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In connection with our synthetic study toward the dimeric pyranonaphthoquinone antibiotics, actinorhodin (1) and β-naphthocyclinone (3), we describe herein the synthesis of a monomer, hemi-actinorh...

Substrate scope of the thiolate-mediated reductive cyclization of keto-enones was studied, revealing the applicability and novel mechanistic insights.

Previously we developed a promising synthetic approach to complex polycyclic natural products, including aromatic polyketides derived from the type-II polyketide biosynthesis. The approach consists of three key steps; (1) cycloaddition or cyclocondensation of nitrile oxide for assembling the carbon skeleton having an isoxazole as a 1,3-diketone equivalent, (2) benzoin cyclization for stereoselective ring fusion with an angular hydroxy group, and (3) oxidation of isoxazolium salt for installing an additional angular hydroxy group in stereoselective manner. As a synthetic exercise to highlight the utility of this approach, the first total syntheses of the proposed structure of pleospdione (1) and its C3-epimer (3-epi-1) have been achieved. The synthesis has proved the efficiency of the strategy as an entry into polyketide-derived complex architectures. At the same time, it was revealed that neither 1 nor 3-epi-1 represent the true structure of the natural product by incongruity of the NMR spectra.

By the action of chlorinating agent in the presence of alcohol, α-alkoxybenzocyclobutenone oximes are converted to stable benzonitrile oxides with an o-acetal moiety via facile ring-opening reaction.

Various multisubstituted benzenes were synthesized in highly chemo- and regioselective manners via nucleophilic aromatic substitution and ortho-metalation from 1,3,5-trifluorobenzene.

Diastereoselective vinylogous aldol reaction is reported by exploiting a silylated dioxinone to give anti-adducts in high selectivity.

A facile method for synthesizing trans-disubstituted cyclopropanes is described. γ,γ-Dimethyl homoallyl alcohols, upon conversion to the corresponding triflate, undergo smooth cyclization to give cyclopropanes in a stereoselective manner (trans) and in a stereospecific manner (inversion of configuration at the chiral center). Various functionalities could be introduced at the α-position of the newly formed cyclopropane ring by treating the cyclization mixture with hetero as well as carbon nucleophiles. Alternatively, treatment of the reaction mixture with triethylamine effects the clean elimination of a triflic acid to give high yields of the cyclopropanes with a 2-propenyl group, which are convertible to the corresponding cyclopropyl methyl ketones by ozonolysis in high yields. Also described is an application of the method to a short-step synthesis of a cyclopropane-containing eicosanoid, related to marine prostanoid biosynthesis.

Facile construction of azaspiro[4.5]decane skeletons was enabled by the ring expansion of benzocyclobutenols substituted with a pyridyl group, triggered by electrophilic activation of the heteroaro...

Stereocontrolled synthesis of (−)-afzelechin was achieved via the Mitsunobu reaction, where complete stereospecificity was observed when an electron-withdrawing group was introduced to the para-pos...

Organoaluminum reagents catalyze the addition of ketene silyl acetals to esters, affording the β-keto ester derivatives in good to excellent yields.

The first total synthesis of (±)-γ-indomycinone (2) has been accomplished starting from juglone (5) in nine steps, including Diels–Alder reaction of 5 and diene 6 and the formal 6-endo-dig cyclizat...

Various functionalized cyclooctadienones are accessible in high yields by the reaction of cyclobutenones with dienyllithium.

Dienylbenzocyclobutenes, readily available by the cycloaddition of benzyne and ketene silyl actetal followed by addition of dienyllithium, underwent thermal four-carbon ring expansion to give benzocyclooctenone derivatives in high yields. In some cases, acid treatment of the thermal product gave tricyclic ketones via transannular bond formation.

Hydrozirconation of allenyl sulfide generates a γ-thio-allylzirconocene species, which reacts with aldehydes and ketones to give anti olefinic β-sulfenyl alcohols in highly regio- and stereoselective manner.

An efficient two-step access to C-glycosyl juglones, promising synthetic intermediates toward aryl C-glycoside antibiotics, has been developed based on (1) the O → C-glycoside rearrangement and (2) the regioselective cycloaddition of α-alkoxybenzyne and α-oxyfuran.

Optically active alcohols possessing the R-configuration are produced in good optical yields by treating aromatic and aliphatic aldehydes with dialkylmagnesium by using the lithium salt of (2S, 2′S)-2-hydroxymethyl-1-[(1-methylpyrrolidin-2-yl)methyl]pyrrolidine as a chiral ligand.

