Kohei Endo

Efficient formation of ring structures utilizing multisite activation by indium catalysis.

Lewis acidic indium(III) salts, in particular In(NTf(2))(3), effect the conversion of alpha-(omega-alkynyl)-beta-ketoesters and omega-alkynyl-beta-ketoesters to the corresponding cyclic products in a manner known as the Conia-ene reaction. This reaction can lead to the creation of five- to fifteen-membered-ring carbocycles and heterocycles in good to excellent yields. The synthetic features of the reaction are a relatively low catalyst loading, as low as 0.01 mol % in the best case, as well as no requirement of solvent for five-membered-ring formation and the requirement of only moderately dilute reaction conditions for medium-sized-ring formation. The high reactivity of indium salts is due to the double activation of the beta-ketoester substrate containing an acetylene function. The indium metal activates the beta-ketoester moiety by the formation of an indium enolate, and this indium metal electrophilically activates the alkyne moiety. Such a strong push-pull activation of the substrate by a single metal circumvents the disadvantage of entropic and enthalpic factors generally associated with the formation of medium- and large-sized rings. The reaction allows the ready formation of a fifteen-membered-ring carbocycle, from which dl-muscone has been synthesized.

Chemoselective Suzuki Coupling of Diborylmethane for Facile Synthesis of Benzylboronates

The chemoselective Pd-catalyzed Suzuki-Miyaura cross-coupling reaction using a diborylmethane is reported. The use of an equimolar amount of base with a diborylmethane realized chemoselective coupling for the synthesis of various benzylboronate derivatives. Sterically hindered aryl bromides can give products in moderate to excellent yields.

Cross Coupling between sp3-Carbon and sp3-Carbon Using a Diborylmethane Derivative at Room Temperature

A novel example of the Suzuki-Miyaura cross-coupling reaction between sp(3)-carbon and sp(3)-carbon is described. The reaction of a diborylmethane derivative with allyl halides or benzyl halides proceeded efficiently in the presence of appropriate Pd-catalysts at room temperature. The present approaches provide functionalized homoallylboronates and alkylboronates with excellent regio- and chemoselectivities.

Construction of a Chiral Quaternary Carbon Center by Indium-Catalyzed Asymmetric α-Alkenylation of β-Ketoesters

Construction of a nonracemic all-carbon quaternary stereocenter at the alpha-position of beta-ketoesters was achieved by way of an indium(III)-catalyzed diastereoselective alpha-alkenylation reaction of chiral enamines with 1-alkynes. The enamine bearing a chiral auxiliary derived from l-isoleucine was added to the alkyne to give an alpha-alkenylated product in excellent yield and with a stereoselectivity better than 90% ee. One can ascribe the high selectivity to a chelate intermediate involving the auxiliary and the metal atom and the high yield to efficient interactions between the indium(III) atom and the alkyne. The selectivity increased as the reaction temperature was raised to 120 degrees C and decreased at higher temperatures.

One-pot synthesis of symmetrical and unsymmetrical diarylmethanes via diborylmethane.

A one-pot synthesis of diarylmethanes from air-stable diborylmethane via the Suzuki-Miyaura cross-coupling reaction is described. The present approach realizes the synthesis of various symmetrical and unsymmetrical diarylmethanes in good to excellent yields.

Effect of multinuclear copper/aluminum complexes in highly asymmetric conjugate addition of trimethylaluminum to acyclic enones.

Al and friends: asymmetric conjugate addition of Me(3)Al to β,β-disubstituted α,β-unsaturated ketones in the presence copper and L1 leads to a highly efficient construction of an all-carbon-substituted chiral quaternary center. This result is the first example of an asymmetric conjugate addition of Me(3)Al to acyclic enones to give a chiral quaternary carbon center with excellent yield and enantioselectivity under mild reaction conditions.

Enantioselective synthesis of chiral tripodal cage compounds by [2 + 2 + 2] cycloaddition of branched triynes

Cyclotrimerization of triynes branched by a nitrogen atom of 2-aminophenol yielded planar-chiral tripodal cage compounds. When a cationic Rh-Me-DUPHOS catalyst was used, the cycloadducts were obtained in high yield and excellent ee, and a macrocyclic compound with a [15]cyclophane system was also obtained. This method can be further applied to the synthesis of a triarmed pyridinophane by the intramolecular reaction of a diyne-nitrile.

Stereoselective synthesis of trisubstituted E-iodoalkenes by indium-catalyzed syn-addition of 1,3-dicarbonyl compounds to 1-iodoalkynes.

Indium-catalyzed addition of 1,3-dicarbonyl compounds to 1-iodo-1-alkynes takes place exclusively in a syn-fashion to produce E-iodoalkenes. The iodine atom serves both as an activating group and as a group that controls the regioselectivity of the addition. The E-alkenyl iodide product can be further derivatized using either a one-pot or a two-pot procedure into trisubstituted olefins in high overall yield with retention of the stereochemistry.

Enantioselective synthesis of planar-chiral 1,n-dioxa[n]paracyclophanes via catalytic asymmetric ortho-lithiation.

Highly enantioselective ortho-lithiation and dilithiation of 1,n-dioxa[n]paracyclophanes were realized with the use of sec-butyllithium and a catalytic or stoichiometric amount of sparteine. Quenching with various electrophiles, such as iodine, iodomethane, and chlorodiphenylphosphine, afforded chiral mono- and disubstituted paracyclophanes with good to excellent ee.

Multinuclear Cu-catalysts based on SPINOL-PHOS in asymmetric conjugate addition of organozinc reagents.

Multinuclear Cu/Zn complex-catalyzed efficient asymmetric conjugate addition of organozinc reagents to acyclic and cyclic enones has been developed in the presence of a wide variety of regioisomeric chiral diols bearing phosphorus moieties as ligands. The regioisomeric SPINOL-PHOS ligands based on a SPINOL architecture showed an unexpected inversion of stereoselectivity.