Selective Activation of Aromatic Aldehydes Promoted by Dispersion Interactions: Steric and Electronic Factors of a π-Pocket within Cage-Shaped Borates for Molecular Recognition.

Selective bond formations are one of the most important reactions in organic synthesis. In the Lewis acid mediated electrophile reactions of carbonyls, the selective formation of a carbonyl-acid complex plays a critical role in determining selectivity, which is based on the difference in the coordinative interaction between the carbonyl and Lewis acid center. Although this strategy has attained progress in selective bond formations, the discrimination between similarly sized aromatic and aliphatic carbonyls that have no functional anchors to strongly interact with the metal center still remains a challenging issue. Herein, this work focuses on molecular recognition driven by dispersion interactions within some aromatic moieties. A Lewis acid catalyst with a π-space cavity, which is referred to as a π-pocket, as the recognition site for aromatic carbonyls is designed. Cage-shaped borates 1B with various π-pockets demonstrated significant chemoselectivity for aromatic aldehydes 3 b-f over that of aliphatic 3 a in competitive hetero-Diels-Alder reactions. The effectiveness of our catalysts was also evidenced by intramolecular recognition of the aromatic carbonyl within a dicarbonyl substrate. Mechanistic and theoretical studies demonstrated that the selective activation of aromatic substrates was driven by the preorganization step with a larger dispersion interaction, rather than the rate-determining step of the C-C bond formation, and this was likely to contribute to the preferred activation of aromatic substrates over that of aliphatic ones.

Regio- and Stereoselective Allylindation of Alkynes Using InBr3 and Allylic Silanes: Synthesis, Characterization, and Application of 1,4-Dienylindiums toward Skipped Dienes.

Regioselective anti-allylindation of alkynes was achieved using InBr3 and allylic silanes. Various types of alkynes and allylic silanes were applicable to the present allylindation. This sequential process used the generated 1,4-dienylindiums to establish novel synthetic methods for skipped dienes. The 1,4-dienylindiums were characterized by spectral analysis and treated with I2 to stereoselectively give 1-iodo-1,4-dienes. The Pd-catalyzed cross coupling of 1,4-dienylindium with iodobenzene successfully proceeded in a one-pot manner to afford the corresponding 1-aryl-1,4-diene.

Catalytic Annulation of Epoxides with Heterocumulenes by the Indium-Tin System.

In the synthesis of five-membered heterocycles by the annulation of epoxides with heterocumulenes such as carbon dioxide and isocyanates, we developed the indium-tin catalytic system and synthesized various cyclic adducts including novel types products under mild reaction conditions.

Tuning Lewis Acidity by a Transannular pπ -σ* Interaction between Boron and Silicon/Germanium Atoms Supported by a Cage-Shaped Framework.

Cage-shaped borates tethered by heavier Group 14 elements (Si or Ge) were synthesized. These possess an intramolecularly transannular pπ -σ* interaction between the boron center and the tethered Si/Ge atom, which allows the precise tuning of their Lewis acidity. The Lewis acidity was investigated by the ligand-exchange reaction rate and IR measurements with the help of theoretical calculation. The synthesized borates exhibited catalytic activity. This study demonstrated the effectiveness of the direct orbital perturbation of a metal center by space interaction during fine tuning of the Lewis acidity.

C3 -Symmetric Boron Lewis Acid with a Cage-Shape for Chiral Molecular Recognition and Asymmetric Catalysis.

Chiral Lewis acids play an important role in the precise construction of various types of chiral molecules. Here, a cage-shaped borate 2 was designed and synthesized as a chiral Lewis acid that possesses a unique C3 -symmetric structure composed of three homochiral binaphthyl moieties. The highly symmetrical structure of 2 with homochirality was clearly elucidated by X-ray crystallographic analysis. The peculiar chiral environment of 2⋅THF exhibited chiral recognition of some simple amines and a sulfoxide. Moreover, the application of 2⋅THF to hetero-Diels-Alder reactions as a chiral Lewis-acid catalyst afforded the enantioselective products, which were obtained through an entropy-controlled pathway according to the analysis of the relationship between optical yield and reaction temperature. In particular, the robust chiral reaction field of 2⋅THF allowed the first example of an asymmetric hetero-Diels-Alder reaction with a simple diene despite the requirement of high temperature.

Synthesis of Thioethers by InI3-Catalyzed Substitution of Siloxy Group Using Thiosilanes.

The substitution of a siloxy group using thiosilanes smoothly occurred in the presence of InI3 catalyst to yield the corresponding thioethers. InI3 was a specifically effective catalyst in this reaction system, while other typical Lewis acids such as BF3⋅OEt2, AlCl3, and TiCl4 were ineffective. Various silyl ethers such as primary alkyl, secondary alkyl, tertiary alkyl, allylic, benzylic, and propargylic types were applicable. In addition, bulky OSitBuMe2 and OSiiPr3 groups, other than the OSiMe3 group, were successfully substituted. The substitution reaction of enantiopure secondary benzylic silyl ether yielded the corresponding racemic thioether product, which suggested that the reaction of tertiary alkyl, secondary alkyl, benzylic, and propargylic silyl ethers would proceed via a SN1 mechanism.

Coupling Reaction of Enol Derivatives with Silyl Ketene Acetals Catalyzed by Gallium Trihalides.

