Yoshihiro Nishimoto

Esters as acylating reagent in a Friedel-Crafts reaction: indium tribromide catalyzed acylation of arenes using dimethylchlorosilane.

The Friedel-Crafts acylation of arenes with esters by dimethylchlorosilane and 10 mol % of indium tribromide has been achieved. The key intermediate RCOOSi(Cl)Me(2) is generated from alkoxy esters with the evolution of the corresponding alkanes. The scope of the alkoxy ester moiety was wide: tert-butyl, benzyl, allyl, and isopropyl esters were successful. In addition, we demonstrated the direct synthesis of the indanone intermediate 11 of salviasperanol from ester 10.

Regio‐ and Stereoselective Generation of Alkenylindium Compounds from Indium Tribromide, Alkynes, and Ketene Silyl Acetals

InBr(3) promotes the addition of ketene silyl acetals to monosubstituted alkynes to afford 2,2-disubstituted alkenylindium compounds in high regio- and stereoselectivity (see scheme). In addition, the alkenylindium derivatives have been subsequently coupled with iodobenzene in the presence of a palladium catalyst.

Direct coupling of alcohols with alkenylsilanes catalyzed by indium trichloride or bismuth tribromide

Indium halides or bismuth halides catalyzed the coupling of various alcohols with alkenylsilanes to give the corresponding alkenes stereospecifically without any other activators.

α‐Alkylation of Carbonyl Compounds by Direct Addition of Alcohols to Enol Acetates

The catalytic a-alkylation of carbonyl compounds has contributed remarkably to the development of organic synthesis, and the reaction of enolate derivatives with alkyl electrophiles is a powerful alkylation method. Alcohols are appealing electrophiles, as they are plentiful and readily synthesized; however, the direct use of alcohols is effectively prevented by the fact that the hydroxy group is a particularly poor leaving group, and it often tends to decomposition of catalysts and active intermediates. The a-alkylation of monocarbonyl compounds using an alcohol remains problematic whereas many research groups have reported the direct alkylation of 1,3-dicarbonyl compounds. The transfer hydrogenation method has achieved some direct a-alkylations of ketones, although this is only applicable to primary alcohols and requires a strong base to generate the enolate species. Hidai, Uemura et al. published a ruthenium-catalyzed system, which was limited to the reactions of 1-arylpropargylic alcohols, in the presence of an excess of ketone. Methods using metal enolates suffer from decomposition of the enolates by the hydroxy group, critically narrowing the scope of available alcohol substrates; furthermore, the aalkylation of aldehydes has not been investigated to the degree that ketones have. Herein, we report a synthesis of aalkylated carbonyl compounds from enol acetates and alcohols, catalyzed by InI3, GaBr3, or FeBr3, in which the aalkylation of not only ketones but also of aldehydes has been successfully achieved. Furthermore, the exploitation of enol acetates as readily available, stable, and easily-handled enolate reagents enhances the practicality of this a-alkylation method. We employed Lewis acids to selectively activate alcohols and thereby suppress side reactions, such as transesterification. We recently found that the moderate Lewis acidity of indium trihalide effectively promoted the direct coupling of alcohols with nucleophiles, such as allyl and alkenyl silanes; these results suggested that indium trihalide selectively interacts with hydroxy groups in the presence of other oxygen-containing moieties such as carbonyl groups. As a model reaction, 1-phenylethanol (1a) and 2-propenyl acetate (2a) were heated to reflux in 1,2-dichloroethane in the presence of 5 mol% indium trihalide to afford the desired product 3aa in satisfactory yields, of which InI3 gave the highest (83 %; Table 1, entries 1–3). By contrast, the more

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.

InCl3/Me3SiBr-Catalyzed Direct Coupling between Silyl Ethers and Enol Acetates

A combined Lewis acid catalyst of InCl(3) and Me(3)SiBr promoted the direct use of enol acetates in the coupling with low-reactive silyl ethers, in which functional groups including ketones and aldehydes survived. Sterically hindered silyl ethers such as ROSiEt(3), ROSiPh(3), ROSit-BuMe(2), and ROSii-Pr(3) were also applicable.

Indium tribromide catalyzed cross-Claisen condensation between carboxylic acids and ketene silyl acetals using alkoxyhydrosilanes.

