Atsushi Kawata

Manganese‐Catalyzed Cleavage of a Carbon–Carbon Single Bond between Carbonyl Carbon and α‐Carbon Atoms of Ketones

Olefin metathesis, which proceeds through a carbon–carbon (C C) double bond cleavage, is a well-known and useful method in synthetic organic chemistry. In contrast, cleavage of a C C single bond is still one of the most difficult and challenging reactions in organic synthesis. Recently, there have been several reports on transition-metal-catalyzed transformations. For example, reactions of strained molecules, such as threeand four-membered rings, have been reported. In these reactions, release of the ring strain is the driving force for C C single bond cleavage. As for reactions not involving ring strain, transformations using a directing group, cleavage of a carbon–nitrile bond, and transformations by retro-reactions, including retro-allylations, retroarylations, retro-alkynylation, retro-aldol reactions, 10] and deallylation are also well known. To promote C C single bond cleavage, we employed a manganese catalyst and carbodiimides. We report herein the cleavage of a unstrained C C single bond between the carbonyl carbon and a-carbon atoms of ketones, and its application to the synthesis of amides. Treatment of propiophenone (1 a) with 1.0 equivalent of 1,3-di-p-tolylcarbodiimide (2a) in the presence of a catalytic amount of a manganese complex, [Mn2(CO)10], in 1,4-dioxane at 150 8C for 24 hours gave amide 3a in 50% yield. This reaction also proceeds using either the iron complex [Fe2(CO)9] or the cobalt complex [Co2(CO)8] as a catalyst. [15]

Rhenium-Catalyzed Synthesis of Multisubstituted Aromatic Compounds via C−C Single-Bond Cleavage

A reaction between a beta-keto ester and an acetylene in the presence of a rhenium complex, [ReBr(CO)3(thf)]2, as a catalyst, provided a 2-pyranone derivative in excellent yield via retro-aldol reaction (C-C single bond cleavage). By adding an acetylene-bearing ester group(s) after the formation of 2-pyranones, an aromatization reaction proceeded and multisubstituted aromatic compounds were obtained in good to excellent yields.

Rhenium- and Manganese-Catalyzed Insertion of Alkynes into a Carbon–Carbon Single Bond of Cyclic and Acyclic 1,3-Dicarbonyl Compounds

Treatment of alkynes with cyclic and acyclic 1,3-dicarbonyl compounds in the presence of a catalytic amount of a rhenium or manganese complex gives ring-expanded and carbon-chain extension products, respectively. In these reactions, alkynes insert into a non-strained carbon-carbon single bond of 1,3-dicarbonyl compounds. The ring-expansion reaction is also promoted by the addition of 4-A molecular sieves instead of a catalytic amount of an isocyanide.

Rhenium- and Manganese-Catalyzed Synthesis of Aromatic Compounds from 1,3-Dicarbonyl Compounds and Alkynes

We have succeeded in the development of three approaches to the synthesis of aromatic compounds from 1,3-dicarbonyl compounds and alkynes. The first approach is a manganese-catalyzed [2+2+2] cycloaddition between 1,3-dicarbonyl compounds, which have no substituents at the active methylene moiety, and terminal alkynes. This reaction proceeds with high regioselectivity when aryl acetylenes are employed as the alkyne component. The second approach is a rhenium- or manganese-catalyzed formal [2+1+2+1] cycloaddition between beta-keto esters and two kinds of alkynes. In this reaction, the aromatic compounds are obtained by the following reaction sequence: (1) insertion of the first alkyne into a carbon-carbon single bond of a beta-keto ester, (2) formation of 2-pyranones via intramolecular cyclization with the elimination of ethanol, and (3) Diels-Alder reaction between the formed 2-pyranone and the second alkyne. This reaction provides multisubstituted aromatic compounds in a regioselective manner. The third approach is a rhenium-catalyzed formal [2+2+1+1] cycloaddition reaction from two 1,3-diketones and one alkyne. In this reaction, the aromatic skeleton is constructed from three carbons of the first 1,3-diketone, two carbons of the alkyne, and one carbon of the second 1,3-diketone.

Rhenium-Catalyzed Formation of Bicyclo[3.3.1]nonene Frameworks by a Reaction of Cyclic β-Keto Esters with Terminal Alkynes

Treatment of cyclic beta-keto esters with terminal alkynes in the presence of a catalytic amount of a rhenium complex, [ReBr(CO)(3)(thf)](2), gave bicyclo[3.3.1]nonene derivatives. The reaction conditions and yields of the bicyclo[3.3.1]nonenes were improved by the sequential use of tetrabutylammonium fluoride (TBAF) after the rhenium-catalyzed reactions.

Rhenium-catalyzed synthesis of indene derivatives via C-H bond activation

Rhenium complex, [ReBr(CO)3(thf)]2-catalyzed reactions between aromatic imines and either acetylenes or α,β-unsaturated carbonyl compounds gave indene derivatives in good to excellent yields. These reactions proceed via C-H bond activation, insertion of acetylenes or α,β-unsaturated carbonyl compounds, intramolecular nucleophilic cyclization, and reductive elimination. Indene derivatives were also obtained from aromatic ketones and α,β-unsaturated carbonyl compounds in the presence of catalytic amounts of the rhenium complex and p-anisidine. Sequential ruthenium-catalyzed hydroamination of aromatic acetylenes with anilines, and rhenium-catalyzed reactions of the formed aromatic ketimines with α,β-unsaturated carbonyl compounds also provided indene derivatives.

Indium‐Catalyzed Synthesis of Keto Esters from Cyclic 1,3‐Diketones and Alcohols and Application to the Synthesis of Seratrodast

Esterification reactions from cyclic 1,3-diketones and alcohols are carried out in the presence of several Lewis acids. In particular, indium(III) triflate, In(OTf)(3), iron(III) triflate, Fe(OTf)(3), copper(II) triflate, Cu(OTf)(2), and silver(I) triflate, AgOTf, show high catalytic activities. These reactions proceed through the carbon-carbon bond cleavage by a retro-aldol reaction and were found to be highly regioselective even in the presence of other functional groups. This type of reaction can also be applied to the preparation of the keto esters during the synthesis of seratrodast, which is an antiasthmatic and eicosanoid antagonist.

Rhenium- and manganese-catalyzed carbon-carbon bond formation using 1,3-dicarbonyl compounds and alkynes*

A rhenium complex, [ReBr(CO)3(thf)]2, catalyzed insertion of terminal alkynes into a C–H bond of active methylene sites of 1,3-dicarbonyl compounds. When a catalytic amount of isocyanide or molecular sieves was added to the reaction mixture, the reaction course changed markedly, and insertion of alkynes into a C–C single bond between α- and β-positions of cyclic and acyclic β-keto esters occurred. The formed acyclic δ-keto esters could be converted to 2-pyranones, which were applied to the synthesis of multisubstituted aromatic compounds via the Diels–Alder reaction and successive elimination of carbon dioxide. In the case of the rhenium-catalyzed reactions between terminal alkynes and β-keto esters without substituent at the α-position, tetrasubstituted benzenes were produced regioselectively by two-to-one reaction of the components. The yields of tetrasubstituted benzenes were improved by using a manganese catalyst.