselective introduction of an allyl group into the angular position of 2-(TBS-oxymethyl)-2,3,4,6,7,8-hexahydro-1-benzopyran-5-one was accomplished using Birch reduction and an enolate trapping reaction. It was determined that the allyl group was introduced via an unexpected conformation-flipped from the initially formed one. Two diastereomeric Wieland-Miescher type compounds, having the allyl group at the angular position, were synthesized as optically pure forms.