A cross-coupling reaction between enol derivatives and silyl ketene acetals catalyzed by GaBr3 took place to give the corresponding α-alkenyl esters. GaBr3 showed the most effective catalytic ability, whereas other metal salts such as BF3 ⋅OEt2 , AlCl3 , PdCl2 , and lanthanide triflates were not effective. Various types of enol ethers and vinyl carboxylates as enol derivatives are amenable to this coupling. The scope of the reaction with silyl ketene acetals was also broad. We successfully observed an alkylgallium intermediate by using NMR spectroscopy, suggesting a mechanism involving anti-carbogallation among GaBr3 , an enol derivative, and a silyl ketene acetal, followed by syn-ß-alkoxy elimination from the alkylgallium. Based on kinetic studies, the turnover-limiting step of the reaction using a vinyl ether and a vinyl carboxylate involved syn-ß-alkoxy elimination and anti-carbogallation, respectively. Therefore, the leaving group had a significant effect on the progress of the reaction. Theoretical calculations analysis suggest that the moderate Lewis acidity of gallium would contribute to a flexible conformational change of the alkylgallium intermediate and to the cleavage of the carbon-oxygen bond in the ß-alkoxy elimination process, which is the turnover-limiting step in the reaction between a vinyl ether and a silyl ketene acetal.

Gallium trihalide catalyzed sequential addition of two different carbon nucleophiles to esters by using silyl cyanide and ketene silyl acetals.

A sequential addition of silyl cyanide and ketene silyl acetals to esters was achieved by a gallium trihalide catalyst to produce ß-cyano-ß-siloxy esters. This is the first example of the sequential addition of two different carbon nucleophiles to esters. The employment of lactones provided α,α-disubstituted cyclic ethers with a cyano group and an ester moiety. A variety of esters and lactones are applicable to this reaction system.

Indium chloride catalyzed alkylative rearrangement of propargylic acetates using alkyl chlorides, alcohols, and acetates: facile synthesis of α-alkyl-α,ß-unsaturated carbonyl compounds.

Indium chloride catalyzed alkylative rearrangement of propargylic acetates into α-alkyl-α,ß-unsaturated carbonyl compounds has been achieved. Propargylic acetates functioned as α-acylvinyl anion equivalents to react with carbocations generated from alkyl chlorides. Other alkyl electrophiles such as alcohols and acetates were also applicable.

Zn(II) chloride-catalyzed direct coupling of various alkynes with acetals: facile and inexpensive access to functionalized propargyl ethers.

The coupling of acetals with various alkynes was achieved using only 1 mol% of inexpensive and mild Lewis acid ZnCl2, which furnished propargyl ethers. The coupling was catalyzed by Zn(OMe)Cl, which was generated in situ to form an alkynylzinc species. This protocol was allowed to expand to a one-pot subsequent reaction with allylchlorosilane to obtain a 1,4-enyne product.

Synthesis of alkylbismuths by regiodivergent carbobismuthination of simple alkenes.

Switchable regioselectivity: This study represents the first carbobismuthination of alkenes achieved by the treatment of an alkene with a bismuth halide and a ketene silyl acetal. This reaction is particularly noteworthy in that a change in the type of halogen on a bismuth atom very easily switched the regioselectivity.

Indium triiodide catalyzed reductive functionalization of amides via the single-stage treatment of hydrosilanes and organosilicon nucleophiles.

The indium triiodide catalyzed single-stage cascade reaction of N-sulfonyl amides with hydrosilanes and two types of organosilicon nucleophiles such as silyl cyanide and silyl enolates selectively promoted deoxygenative functionalization to give α-cyanoamines and ß-aminocarbonyl compounds, respectively.

Indium(III) halide-catalyzed UV-irradiated radical coupling of iodomethylphosphorus compounds with various organostannanes.

The first catalytic radical coupling of iodomethylphosphorus compounds was accomplished with allyl-, alkenyl-, and allenylstannanes under UV irradiation in the presence of an indium(III) halide catalyst, for which a transmetalated allylic indium species was confirmed to be an active radical species.

InCl3/Me3SiCl-catalyzed direct Michael addition of enol acetates to α,ß-unsaturated ketones.

The direct Michael addition of enol acetates to α,ß-unsaturated ketones was achieved using a combination of Lewis acid catalysts, InCl(3) and Me(3)SiCl, which furnished stable enol-form products that could be further transformed into functionalized 1,5-diketones by reactions with various electrophiles.

Lithium phenolates with a hexagonal-prismatic Li6O6 core isolated via a cage-shaped tripodal ligands system: crystal structures and their behavior in solution.

Stable hexanuclear lithium phenolate bearing a cage-shaped tripodal ligand was isolated, which had a hexagonal-prismatic Li(6)O(6) core at room temperature, because of the hard mobility of the ligand and its reduction of the problematic steric repulsion. The properties of the lithium phenolates were analyzed by X-ray crystallography and NMR spectroscopy.

Synthesis of a wide range of thioethers by indium triiodide catalyzed direct coupling between alkyl acetates and thiosilanes.

An indium triiodide-catalyzed substitution of the acetoxy group in alkyl acetates with thiosilanes provides access to a variety of thioethers. The method is efficient for a wide scope of acetates such as primary alkyl, secondary alkyl, tertiary alkyl, allylic, benzylic, and propargylic acetates.

Recognition of aromatic compounds by π pocket within a cage-shaped borate catalyst.

Taking shape: the ability of a Lewis acid catalyst to distinguish between aromatic and aliphatic hydrocarbon moieties was accomplished by using cage-shaped borate catalysts B(OC(6)H(3)Aryl)(3)CH having a π pocket derived from aryl substituents surrounding the boron center. The catalyst predominantly activated aromatic aldehydes over aliphatic ones for reaction.

Direct use of esters in the Mukaiyama aldol reaction: a powerful and convenient alternative to aldehydes.

An indium triiodide catalyst promoted the direct transformation from esters to ß-hydroxycarbonyl compounds using hydrosilanes and silyl enolates by a one-stage process. Various esters were applicable, and the high chemoselectivity of this system brings compatibility to many functional groups: alkenyl, alkynyl, chloro, and hydroxy.