Carbon acylations play an important role in the construction of carbon frameworks having a carbonyl group. Among them, the Claisen condensation is one of the most useful methods, as it furnishes various b-ketoesters. A classical example is the homocondensation of esters promoted by a strong base. Recent successful developments in the cross-condensation between metal enolates and active acylating reagents, such as acid anhydrides or acid chlorides, have resulted in a reduction in side reactions. Carboxylic acids are promising candidates as acylating reagents, but their direct use remains a challenging problem because the acidic proton often causes decomposition of the catalyst and undesired side reactions. Most of the reported reactions require the use of harsh reagents such as SOCl2 [6] or N,N’-carbonyldiimidazole to prepare active intermediates from carboxylic acids, and these reactions result in troublesome by-products being generated. Recently, Tanabe and co-workers reported the cross-condensation of titanium and silyl enolates under mild reaction conditions, but the system also required an extra step to prepare active intermediates. Herein, we describe a convenient indium-catalyzed cross-Claisen condensation, in which the simple and sequential addition of a carboxylic acid, an alkoxyhydrosilane, and a ketene silyl acetal in the presence of InBr3 gives the desired product. Owing to its moderate Lewis acidity, high tolerance to an acidic proton, and compatibility with various functional groups, we recently focused on using indium trihalides to achieve a direct coupling reaction of alcohols with various nucleophiles and the Friedel–Crafts acylation using carboxylic acids. 9] These results prompted us to attempt the condensation reaction between benzoic acid 1a and dimethylketene methyltrimethylsilyl acetal (2a) in the presence of an indium trihalide. The use of a catalytic amount of InBr3 gave hardly any condensation product (Table 1, entry 1) and the addition of Me3SiCl was ineffective (Table 1, entry 2). Next, the use of Me2ClSiH, which was effective in the Friedel– Crafts acylation using carboxylic acids, furnished the desired product 3aa, but the yield was only 39 % despite a high reaction conversion (Table 1, entry 3). These results indicated that the combination of an indium halide and a silyl halide, which often acts as a strong Lewis acid, 10] is not applicable for this reaction. Gratifyingly, the employment of alkoxyhydrosilanes, instead of Me2ClSiH, accelerated the cross-Claisen condensation, which was accompanied by the vigorous generation of hydrogen gas; (MeO)3SiH gave the best result (Table 1, entries 4–6). This method has a clear advantage that the successive addition of all the reagents in the order of InBr3, 1a, hydrosilane, and 2 a gave high yields of 3aa, and a specific step for the generation of an active acylating reagent was not required. When Et3SiH was used a rapid evolution of hydrogen gas occurred, but the desired product was obtained in only 7% yield (Table 1, entry 7). The use of (MeO)3SiH in the absence of indium trihalide furnished no product (Table 1, entry 8). The combination of (MeO)3SiH with InI3 gave a satisfying result (Table 1, entry 9), while InCl3 and In(OTf)3 showed low activity (Table 1, entries 10 and 11). Direct acylations using a variety of carboxylic acids were examined under the optimized reaction conditions, which included InBr3 catalyst, and (MeO)3SiH (Table 2). Aromatic carboxylic acids bearing either electron-donating and electron-withdrawing groups reacted with ketene silyl acetals 2a to give the desired b-ketoesters 3 (Table 2, entries 1–3). Aliphatic carboxylic acids were also applicable except for the bulky pivalic acid (1 g ; Table 2, entries 4–6). A notable Table 1: Cross-Claisen condensation between benzoic acid (1a) with dimethylketene silyl acetal 2a.

Reaction of alcohols and silyl ethers in the presence of an indium/silicon-based catalyst system: Deoxygenation and allyl substitution

An In(III)/Si catalyst system effects the direct allyl substitution of alcohols and silyl ethers under mild conditions. A deoxygenation of alcohols is also promoted by InCl3 catalyst. This method requires no pretreatment or protection of hydroxy groups or deprotection of siloxy groups. The completion of the catalytic allylation depends on the low oxophilicity and high halophilicity of In(III) halide species, and other representative Lewis acids such as AlCl3 and BF3 have no catalytic activity for the allylations. The oxophilicity and halophilicity are also demonstrated by NMR studies.

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

Indium chloride catalyzed alkylative rearrangement of propargylic acetates into α-alkyl-α,β-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.

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 β-aminocarbonyl compounds, respectively.