下垣 実央

Three contiguous stereocenters were constructed by an amino acid-catalyzed asymmetric aldol reaction of α-siloxyketones with racemizable α-haloaldehydes via dynamic kinetic resolution. One-pot catalytic asymmetric synthesis of the highly functionalized products...

Chiral tandem modifiers linking two or three cinchonidine molecules at the 2′-position of the quinoline ring are highly effective at low concentrations for the enantioselective hydrogenation of PCA over Pd/C.

An oxetane intermediate during a direct aldol reaction was trapped with an internal aryl group to yield trans-tetraline products. The contribution of the oxetane intermediate was confirmed by 18O-isotope labeling experiments.

Ketone-based brominating agents (KBA), orthosubstituted 2,2,2-tribromoacetophenones, have been developed, and the highly enantioselective and practical alpha-bromination of aldehydes with KBA was achieved. The reaction could be performed in the presence of only 0.1-1 mol % of catalyst without using a halogenated solvent at 0 degrees C and was found to be scalable.

An efficient route to synthesize monosaccharide analogues in an enantio- and diastereoselective manner is described. Three contiguous stereocenters can be constructed via enantioselective benzoyloxylation of aldehydes using a chiral secondary amine catalyst and a subsequent aldol reaction of the resulting alpha-benzoyloxyaldehydes with the protected dihydroxyacetones using chiral amino acid catalysts, and single diastereomers were obtained with excellent enantioselectivity.

An efficient synthesis of novel chiral tritylpyrrolidine derivatives has been developed. Single stereoisomers of various tritylpyrrolidine derivatives can be readily obtained through diastereomer separation by simple silica gel column chromatography. Representative compounds of this class have been shown to be efficient amine organocatalysts for asymmetric benzoyloxylation.

The oxidation of (S-acyloxypent-3-enyebenzene with hypervalent iodine(III) afforded 2-oxy-1(oxymethyl)tetrahydronaphthalene under metal-free conditions. The acyloxy group may nucleophilically participate in the oxidative cyclization. A lactate-based chiral hypervalent iodine afforded an enantioselective variant of oxyarylation with up to 89% ee.

The enantioselective oxyarylation of (E)-6-aryl-1-silyloxylhex-3-ene was achieved using a lactate-based chiral hypervalent iodine(III) reagent in the presence of boron trifluoride diethyl etherate. The silyl ether promotes the oxidative cyclization, and enhances the enantioselectivity. In addition, the corresponding aminoarylation was achieved.

Stereoselective formation of substituted 1,3-dioxolanes was achieved through an assembly of three components: alkene, carboxylic acid and silyl enol ether. The reaction proceeded via stereospecific generation of a 1,3-dioxolan-2-yl cation intermediate during oxidation of alkene substrates with hypervalent iodine. The stereoselective trapping of the cation intermediate with silyl enol ether completed the formation of the dioxolane product.

In this study, the enantioselective oxylactonization of orthoalk-1-enylbenzoates with chiral hypervalent iodine(III) reagents yielded 3-alkyl-4-hydroxyisochroman-1-ones with high enantiomeric purity (ca. 90% ee). The enantioselective oxidation was also performed under catalytic conditions, in which a catalytic amount (10 mol-%) of a chiral iodoarene was oxidized to the hypervalent iodine species in situ using a stoichiometric co-oxidant, m-chloroperbenzoic acid (mCPBA). The catalytic oxidation mediated by chiral hypervalent iodine(III) species yielded enantiocontrolled syn products, while the direct oxidation of the substrate with mCPBA occurred as background oxidation to give racemic anti products. Under optimized conditions, the catalytic oxylactonization led to high levels of enantioselectivity (ca. 90% ee) and improved syn/anti selectivities (ca. 80% syn). The product distribution indicated that the lactate side-chain on the chiral iodoarene precatalyst plays an important role in enhancing both the enantioselectivity and the catalytic efficiency in the oxylactonization.

The first total syntheses of (12R)- and (12S)-12-hydroxymonocerins are described. The oxolane-fused isochroman-1-one framework is stereoselectively constructed via a double oxy-cyclization using a lactate-based chiral hypervalent iodine reagent. A catalytic variant of the double oxy-cyclization is also demonstrated using a chiral iodoarene as the precatalyst and m-CPBA as the co-oxidant.

Stereoselective oxylactonization of ortho-alkenylbenzoate with chiral hypervalent iodine is applied to the asymmetric synthesis of 4-oxyisochroman-1-one polyketide metabolites including 4-hydroxymellein (1), a derivative of fusarentin 2, monocerin (3), and an epimer of monocerin epi-3.