Stereoselective cyclization of (Z)-(2R,3R,4R)-6-cyclohexyloxy-1,3,4-tribenzyloxy-5-hexen-2-ol (1)promoted by Hg(OCOCF3)2, followed by reductive work up gave the 2-deoxy-α-hexopyranoside derivative almost exclusively. On the other hand, a predominant formation of the β-anomer was achieved by the treatment of 1 with PhSeCl, and the successive deselenation.

Catalytic asymmetric addition of thiols to 2-cycloalkenone was studied by using the chiral amino alcohols, derived from L-hydroxyproline or (S)-proline, as base catalysts. Detailed investigation was carried out on the effects of the structure of the catalyst, the reaction medium, the temperature, and the concentration on the enantioselectivity. Good optical yields (47–88%) were achieved by the reaction of arenethiols and 2-cyclohexen-1-one in toluene at −5 °C, by using the catalyst (2S, 4S)-2-anilinomethyl-1-ethyl-4-hydroxypyrrolidine.

First total synthesis of mycinolide IV (2) was accomplished. Novel rearrangement of epoxyalcohol derivatives was applied to the synthesis of the C(11)–C(17) portion, assembly of which with the C(1)–C(10) portion (prepared via pinacol-type rearrangement) enabled a simple and stereoselective synthesis of 2

A convergent formal total synthesis of Polyoxin J was achieved. Two fragments, deoxypolyoxin C and 5-O-carbamoylpolyoxamic acid, were synthesized in a highly stereoselective manner from the common chiral building block, 4-O-benzyl-2,3-O-isopropylidene-L-threose, finishing the formal synthesis of Polyoxin J.

The visible and ultraviolet absorption spectra of the p-phenylenediamine cation (PD+), the N,N-dimethyl-p-phenylenediamine cation (DMPD+), and the N,N,N′,N′-tetramethyl-p-phenylenediamine cation (TMPD+) in the presence and in the absence of an excess counter anion (X−=Br−, Cl−, and ClO4−) are studied at low temperatures. Analyses of the data show that these cation radicals are in an equilibrium represented by 2R++X−\ightleftharpoonsR++2X− (or, more exactly, 2R++0.7X−\ightleftharpoonsR++2(X−)0.7). It is found that the absorption maxima of the dimer and the value of the heat of dimerization are independent of the kind of counter anion. It is concluded that PD+ and DMPD+ form strong dimers (heat of dimerization, ΔH=−8.0 and −8.2 kcal/mol respectively) and that TMPD+ forms a relatively weak one (ΔH=−5.6 kcal/mol). The features of the dimer spectra reflect the strength of the interaction of the radical in the dimer. In a strong dimer, the spectrum in the low-frequency region consists of a strong intermolecular...

In the presence of zinc halide, 2-furyllithium reacts with 2,3-O-isopropylidene-D-glyceraldehyde in a highly stereoselective manner to give the chiral and stereo-defined alcohol, 2,2-dimethyl-4-(2-furyl)hydroxymethyl-1,3-dioxolane, which is further elaborated to afford D-ribulose in three steps.

Optically active 3-arylthiocyclohexanones are produced in good optical yields by treating 2-cyclohexenone with aryl thiols in the presence of (2S,4S)-2-(anilinomethyl)-1-ethyl-4-hydroxypyrrolidine as a chiral catalyst.

(R)-3-(p-t-Butylphenylthio)cyclohexan-1-one was reduced with LiAlH(OBut)3 to afford (1S,3R)-3-(p-t-butylphenylthio)cyclohexan-1-o1, while the same reduction with LiBH(s-Bu)3 afforded the (1R,3R) counterpart almost exclusively. Elaboration of each product furnished both enantiomers of optically pure cyclohexenol derivatives.

4-O-Benzyl-2,3-O-isopropylidene-L-threose (1), a new building block for the synthesis of carbohydrates was prepared. The stereoselective addition of various nucleophiles to 1 afforded useful intermediates toward L-sugar derivatives.

Various optically active acetylenic alcohols (40-80%e.e.) were obtained by enantioface-differentiating addition of lithium trimethylsilylacetylide to aliphatic aldehydes utilizing (2S, 2′S)-2-hydroxymethyl-1-[(1-methylpyrrolidin-2-yl)methyl]pyrrolidine as a chiral ligand. Optically active (R)-1-trimethylsilyl-l-undecyn-3-ol (80%e.e.) was transformed into optically active 5-octyl-2(5H)-furanone in good yield.

Enantioselective addition of acetylene to aldehyde was investigated by the use of (2S, 2′S)-2-hydroxymethyl-1-[(1-methylpyrrolidin-2-yl)methyl]pyrrolidine as a chiral ligand. The addition of lithium trimethylsilylacetylide to benzaldehyde afforded the corresponding alkynyl alcohol in 92% optical yield.