Kimihiro Komeyama

Cationic iron-catalyzed intramolecular alkyne-hydroarylation with electron-deficient arenes

Fe(OTf)(3) effectively catalyzed intramolecular hydroarylation of aryl-substituted alkynes with electron-deficient arenes under mild conditions.

Highly Diastereoselective Iron‐Mediated C(sp2)C(sp3) Cross‐Coupling Reactions between Aryl Grignard Reagents and Cyclic Iodohydrine Derivatives

Transition-metal-catalyzed cross-coupling reactions have become indispensible tools for C C bond-forming reactions in modern organic synthesis. Most of these reactions depend on the use of palladium or nickel complexes as catalysts. Although these metals are used in only catalytic amounts, they have the disadvantage of being toxic and/or expensive. Iron-mediated coupling reactions were found to be a valuable alternative, since iron is one of the most abundant transition metals and its salts are inexpensive and environmentally benign. Despite spectacular advances and insights into the role of iron in coupling reactions, only a few stereoselective versions of iron-mediated or -catalyzed C(sp) cross-coupling reactions are known. 6f, 7] Recently, we developed a diastereoselective palladiumcatalyzed cross-coupling of various substituted cycloalkylzinc reagents with (hetero)aryl halides and bromoalkynes. However, this coupling reaction could not be used for the preparation of a-arylated cyclohexanol derivatives of type 1, since the required zinc reagent 2 undergoes fast elimination to give cyclohexene (3 ; Scheme 1). Products of type 1 are versatile building blocks for pharmaceuticals, chiral ligands, and auxiliaries. They are usually obtained by the opening of the corresponding epoxides with aryl organometallic compounds. Enantioselective versions of this opening are of limited scope. In fact, the most efficient procedures for the desymmetrization of oxacycles using aryl Grignard reagents have only been reported for oxabenzonorbornadienes and 2,3-disubstituted 7-oxabicyclo[2.2.1]hept-5-enes. These problems can be solved by an alternative retrosynthesis involving the diastereoselective coupling of the readily available iodohydrine derivative 4 with ArMgX 5 (Scheme 1). In preliminary experiments, we examined the crosscoupling of the TBS-protected (TBS = tert-butyldimethylsilyl) iodohydrine 4 with PhMgCl in the presence of various iron salts (Scheme 2). The addition of PhMgCl to the

Bismuth-catalyzed intramolecular carbo-oxycarbonylation of 3-alkynyl esters.

Borderline metal complexes, especially Bi(OTf)3, efficiently catalyze the carbo-oxycarbonylation of alkynyl esters to form multisubstituted lactones in moderate to high yields.

Intramolecular Alkynylcyclopropanation of Olefins Catalyzed by Bi(OTf)3: Stereoselective Synthesis of 1-Alkynyl-3-azabicyclo[3.1.0]hexanes†

The development of efficient cyclization methods for the construction of nitrogen-containing heterocycles constitutes an ongoing challenge in the construction of natural and pharmaceutical materials. The cycloisomerization of enynes is one such method, for which transition metal catalysts, such as palladium, platinum, gold, ruthenium, and rhodium, have been found to effectively promote the reaction. However, most of these procedures require high loading of expensive metal catalysts and ligands; moreover, accessible heterocyclic skeletons are limited. Therefore, the development of more practical catalyst systems for the synthesis of new heterocycles is desirable. To this end, we have recently reported the iron-catalyzed or bismuth-catalyzed intramolecular heterofunctionalization of olefins and alkynes; this provides various types of heterocycles in both an environmentally friendly and atom efficient manner. Nitrogen-containing heterocycles, such as 3-azabicyclo[3.1.0]hexanes, are core structures of a variety of biologically active compounds. Some efficient synthetic routes to this skeleton have been reported, which use stoichiometric quantities of organometallic reagents. Recently, catalytic approaches to 3-azabicyclo[3.1.0]hexanes, which contain a vinylcyclopropane motif, have been developed using the transition-metal-catalyzed tandem carbometalation of 1,6enynes with organotin or diazoalkane (Scheme 1). These vinylcyclopropane motifs are prized for their utility in ringexpansion reactions, affording a variety of heterocyclic ring sizes. In contrast, the synthesis of analogous azabicyclohexanes with alkynyl substituents have been scarcely reported, even though the alkynylcyclopropanes are versatile units for numerous chemical transformations and are substructures in many natural products. To construct the skeleton, we envisaged that propargyl alcohol might act as a synthetic equivalent of propargyl carbene A, which is a useful active species for the alkynylcyclopropanation of olefins (Scheme 2). It is known that propargyl alcohols undergo nucleophilic addition at the gposition in the presence of a Lewis acid to form allenyl

Tandem ene-reaction/hydroamination of amino-olefin and -allene compounds catalyzed by Bi(OTf)3

Bi(OTf)(3) was proven to act as an effective catalyst for tandem ene-reaction/hydroamination of amino-olefin and amino-allene compounds with some enophiles, giving rise to functionalized N-heterocycles in good yields.

Borderline metal-catalyzed carboarylation of alkynylarenes using N,O-acetals

Borderline metal catalysts, Bi(OTf)(3) and Fe(OTf)(3), were proven to work as dual activators for alkynes and N,O-acetals via σ,π-chelation, which achieved a new carboarylation reaction of alkynylarenes with N,O-acetals.

Direct mono-insertion of isocyanides into terminal alkynes catalyzed by rare-earth silylamides

Rare-earth silylamide complexes, Ln[N(SiMe3)2]3 (Ln = Y, La, Sm, Yb), effectively catalyzed the coupling reaction of isocyanides with both aliphatic and aromatic terminal alkynes under mild conditions.

NHC-catalyzed reaction of enals with unactivated enones: substituent effect on the formation of 1 : 1 and 1 : 2 adducts

It has been found for the first time that the imidazole carbene-catalyzed reaction of α,β-unsaturated aldehydes with unactivated enones gives two kinds of pyranones, 1 : 1 and 1 : 2 adducts, instead of cyclopentenes and cyclopentanones. The ratio of the two products was determined by the substituent effect of the enones, not by a molar ratio of the starting materials in general. Moreover, a longer reaction period caused the formation of another 1 : 2 adduct, which was derived from the 1 : 1 pyranones initially formed.

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

Thiazolium carbene-catalyzed reactions of 1,2-diketones and 1,2,3-triketones with enones and ynones have been investigated. The diketones gave α,β-double acylation products via unique Breslow intermediates isolable as acid salts, whereas the triketones formed stable adducts with the NHC instead of the coupling products.

Nickel and Nucleophilic Cobalt-Catalyzed Trideuteriomethylation of Aryl Halides Using Trideuteriomethyl p-Toluenesulfonate

Herein, a novel approach for the trideuteriomethylation of aryl halides using nickel and nucleophilic cobalt catalysts and the readily available trideuteriomethyl p-toluenesulfonate (CD3OTs) is described. This method provides access to a wide range of CD3-containing arenes. Moreover, a transmethylation step is revealed as crucial in the nickel/cobalt catalytic mechanism.